Search

Long-term glucocorticoid (GC) therapy is frequently indicated to treat autoimmune and chronic inflammatory diseases in daily clinical practice. Two of the most devastating untoward effects are bone loss and fractures. Doses as low as 2.5 mg of prednisone for more than 3 months can impair bone integrity. Population at risk is defined based on the dose and duration of GC therapy and should be stratified according to FRAX (Fracture Risk Assessment Tool), major osteoporotic fracture, prior fractures, and bone mineral density values (BMD). General measures include to prescribe the lowest dose of GC to control the underlying disease for the shortest possible time, maintain adequate vitamin D levels and calcium intake, maintain mobility, and prescribe a bone acting agent in patients at high risk of fracture. These agents include oral and intravenous bisphosphonates, denosumab, and teriparatide.

Objectives To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. Methods This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Results The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p Conclusions FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

Since first recognized in July 2019, numerous cases of a lung illness associated with electronic-cigarette use or vaping particularly tetrahydrocannabinol in adolescents and adults have been reported. As of January 2020, the Center for Disease Control has reported over 2500 cases of electronic-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths. Affected patients most commonly present with respiratory or gastrointestinal complaints although neurological symptoms including headache, confusion and lethargy have been reported. We present a new as yet unpublished finding in the brain of a previously healthy teenage boy with EVALI. Brain imaging may be warranted in this patient population.

Background The Center for Disease Control (CDC) has identified a national outbreak in the United States of over 2600 cases of e-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths as of January 2020. We describe our experience in six adolescents. Material and methods We identified all pediatric patients diagnosed with EVALI by CDC guidelines over a 6-month period at our health system. Clinical presentation, hospital course, and imaging were reviewed. Results Six patients were identified (three males, three females; median age 18.5 years). Presenting symptoms varied, including constitutional, gastrointestinal, neurologic, and respiratory complaints with pulmonary symptomatology becoