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During a step-change in exercise power output (PO), ventilation ([Formula: see text]) increases with a similar time course to the rate of carbon dioxide delivery to the lungs ([Formula: see text]). To test the strength of this coupling, we compared [Formula: see text] and [Formula: see text] kinetics from ten independent exercise transitions performed within the moderate-intensity domain. Thirteen males completed 3-5 repetitions of ∆40 W step transitions initiated from 20, 40, 60, 80, 100, and 120 W on a cycle ergometer. Preceding the ∆40 W step transitions from 60, 80, 100, and 120 W was a 6 min bout of 20 W cycling from which the transitions of variable ∆PO were examined. Gas exchange ([Formula: see text] and oxygen uptake, [Formula: see text]) and [Formula: see text] were measured by mass spectrometry and volume turbine. The kinetics of the responses were characterized by the time constant (τ) and amplitude (Δ[Formula: see text]/Δ[Formula: see text]). Overall, [Formula: see text] kinetics were consistently slower than [Formula: see text] kinetics (by ~ 45%) and τ[Formula: see text] rose progressively with increasing baseline PO and with heightened ∆PO from a common baseline. Compared to τ[Formula: see text], τ[Formula: see text] was on average slightly greater (by ~ 4 s). Repeated-measures analysis of variance revealed that there was no interaction between τ[Formula: see text] and τ[Formula: see text] in either the variable baseline (p = 0.49) and constant baseline (p = 0.56) conditions indicating that each changed in unison. Additionally, for Δ[Formula: see text]/Δ[Formula: see text], there was no effect of either variable baseline PO (p = 0.05) or increasing ΔPO (p = 0.16). These data provide further evidence that, within the moderate-intensity domain, both the temporal- and amplitude-based characteristics of V̇

This case series aims to highlight that although extremely rare, osteoma can arise from the middle turbinate. We discuss the condition and treatment options. We describe 2 cases of osteomas arising from the middle turbinate. One occurring in a 29-year-old gentleman who presented to the ENT clinic with left nasal obstruction, and the other in a 65-year-old lady admitted to hospital with headaches and hypotension. Both cases were further investigated with CT scan. Both patients were treated with endoscopic fusion navigation assisted excision. Due to the large size of the mass, the gentleman required the mass to be delivered after it was drilled through and requiring septal deflection and vomerine spur reduction. As for the lady, the mass also required drilling and a posterior septotomy to facilitate dissection and removal of the tumour. Both patients made good recoveries with resolution of symptoms. Although extremely rare, osteomas can arise from the middle turbinate causing symptoms such as headache, facial pain, nasal obstruction and visual problems. As they are slow growing, they can be of large size at presentation. Treatment usually involves surgical excision. Endoscopic excision is usually adequate and safe.

Background:Remission is the stated goal for both patient and care-giver (1), but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a frame-work for such a definition (2), but without making a final recommendation.Objectives:To achieve consensus around a definition of remission in SLE (DORIS).Methods:The DORIS task force met annually from 2015 to 2020 and consisted of patient representatives and specialists in rheumatology, nephrology, dermatology, and clinical immunology. Systemic literature reviews of several key topics were done and specific research questions were examined in suitably chosen datasets. The findings were discussed, reformulated as recommendations, and voted upon. Level of evidence (LoE), strength of recommendation (SoR), and agreement were determined in standard fashion. The final recommendation for the DORIS definition of remission was established by electronic vote after finalization of the minutes of the most recent task force meeting.Results:Based on data from the literature and from several SLE-specific data sets, five key recommendations were endorsed (Table 1) that should be seen as additions to those published previously (2). Literature reviews identified strong support for the face-, content-, construct- and criterion validity of the definition based on the clinical SLEDAI (not including anti-DNA and complement) equal to zero plus low physician global assessment and allowing stable medical treatment. Thus, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical SLEDAI = 0, evaluator’s global assessment Table 1.Vote in favorLoESoRAgreement1.Inclusion of serology [anti-DNA, complement] in the DORIS definition of remission-on-treatment does not meaningfully alter the construct validity and therefore it is not recommended to include it90%2aB8.382.While the goal of treatment is sustained remission, a definition of remission should be able to be met at any point in time; therefore, duration should not be included in the definition100%5C9.023.To date, the SLEDAI-based definitions of remission have formally been investigated more extensively than BILAG-or ECLAM-based definitions. The SLEDAI-based definitions can therefore more confidently be recommended91%2aB9.254.Remission off treatment, while the ultimate goal for many patients and providers, is achieved very rarely. In clinical research and as an outcome in clinical trials, the definition for remission-on-treatment is recommended92%2aB9.525.In clinical trials, the LLDAS definition for low disease activity and the DORIS definition of remission are both recommended as outcomes100%5C9.25The 2021 DORIS definition of remission in SLE:Conclusion:The 2021 DORIS definition of remission in SLE was established. It is recommended for use as an aspirational treatment target in clinical care, a clear concept in education, and a key outcome in research including clinical trials and observational studies.References:[1]van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 2014;73:958-67.[2]van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis 2016.Disclosure of Interests:Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, Vielabo, Grant/research support from: BMS, GSK, Lilly, UCB, George Bertsias: None declared, Andrea Doria: None declared, David Isenberg: None declared, Eric F. Morand: None declared, Michelle A Petri: None declared, Bernardo Pons-Estel Consultant of: GSK, Janssen, Anisur Rahman: None declared, Manuel Ugarte-Gil Grant/research support from: Janssen, Pfizer, Alexandre Voskuyl: None declared, Laurent Arnaud Consultant of: Alexion, Amgen, Astra-Zeneca, BMS, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Medac, Novartis, Pfizer, Roche-Chugaï, UCB., Ian N. Bruce: None declared, Ricard Cervera Consultant of: GSK, Alexion, Eli Lilly, Astra Zeneca, Termo-Fisher, Rubió, Nathalie Costedoat-Chalumeau: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi, UCB, Frederic Houssiau: None declared, Marta Mosca: None declared, Matthias Schneider: None declared, Michael Ward: None declared, Cynthia Aranow: None declared.

Background The potential of TNFi or NSAIDs to reduce radiographic progression in AS is uncertain and causal effects of both exposures on radiographic progression have not been convincingly demonstrated. In addition, no study has evaluated whether effects are comparable among different NSAIDs in this setting. Objectives The objective of this study was to explore causal effects of NSAIDs and TNFi on radiographic progression in Ankylosing Spondylitis (AS) and to compare effects of celecoxib to other NSAIDs. Methods We included all patients meeting the modified New York criteria in a prospective cohort with at least 4 years of clinical and radiographic follow up. Clinical and medication data were collected every 6 months and radiographs were performed at baseline and every 2 years. We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of TNFi and NSAIDs (using the NSAID index) on radiographic progression as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at 2 and 4 years, accounting for time-varying covariates. We controlled for sex, race/ethnicity, education, symptom duration, enrollment year, number of years on TNFi, symptom duration at time of TNFi start, baseline mSASSS, ASDAS-CRP, current smoking, and missed visit status. Results Of the 519 patients, 75% were male with a baseline mean (SD) age and symptom duration of 41.4 (13.2) and 16.8 (12.5) years respectively. The baseline mean (SD) mSASSS was 14.2 (19.6). At baseline, NSAIDs were used in 66% of patients, of which ½ used an index Conclusions Dose related use of NSAIDs together with TNFi in AS patients has a synergistic effect in slowing radiographic progression with the greatest effect in those using both high-dose NSAIDs and TNFi. Celecoxib appears to confer the greatest benefit in decreasing progression with effect at both 2 and 4 years. Disclosure of Interest L. Gensler Grant/research support from: Amgen, AbbVie, UCB, Consultant for: Janssen, Lilly, Novartis, M. Gianfrancesco: None declared, M. Weisman Consultant for: Celltrion, Baylx, Novartis, Lilly, GSK, M. Brown Grant/research support from: Abbvie, Janssen, UCB, Leo Pharma, Consultant for: Abbvie, Janssen, Pfizer, Speakers bureau: Abbvie, UCB, Pfizer, M. Lee: None declared, T. Learch: None declared, M. Rahbar: None declared, J. Reveille Grant/research support from: Lilly UCB, Consultant for: Novartis Janssen Lilly UCB, M. Ward: None declared

The patient global assessment (PGA) occupies a central place among measures of rheumatoid arthritis (RA). Not only is the PGA one of the core measures in the American College of Rheumatology (ACR) response criteria, but it is the only patient-reported measure included in composite RA activity measures and in new criteria for remission. The PGA is an attractive measure because it is intended to capture, in a single item, an overall summary of the impact of RA on a patient's well-being. .However, its loosely-defined nature may contribute to wide variation among patients in the aspects of RA that are emphasized in marking the PGA, and which may be influenced by mood or other psychological factors. In several cross-sectional analyses, pain severity was the dominant influence on the PGA, accounting for up to 75% of inter-patient variation in ratings (1–7). Physical functioning, fatigue, depression, and in some studies, joint counts, were also important. The relative contribution of these features is difficult to assess because not all studies included measures of depression, fatigue, stiffness, or joint counts. A study that reported a major contribution of depression to the PGA did not include a measure of pain (8). To understand which aspects of RA influence patients’ assessments of change in their status, it is important to perform longitudinal comparisons, rather than rely on indirect between-patient comparisons of cross-sectional studies. Few longitudinal studies have investigated which RA activity measures are associated with changes in the PGA (5, 9–11). One study examined only pain and physical functioning, another only the Disease Activity Score (DAS), and the single study that examined fatigue and depression did not include joint counts. In clinical practice, informal appraisals of patients’ overall status are more common than formal measures such as the PGA. Universal questions to patients include how they feel now and if they feel better. These appraisals are retrospective judgments that, like the PGA, are intended to integrate diverse aspects of disease into a single assessment. However, because they depend on recall, changes reported retrospectively may differ from those measured prospectively on measures such as the PGA, and the validity of retrospective judgments of improvement has been questioned (12). Our first goal was to identify the RA-related measures associated with prospectively measured changes in the PGA. If changes in clinical factors other than pain were associated with changes in PGA, it would validate the PGA as a summary measure of multiple aspects of RA. We were also interested in whether depression and fatigue were independently associated with changes in the PGA. Our second goal was to identify if changes in RA activity measures were associated with patients’ retrospective judgments of improvement in overall arthritis status as a way to validate this outcome measure. Our third goal was to compare the RA activity measures that were associated with patients' retrospective judgments with those associated with the PGA. The former directly reflects the assessments provided by patients in clinical practice, and the comparison would provide insight into how patients form their appraisals of improvement.

The UEMS Otorhinolaryngology-Head and Neck Surgery section is a dedicated body formed to promote the standardisation and harmonisation of European Otorhinolaryngology (ORL). The European Examination Board of Otorhinolaryngology and Head and Neck Surgery was created to establish a supranational final exam and accreditation for ORL Surgeons. It is open to candidates both from the European Union and outside the EU. The exam is composed of a written examination to assess mainly the theoretical knowledge of Otorhinolaryngological diseases. The second part, a viva voce examination, is designed to test the clinical application of knowledge based on case scenarios and clinical conditions presented to the candidates. The inaugural examination written component took place in Mannheim/Germany in 2009 and the inaugural Viva Voce examination in Vienna/Austria in 2010. Up to and including the year 2013, 858 participants have attempted one of the two exam components. Of the 858 participants, 305 were successful in both examinations and obtained the accreditation of the European Diploma (European Board Certification). The historical origins, development of the examination, its formal arrangements and the format of the examination are presented in this article.

Background No single “gold standard” measure is available to assess patients with rheumatoid arthritis (RA) in clinical trials and routine care, as in hypertension, diabetes, and other diseases. Therefore, an index of several measures, such as a DAS28 (Disease Activity Score-28) and CDAI (Clinical Disease Activity Index), based on 7 RA core data set measures; is needed. However, the only quantitative data in many (most) patients in routine rheumatology care are laboratory test results. RAPID3 (routine assessment of patient index data), which includes only patient self-report scores, is considerably more feasible than DAS28 or CDAI for routine care, distinguishes active from control treatments in RA clinical trials similarly and is correlated significantly with these indices. A minimal clinically important improvement (MCII) to interpret changes in clinical trials and clinical care has not been established for RAPID3 Objectives To estimate MCII of RAPID3, and compare results to MCIIs of DAS28 and CDAI. Methods Post hoc analyses were performed of a reported longitudinal study of 250 patients with active RA (1). All 7 RA core data set measures were collected at baseline and after treatment escalation with prednisone 1 month later or with disease modifying medications or biologic agents 4 months later (1). Patient judgment of improvement in arthritis status was obtained as “improved”, “the same” or “worsened”, and analyzed in relation to changes in RAPID3, DAS28 and CDAI. RAPID3 is the sum of 3 0–10 measures: physical function on a HAQ recalculated from 0–3 to 0–10, pain and patient global estimate on 0–10 VAS (visual analog scales), total=0–30. DAS28-ESR (erythrocyte sedimentation rate) and CDAI were computed as described in the literature. Changes in all indices, standardized response means (SRM), MCIIs as changes that had a specificity of 0.80 for improvement based on receiver-operating characteristic curves, and MCII as a proportion of the maximum score were computed. Results Among 250 patients, 167 (66.8%) reported improvement. RA activity and SRMs improved similarly per the 3 indices (Table). ROC curve areas were ≥0.77 (Table). MCIIs with specificity for improvement of 0.80 were -3.5 for RAPID3, -1.17 for DAS28-ESR, and -12.5 for CDAI. MCIIs were in a similar range of 11.6% to 16.8% of maximum score (Table). Conclusions MCIIs for RAPID3, DAS28, and CDAI were in a similar range. Knowledge concerning MCII thresholds can improve interpretation of data from clinical trials and routine clinical care. References Ward, M et al, Ann Rheum Dis 2015, 74:1691–1696. Disclosure of Interest I. Castrejon: None declared, M. Ward: None declared, M. Bergman: None declared, L. Guthrie: None declared, M. Alba: None declared, T. Pincus Shareholder of: Health Report Services, Inc

Objective: Patient-physician discordance in health status ratings may arise because patients use temporal comparisons (comparing their current status with their previous status), while clinicians use social comparisons (comparing this patient's status to that of other patients, or to the full range of disease severity possible) to guide their assessments. We compared discordance between patients with rheumatoid arthritis (RA) and clinicians using either the conventional patient global assessment (PGA) or a rating scale with five anchors describing different health states. We hypothesized that discordance would be smaller with the rating scale because clinicians likely used similar social comparisons when making global assessments. Methods: We prospectively studied 206 patients with active RA, and assessed the PGA (0 – 100), rating scale (0 – 100), and evaluator global assessment (EGA; 0 – 100)) on each of two visits (total 401 visits). We compared the PGA/EGA discordance and the rating scale/EGA discordance at each visit. Results: The mean (± standard deviation) PGA/EGA discordance was 8.5 ± 22.4, and the mean rating scale/EGA discordance was 2.3 ± 24.0. The intraclass correlation, measuring agreement, was higher between the rating scale and EGA than between the PGA and EGA (0.39 versus 0.31). Agreement was larger at low levels of RA activity on both pairs of measures. Conclusion: Discordance between patients' global assessments and evaluators' global assessments was smaller when patients used a social standard of comparison than when they marked the PGA, suggesting that differences in standards of comparison contribute to patient-clinician discordance when the PGA is used. This article is protected by copyright. All rights reserved.

The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes. Recommendations represent systematically developed statements to help practitioners in reducing variability. However, major difficulties arise in the application of recommendations into clinical practice. In this respect, the use of quality indicators may raise the awareness among rheumatologists regarding potential deficiencies in services and improve the quality of health care. The aim of this study was to develop a set of quality indicators (QI) for SLE by translating into QIs the recently developed EULAR Recommendations for monitoring SLE patients in routine clinical practice and observational studies. Eleven QIs have been developed referring to the use of validated activity and damage indices in routine clinical practice, general evaluation of drug toxicity, evaluation of comorbidities, eye evaluation, laboratory assessment, evaluation of the presence of chronic viral infections, documentation of vaccination and of antibody testing at baseline. A disease specific set of quality assessment tools should help physicians deliver high quality of care across populations. Routine updates will be needed.

ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P < 0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P < 0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P < 0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P < 0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P < 0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

ObjectiveTo identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).MethodWe studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5 kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting pResultsExperiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10−5), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10−3). There was no observed association between radiographic severity and HLA-B*27.ConclusionsThese findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Previous studies have shown an association between duration of bisphosphonate use and atypical femur fractures. This cohort study showed an increasingly higher risk of subtrochanteric and femoral shaft fractures among those who were more adherent to oral bisphosphonates.Long-term use of oral bisphosphonates has been implicated in an increased risk of atypical femur fractures located in subtrochanteric and femoral shaft regions. Another measure of drug exposure, medication adherence, however, has not been investigated.Among all Medicare fee-for-service female beneficiaries from 2006-2010, we followed 522,287 new bisphosphonate users from their index prescription until being censored or having a primary diagnosis of closed subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures. Data about radiographs of fracture site and features were not available. Adherence was classified according to the medication possession ratio (MPR) as the following: MPR 1/3 as less compliant, MPR ≥ 1/3- 2/3 as compliant, and MPR ≥ 2/3 as highly compliant. Alternative cutoff points at 50 and 80% were also used. Survival analysis was used to determine the cumulative incidence and hazard of subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures.There was a graded increase in incidence of subtrochanteric/femoral shaft fractures as the level of adherence increased (Gray's test, P 0.001). The adjusted hazard ratio (HR) for the highly compliant vs. the less compliant was 1.23 (95% Confidence Interval [CI] 1.06-1.43) overall, became significant after 2 years of follow-up (HR = 1.51, 95% CI 1.06-2.15) and reached the highest risk in the fifth year (HR = 4.06, 95% CI 1.47-11.19). However, age-adjusted incidence rates of intertrochanteric/femoral neck fractures were significantly lower among highly compliant beneficiaries, compared to less compliant users (HR = 0.69, 95% CI 0.66-0.73). Similar results were obtained when the cutoff points for being compliant and highly compliant were set at 50 and 80 %, respectively.Subtrochanteric/femoral shaft fractures, unlike intertrochanteric/femoral neck fractures, are positively associated with higher adherence to long-term (≥3 years) oral bisphosphonates in the elderly female Medicare population.

Background:Adenoidectomy is often carried out in children for conditions such as nasal obstruction, otitis media with effusion, and obstructive sleep apnoea. Traditionally, it is performed as a blind procedure with a St Clair Thomson curette. An acceptable alternative technique is suction diathermy adenoidectomy. This study aimed to ensure that the complication rate of this latter technique was within published rates and national guidelines.Method:A retrospective case note review was conducted, and information regarding surgery, indications and complications was collected.Results:Post-operative haemorrhage was recorded for 2 of 121 patients (at days 10 and 11 post-operatively): 1 returned to the operating theatre and the other was managed conservatively. Two patients were diagnosed with infection post-operatively and managed with oral antibiotics. A further four patients re-presented with pain; in all cases, this was recorded as secondary to tonsillar fossa infection, rather than being pain related to adenoidectomy.Conclusion:Given the rare but serious potential complications, the authors support National Institute for Health and Clinical Excellence guidance, which recommends that only surgeons with specific training perform this technique. By using the standard procedures for clinical governance, it is possible to ensure safe practice of even little-used techniques.

Background Patients with ankylosing spondylitis (AS) are at higher risk for developing cardiovascular comorbidities. While aortic valve and conduction defects are most common, increased levels of LDL cholesterol are also seen. Statin usage has been reported to lower CRP and ESR though the power of these studies are limited due to small sample size and short-term follow-up (1,2). Objectives This study examines associations of statin usage with socio-demographic and clinical factors, including disease activity, functional impairment, and radiographic severity in patients with two years of follow-up or more. Methods 655 AS patients meeting modified New York criteria followed at least 2 years (and up to 12 years) were included in the analysis. Demographic and clinical parameters (disease activity and functional impairment were collected every 6 months, as well as radiographic assessments (BASRI and mSASSS) every 2 years. Univariable and multivariable mixed effect models were developed to identify independent factors associated with statin usage over time. Results Mean disease duration was 18 years (SD=13). 10% (n=66) of the cohort were using statins. Univariable longitudinal regression models are shown below: Multivariable longitudinal analyses controlling for confounders showed independent associations of age >40 years (p Conclusions Statin usage was, as expected, more likely in those of older age with greater disease duration and greater radiographic severity. Even though statins are known to reduce CRP, the association with markers of lower disease activity, both subjective (BASDAI on univariable analysis) and objective (CRP on both univariable and multivariable analyses), raises the possibility of a role in suppressing inflammation in patients with AS. References Heinemann S and Daemen M. Cardiovascular risks in spondyloarthropaties. Curt Opin Rheumatol. 2007 19:358–362. Denderen JC, Peters MJL, van Halm VP, van de Horst-Bruinsma, Dijkmans BAC, Nurmohamed MT. Statin therapy might be beneficial for patients with ankylosing spondylitis. Ann Rhem Dis. 2006; 65: 695–696. Disclosure of Interest J. Dau: None declared, M. Weisman Grant/research support from: UCB, Human Genome Sciences, Sanofi, Eli Lilly and Co, Genentech, Inc., Santarus Inc., EMD Serono, ChemoCentryx, GSK, Immunomedics Inc., Consultant for: Boehringer Ingelheim/Proskauer, Ardea Biosciences, Epirus Biopharmaceuticals, Acerta Pharma, M. Lee: None declared, M. Ward: None declared, M. Brown: None declared, L. Diekman: None declared, M. Rahbar: None declared, L. Gensler: None declared, J. Reveille: None declared

Background Radiographic damage in Ankylosing Spondylitis (AS) is largely defined by new bone formation. The beneficial effects of pharmacologic therapy on osteoproliferation have been difficult to prove. Objectives The objective of this study was to examine the relationship of NSAIDs and Tumor Necrosis Factor inhibitors (TNFi) on New bone formation in AS. Methods 511 AS patients meeting the modified New York criteria with at least 2 years of radiographic follow-up were included in this prospective longitudinal study. Progression was defined as an increase at any vertebral corner from 0/1 to 2 or 0/1 to 3 at any interval between radiographs to reflect syndesmophyte development. We grouped patients according to the interval between baseline and the last visit, and used progression as a dichotomized outcome in a mixed effect logistic regression model. Patients taking NSAIDs for more than 50% of the time between visits were considered high NSAID users for that visit. TNFi use was assessed at each visit and adjusted for baseline use and total duration. Results In our multivariable models after adjusting for significant covariates, we found that TNFi use was associated with less new bone formation in AS with the strongest association in patients who had 2.1–3.5 years of follow-up (OR=0.27; 95% CI 0.08–0.94; p=0.04) [Table 1]. Though not statistically significant, in patients who were followed up for 3.6 years or longer, the odds of progression for the TNFi user group was 41% (3.6–5.9 year group) and 14% (6+ year group) lower than in non-users (OR=0.59, OR=0.86). We found a significant interaction (p=0.01) between NSAID use and TNFi in relation to radiographic progression. Those patients exposed to both TNFi and with high NSAID use had an OR for progression of 0.31, 95% CI 0.13–0.75, compared to those not on high dose NSAIDs (OR=1.23, 95% CI 0.41–3.66). Conclusions TNFi are associated with less new bone formation in AS, and this appears to be modified by the use of NSAIDs. Disclosure of Interest L. Gensler Consultant for: AbbVie, Amgen, Janssen, Novartis, UCB, J. Reveille: None declared, M. Ward: None declared, M. Brown Grant/research support from: Janssen, Abbvie, UCB, Leo Pharma, Complete Genomics, Consultant for: Abbvie, UCB, Janssen, Pfizer, Speakers bureau: Abbvie, UCB, Pfizer, UCB, M. Rahbar: None declared, M. Lee: None declared, M. Weisman Grant/research support from: UCB, Human Genome Sciences, Sanofi, Eli Lilly and Co, Genentech, Inc., Santarus Inc., EMD Serono, ChemoCentryx, GSK, Immunomedics Inc., Consultant for: Boehringer Ingelheim/Proskauer, Ardea Biosciences, Epirus Biopharmaceuticals, Acerta Pharma

Background Pharmacologic therapies in Ankylosing Spondylitis (AS) have informed debatable effects on radiographic progression. Two-year studies using Tumor Necrosis Factor inhibitors (TNFi) showed no benefit, yet longer-term studies reported less radiographic progression. Similarly, NSAID effects have been controversial. Objectives To determine the relationship between pharmacologic therapies and radiographic progression in AS. Methods This is a prospective cohort of 505 AS patients meeting the modified New York criteria with at least 2 years of radiographic follow up. Using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), progressors were defined with at least one mSASSS unit increase per year of follow up or patients who rapidly progressed at any time point (2 new syndesmophytes in 2 years). Patients with an mSASSS=72 at baseline (n=17) were excluded. TNFi use was defined at each 6-month study visit and adjusted for baseline use and total duration of use. High NSAID use was defined if the patient was taking NSAIDs at least 50% of the study period. We grouped patients according to their follow-up period (interval between baseline and last visit) and used progressor status (progressor vs. non-progressor) as a dichotomized outcome in univariable and multivariable mixed effects logistic regression models. Results The progressors made up 35.45% of the cohort (n=179). We found that TNFi use was related to a lower likelihood of radiographic progression and this association appeared to be strongest for patients with 2.1–3.5 years of follow-up (OR=0.25, 95% CI 0.07,0.92; p=0.0376). Although not statistically significant, in patients who were followed up for 3.6 years or longer, the odds of progression for the TNFi user group was 46% lower in the 3.6–5.9 year group (OR=0.54) and 23% lower in the 6+ year group (OR=0.77) than in TNFi non-users. Patients exposed to NSAIDs (≥50% exposure) also had a lower likelihood of radiographic progression (OR=0.47, 95% CI 0.22,0.99); p=0.046) [Table 1]. The probability of progression by years of follow up per TNFi user group is shown in Figure 1. Conclusions TNFi use is associated with a lower likelihood of radiographic progression in AS with the most significant effect after longer than 2 years of follow up. Use of NSAIDs was also associated with less radiographic progression. Disclosure of Interest L. Gensler Consultant for: AbbVie, Amgen, Janssen, Novartis, UCB, J. Reveille: None declared, M. Ward: None declared, M. Brown Grant/research support from: Janssen, Abbvie, UCB, Leo Pharma, Complete Genomics, Consultant for: Abbvie, UCB, Janssen, Pfizer, Speakers bureau: Abbvie, UCB, Pfizer, UCB, M. Rahbar: None declared, M. Lee: None declared, M. Weisman Grant/research support from: UCB, Human Genome Sciences, Sanofi, Eli Lilly and Co, Genentech, Inc., Santarus Inc., EMD Serono, ChemoCentryx, GSK, Immunomedics Inc., Consultant for: Boehringer Ingelheim/Proskauer, Ardea Biosciences, Epirus Biopharmaceuticals, Acerta Pharma

Objectives: To develop recommendations for monitoring patients with systemic lupus erythematosus (SLE) in clinical practice and observational studies and to develop a standardised core set of variables to monitor SLE. Methods: We followed the European League Against Rheumatism (EULAR) standardised procedures for guideline development. The following techniques were applied: nominal groups, Delphi surveys for prioritisation, small group discussion, systematic literature review and two Delphi rounds to obtain agreement. The panel included rheumatologists, internists, dermatologists, a nephrologist and an expert related to national research agencies. The level of evidence and grading of recommendations were determined according to the Levels of Evidence and Grades of Recommendations of the Oxford Centre for Evidence-Based Medicine. Results: A total of 10 recommendations have been developed, covering the following aspects: patient assessment, cardiovascular risk factors, other risk factors (osteoporosis, cancer), infection risk (screening, vaccination, monitoring), frequency of assessments, laboratory tests, mucocutaneous involvement, kidney monitoring, neuropsychological manifestations and ophthalmology assessment. A ‘core set’ of minimal variables for the assessment and monitoring of patients with SLE in clinical practice was developed that included some of the recommendations. In addition to the recommendations, indications for specifi c organ assessments that were viewed as part of good clinical practice were discussed and included in the fl ow chart. Conclusions: A set of recommendations for monitoring patients with SLE in routine clinical practice has been developed. The use of a standardised core set to monitor patients with SLE should facilitate clinical practice, as well as the quality control of care for patients with SLE, and the collection and comparison of data in observational studies.

Experiments were performed to test the ability of mouse antiidiotopic mAb, specific for an antilipid A mAb, to act as a vaccine against gram-negative bacterial infections. Lipid A is a conserved region of bacterial LPS. Immunization with the antiidiotopic antibodies, coupled to an immunogenic carrier protein (hemocyanin), specifically induced anti-LPS antibody responses in animals from different species. In a mouse model, this immunization resulted in protection against both lethal gram-negative bacteremia and endotoxemia. The antiidiotopic antibodies, however, did not stimulate endotoxin-associated bioactivities, such as induction of TNF and IL-1. These results support the hypothesis that an idiotope vaccine can stimulate beneficial protective immunity against gram-negative infections without the toxicity inherent in LPS.

Objective To analyze the minimum clinically important improvement (MCII) of disease activity measures in rheumatoid arthritis (RA) using patient-derived anchors, and to assess whether criteria for improvement differ with baseline disease activity. Methods We used data from a Norwegian observational database comprising 1,050 patients (73% women, 65% rheumatoid factor-positive, mean duration of RA 7.7 years). At 3 months after initiation of therapy, patients indicated whether their condition had improved, had considerably improved, was unchanged, had worsened, or had considerably worsened. We used receiver operating characteristic curve analysis to determine the MCII for the Disease Activity Score based on the assessment of 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), and analyzed the effects of different levels of baseline disease activity on the MCII. Results On average, patients started with high disease activity and improved significantly during treatment (American College of Rheumatology 20%, 50%, and 70% improvement criteria responses were 37%, 17%, and 5%, respectively). The overall mean (95% confidence interval [95% CI]) thresholds for MCII after 3 months for the DAS28, SDAI, and CDAI were 1.20 (95% CI 1.18–1.22), 10.95 (95% CI 10.69–11.20), and 10.76 (95% CI 10.49–11.04), respectively, and the mean (95% CI) thresholds for major responses were 1.82 (95% CI 1.80–1.83), 15.82 (95% CI 15.65–16.00), and 15.00 (95% CI 14.82–15.18), respectively. With increasing disease activity, much higher changes in disease activity were needed to achieve MCII according to patient judgment. Conclusion The perception of improvement of disease activity of patients with RA is considerably different depending on the disease activity level at which they start.

Experiments were performed to test the hypothesis that Ly-1 B cells respond to antigenic challenge with LPS from gram-negative bacteria. To perform these experiments, the splenic fragment culture system for the study of B cell precursors was used. We found that a significant number of anti-O/core, but not anti-lipid A, precursors expressed the lambda L chain. A restriction of the anti-LPS response to Ly-1 B cells was tested using a Ly-1 depletion protocol. We found that the anti-O/core antibody response was restricted to the Ly-1 B cell lineage. In contrast, conventional B cells, not Ly-1 B cells, respond to an antigenic challenge with lipid A. Our results further support the idea that the Ly-1 B cell lineage serves a direct role in protecting against certain bacterial infections.

To determine the treatments used by patients with ankylosing spondylitis (AS), and to compare these treatments with those recommended by rheumatologists, we surveyed 226 patients with AS, and also surveyed 123 American rheumatologists about their judgments of the effectiveness of different treatments for AS. One hundred eighty-eight patients (83.2%) used nonsteroidal anti-inflammatory drugs (NSAIDs), 62 patients (27.4%) used analgesics, 38 patients (16.8%) used second-line medications, and 22 patients (9.7%) used no medications. Fifty-seven patients (25.2%) were using indomethacin, 8 (3.5%) were using phenylbutazone, 26 (11.5%) were using sulfasalazine, 12 (5.3%) were using methotrexate, and 28 (12.4%) were receiving physical therapy. Results were similar in the subgroup of patients (N = 112) who rated their AS moderately or very active. In contrast, 81% of rheumatologists rated indomethacin either extremely effective or very effective in treating active AS, as did 90% for phenylbutazone. Eighty-two percent of rheumatologists recommended indomethacin for most patients with active AS; 64% recommended sulfasalazine, and 20% recommended methotrexate for most patients who had inadequate responses to NSAIDs. Many patients who report active AS, including many of those treated by rheumatologists, are not using treatments, including drugs and physical therapy, commonly recommended by rheumatologists for patients with active AS. Understanding the reasons for this discordance may suggest ways to improve the health of these patients. Clinicians should review and discuss the treatments received by their patients with AS to ensure that appropriate treatment is being provided.

Contains fulltext : 71181.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Contains fulltext : 69269.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.

LPS is the major surface glycolipid on gram-negative bacteria. In this work, we have idiotypically characterized the antibody response against LPS in different species. To do this, we have produced mAb against LPS. Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule. One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models. We generated anti-idiotypic antibodies against IC9. The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A. We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species. The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed.

Background: Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). Methods: Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as “biologics”, or “traditional” disease modifying antirheumatic drugs (DMARDs), and “placebo”. We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. Results: We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. Conclusion: Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.

Heart valve replacement surgeries account for 20% of all cardiac procedures. In-hospital mortality rates are approximately 6% for aortic valve replacements and 10% for mitral valve replacements. The objectives of the study are to provide nationally representative estimates of complications following aortic and mitral valve replacements and to quantify the impact of different types of complications on in-hospital outcomes.The Nationwide Inpatient Sample was analyzed for years 2000-2003. The effect of complications on in-hospital mortality, length of stay (LOS), and hospital charges were examined using bivariate and multivariable logistic and linear regression analyses. The confounding effects of age, sex, primary diagnosis, type of valve replacement, type of admission, comorbid conditions, and hospital characteristics were adjusted.A total of 43,909 patients underwent aortic valve replacement as the primary procedure during the study period and 16,516 patients underwent mitral valve replacement. Complications occurred in 35.2% of those undergoing aortic valve replacements and in 36.4% of those undergoing mitral valve replacements. Almost half of these are cardiac complications and a quarter involve hemorrhage/hematoma/seroma. Complications were significantly associated with in-hospital mortality, LOS, and hospital charges even after adjusting for patient and hospital characteristics.Complications are prevalent and exert a considerable influence on outcomes following aortic and mitral valve replacements. Quality initiatives should focus on minimizing complications and improving processes of care that would enable complications to be better resolved if they occur.

Background Treat-to-target recommendations identified “remission” as a target in SLE but recognize that there is no generally accepted definition for remission in this disease. Objectives To achieve consensus, in a large multi-party international panel, on potential definitions for remission in SLE. Methods An international expert panel of sixty rheumatologists, nephrologists, dermatologists, clinical immunologists, and patient representatives participated in preparatory exercises, a full-day face-to-face meeting, and follow-up exercises and electronic voting rounds. Results Eight key statements regarding remission in SLE achieved >90% agreement (table). There were different viewpoints on the required duration of remission. In addition, the panel expressed strong support (>90%) for the following principles which will guide the further development of remission definitions: I. A definition of remission in SLE will be worded as follows: Remission in SLE is a durable state characterized by [a definition of: absence of symptoms, signs, abnormal labs, (serology)] Ia. Remission-off-therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials. Ib. Remission-on-therapy allows patients to be treated with maintenance antimalarials, stable, low-dose steroids (prednisone ≤5 mg/d), maintenance immunosuppressives and/or stable (maintenance) biologics. II. Assessment of clinical symptoms and signs should be based on a validated index, e.g., clinical-SLEDAI =0, BILAG D/E only, clinical ECLAM =0; supplemented with PhysGA III. For testing the construct validity of each potential remission definition the most appropriate outcomes (dependent variables) are: Death, Damage, Flares, and HR-QOL measures. Conclusions The work of this international consensus panel provides a framework for testing individual definitions of remission against longer-term outcomes. Disclosure of Interest R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, C. Aranow: None declared, G. Bertsias: None declared, E. Bonfa: None declared, R. Cervera: None declared, N. Costedoat-Chalumeau: None declared, T. Dorner: None declared, F. Houssiau: None declared, K. Lerstrom: None declared, E. Morand: None declared, M. Mosca: None declared, S. Navarra: None declared, M. Petri: None declared, M. Urowitz: None declared, A. Voskuijl: None declared, A. Voss: None declared, M. Ward: None declared, V. Werth: None declared, M. Schneider: None declared

There are four major challenges in the assessment of outcomes in patients with ankylosing spondylitis (AS) that are particularly relevant to the evaluation of new therapies. Firstly, measures of symptoms and impairment in AS are not specific for inflammatory processes, they also capture mechanical symptoms and fixed limitations. The non-specific nature of these measures may cause them to be less responsive and therefore less useful in determining treatment efficacy. Secondly, acute phase reactants have limited value as measures of AS activity and other surrogate markers have not yet been established. Thirdly, the assessment of the disease modifying potential of new therapies is hampered by the slow rate of spinal fusion. Fourthly, work disability has not be studied as an endpoint in clinical trials in AS, despite the fact that work disability is an important outcome in patients with AS. Research into ways to overcome these challenges in outcome measurement will help identify useful therapies and define the range of outcomes that they influence.

The Finnish type of familial amyloid polyneuropathy due to variant gelsolin is a rare form of familial amyloidosis. The subtype was first described in 1969 and is characterized by progressive cranial neuropathies, corneal lattice dystrophy and distal sensorimotor dysfunction. It is extremely uncommon, with only two families known to be affected in the UK. We discuss the case of a 70-year-old woman who presented with bilateral facial nerve palsies, bilateral sensorineural hearing loss and Finnish type familial hereditary amyloidosis. A literature search of the Medline database (1966–2005) was performed, using the keywords ‘amyloid’, ‘hearing loss’ and ‘facial palsy’; however, this association appears to be a novel finding. We review the current literature and discuss otorhinolaryngological presentations of amyloidosis.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

Patients whose perspectiveis oriented to the future more than to the present may have better long-term health outcomes. We examined if time perspective predicted future organ damage in patients with systemic lupus erythematosus(SLE). We assessed the time perspectivesof 87 patients with SLE using a questionnaire at a baseline visit. Permanent organ damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index during the same visit, and reassessed after a median of 4.6 years. Patients who were oriented more to the futurewere less likely to have an increasein the Damage Index than those oriented more to the present. In a multivariate analysis, each 1-point increase in the degree of orientation to the future (on a scale of 1-6) was associatedwith a 22% decreasein the likelihood that the Damage Index would increase over time (odds ratio 0.78; 95% confidence interval 0.64-0.94; P 0.009). Other measures that predicted an increase in the Damage Index were lower education levels, greater health locus of control attributed to chance and greater health locus of control attributed to powerful others. In conclusion, time perspective is a significant predictor of future organ damage in SLE. Patients who have a greater orientation to the future are less likely to develop permanent organ damage.

Objective To determine if changes in depressive symptoms or anxiety lead to changes in the activity of systemic lupus erythematosus (SLE). Methods Twenty-three patients with SLE were examined prospectively every 2 weeks for up to 40 weeks. At each assessment, patients completed the Centers for Epidemiologic Studies--Depression scale (CES-D), the State subscale of the State-Trait Anxiety Inventory and a global assessment of the activity of their SLE by visual analogue scale. SLE activity was also assessed at each visit by physician global assessment, the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure (ECLAM). Results Changes in depression and anxiety were positively correlated with simultaneous changes in the patient global assessment of SLE activity and in the SLAM, but not with changes in the physician global assessment, SLEDAI or ECLAM. Depression and anxiety scores were also correlated with patient global assessments and SLAM scores 2 weeks later, but lagged scores were not significantly associated with the patient global assessment or SLAM after controlling for current depression and anxiety scores. The associations between depression and anxiety scores and the SLAM were not present when SLAM scores were modified to exclude ratings of depression and fatigue. No measure of SLE activity increased in the 2 weeks immediately after a large increase in CES-D or State Anxiety scores. Conclusions Depression and anxiety scores parallel changes in patients' assessments of the activity of their SLE. We found no evidence to support the hypothesis that psychological distress causes increased SLE activity.

We present the first documented case of Kearns-Sayre syndrome presenting with a vocal fold palsy.

This paper describes a clinical situation where it was impossible to obtain a biopsy of a lesion at the anterior commissure in a patient with progressive hoarseness of voice using standard microlaryngoscopy techniques. Due to anatomical difficulties and a histological suggestion of laryngeal papillomatosis the incisor teeth were deliberately removed to allow an adequate view of the larynx and to facilitate further access.

To identify risk factors for work disability in patients with ankylosing spondylitis (AS).Risk factors for permanent work disability and for receipt of disability payments were assessed using Cox regression models in a retrospective cohort study of 234 patients with AS. Candidate risk factors included age at onset of AS, sex, race, education level, marital status, the presence of comorbid conditions, smoking and drinking history, recreational activity, occupation, and physical activity at work. Risk factors for changes in the type of work performed, decrease in number of hours worked, long sick leave, and the need for help at work were assessed using logistic regression models in a prospective study of the subset of 144 patients who reported working for pay during the study. Candidate risk factors for these aspects of work disability were age, sex, race, education level, levels of functional disability, pain and stiffness, changes in functional disability, pain or stiffness over the preceding 6 months, minutes/week of recreational exercise, back exercises, freedom of movement at work, control over the pace of work, and physical activity at work.In a cohort of 234 patients with a median duration of AS of 21.4 years, 31 patients (13.2%) developed permanent work disability and 57 patients (24.3%) had received disability payments. Older age at onset of AS, less formal education, and having had jobs that were more physically active were significant risk factors for permanent work disability. These factors, along with the presence of a comorbid condition and being female, were also significantly associated with the receipt of disability payments. In a prospective study of 144 patients followed for a median of 4 years, higher levels of functional disability and pain were associated with increased risks of decreased work hours, long sick leaves, and needing help at work, while higher levels of pain were also associated with an increased risk of changing the type of work performed. Women were significantly more likely than men to change their type of work or decrease their work hours. Patients whose jobs were more physically demanding were more likely to change their type of work or need help at work.Patients with AS who have physically demanding jobs are more likely to experience permanent or temporary work disability, or need to change the type of work done or receive help at work, than those with jobs that are less physically demanding.

Preference measures may be useful tools to assess patients' overall health-related quality of life. We studied the validity and sensitivity to change of the rating scale preference measure in patients with systemic lupus erythematosus (SLE), and compared its properties with those of the patient global assessment of SLE activity, in a prospective longitudinal observational study of changes in the symptoms and clinical disease activity of 23 patients. Patients were assessed every two weeks for up to 40 weeks. Construct validity was assessed by the strength of correlations between changes over time in the rating scale preference measure and patient global assessment and changes in the physician global assessment, Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measure (ECLAM), the British Isles Lupus Assessment Group index (BILAG), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Changes in the rating scale were more highly correlated with changes in each of these standards than were changes in the patient global assessment, demonstrating the construct validity of this measure. Sensitivity to change was measured using the two-week interval of greatest change in either the physician global assessment or the SLE activity measures as standards. The rating scale preference measure was less sensitive to change than the patient global assessment when tested against four different standards. The sensitivity to change of the rating scale was less than one-half that of the patient global assessment when either the SLAM or ECLAM was used as the standard. Although these results support the validity of the rating scale as a measure of health-related quality of life in patients with SLE, its limited sensitivity to change may make it less attractive as an endpoint measure in clinical trials.

To determine whether a hospital's experience in treating patients with systemic lupus erythematosus (SLE) is associated with the risk of in-hospital mortality among these patients.The California Hospital Discharge Database, which contains information on all discharges from acute care hospitals in California, was used to identify patients with SLE hospitalized on an emergent or urgent basis from 1991 to 1994 (n = 9,989). For each of the 413 hospitals at which these patients were hospitalized, expected mortality risks were computed based on a model that included patient demographic and clinical characteristics, and differences between the observed and expected numbers of deaths were calculated. This difference was then associated with the average annual number of patients with SLE admitted to each hospital on an emergent or urgent basis. Similar analyses were performed for the subset of 2,372 patients hospitalized on an emergent basis (at 293 hospitals), and the subset of 405 patients hospitalized on an emergent basis due to SLE (at 122 hospitals).In all 3 patient subsets, there was an inverse association between the average annual number of patients with SLE hospitalized on an urgent or emergent basis at a hospital and the difference between the observed and expected number of deaths at that hospital. Highly experienced hospitals had fewer than expected deaths, while there was little association between the difference between the observed and expected number of deaths among less experienced hospitals.Hospitals that treat larger numbers of patients with SLE have fewer than the expected number of deaths among such patients.

Valid comparison of patient outcomes among hospitals requires adjustment for differences in the severity of patients' illness. Disease-specific indexes of severity of illness may permit more accurate risk adjustment than generic indexes. The objective of this study was to develop a systemic lupus-specific risk adjustment index for in-hospital mortality, and to compare its performance to that of the generic Charlson index.A systemic lupus-specific risk adjustment index was developed using discharge abstract data from a 50% random sample (n = 4994) of patients with systemic lupus erythematosus (SLE) hospitalized on an emergent or urgent basis in California from 1991 to 1994 (n = 9989). The index was tested on the remaining members of the sample. Candidate variables for the index were the diagnoses included in the original Charlson index, and nephritis, chronic renal failure, pericarditis, pleuritis, psychosis, seizures, hemolytic anemia, and thrombocytopenia. Multivariate logistic regression analysis was used to identify the set of variables that best differentiated those patients who died in the hospital from those who survived, and to provide the weights for construction of the index.In the derivation set of patients, the SLE-specific index accurately predicted in-hospital mortality (area under the receiver operating characteristic curve c = 0.79). In the test set, the SLE-specific index (c = 0.72) was similar to the original Charlson index (c = 0.74) in its ability to predict in-hospital mortality (p = 0.32). However, the SLE-specific index accounted for substantially more variation in the risk of mortality among patients (R2 = 0.069) than did the Charlson index (R2 = 0.036). Use of the SLE-specific index rather than the Charlson index for risk adjustment did not alter the association between hospital experience and the probability of in-hospital mortality. Results were similar in the subgroups of patients with emergent hospitalizations and those with emergent hospitalizations due to SLE.The SLE-specific risk adjustment index developed from diagnoses recorded in administrative discharge abstracts performed similarly to the generic Charlson index in correctly classifying mortality outcomes, but the SLE-specific index stratified patients by their level of risk of mortality better than the Charlson index. Adjustment for SLE-specific risks of mortality did not alter the association between hospital experience and the risk of in-hospital mortality.

To compare the construct validity and sensitivity to change of the Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Lupus Activity Index (LAI), British Isles Lupus Assessment Group index (BILAG), and the European Consensus Lupus Activity Measure (ECLAM).Twenty-three patients with systemic lupus erythematosus (SLE) were examined prospectively every 2 weeks for up to 40 weeks. Nineteen patients completed all 20 assessments. At each assessment, each of the 5 activity indices was scored, along with physicians' and patients' global assessments of SLE activity. Construct validity was determined by the strength of correlations between changes over time in each activity index and changes in physician and patient global assessments. Sensitivity to change was determined by the magnitude of change in each index over the 2 week interval of greatest change in the physician or patient global assessments, and calculated as standardized response means (SRM; mean change/standard deviation of change). Thirteen patients were also examined monthly by a second physician who was blinded to previous scores on the activity indices and to the patient global assessments.Patients had substantial changes in SLE activity during the study. Changes in each activity index were correlated with changes in the physician global assessment (SLAM r = 0.54; SLEDAI r = 0.52; LAI r = 0.75; BILAG r = 0.61; ECLAM r = 0.65; all p0.0001). Correlations were somewhat lower with the blinded physician assessment (SLAM r = 0.42; SLEDAI r = 0.12; LAI r = 0.30; BILAG r = 0.28; ECLAM r = 0.32). The SLAM was the only index that was positively correlated with changes in the patient global assessment (r = 0.22; p0.0001). Sensitivity to change was greatest for the LAI (SRM = 0.74) and the ECLAM (SRM = 0.75) and smallest for the SLEDAI (SRM = 0.48) when the physician global assessment was used as the standard. Sensitivity to change was greatest for the SLAM (SRM = 0.61) and the BILAG (SRM = 0.57) and smallest for the SLEDAI (SRM = -0.01) when the patient global assessment was used as the standard.Each index is a valid measure of SLE activity. The SLAM captures patients' assessments better than the other indices, perhaps because it assesses the patients' subjective complaints to a greater extent. Estimates of sensitivity to change varied with the standard used, but the SLEDAI was least sensitive to change. Larger studies are indicated to further compare the sensitivity to change of these indices.

To identify aspects of health-related quality of life that are most commonly affected in patients with ankylosing spondylitis (AS).One hundred seventy-five participants in a longitudinal study of health status in AS completed a cross-sectional survey that asked them to rate the presence and importance of problems in 23 aspects of quality of life, including symptoms, disability, mood, relations with others, and concerns about treatments and the future. Participants also completed the Medical Outcomes Study Short Form 36 Health Survey (SF-36).The mean age of the participants was 51.1 years, and the mean duration of AS was 23.7 years; 119 (68%) were men. The most prevalent quality of life concerns included stiffness (90.2%), pain (83.1%), fatigue (62.4%), poor sleep (54.1%), concerns about appearance (50.6%), worry about the future (50.3%), and medication side effects (41%). Compared with those who had some college education, participants with 12 years of education or less were 2 to 4 times more likely to have problems or concerns with medication side effects, mobility, housework and self-care tasks, coping with illness, anxiety, payment for treatment, and relationships with spouses, family, and friends. Mean scores on the 8 domains of the SF-36 (range 0-100; higher scores indicate better function) ranged from 49 (energy/fatigue) to 77 (role limitations due to emotional problems). Patients with 12 years of education or less had significantly lower scores than those with some college on all domains except general health.In addition to pain and stiffness, fatigue and sleep problems are important concerns in patients with AS, while few reported problems with mood or social relationships. Less educated patients had lower quality of life in many different aspects.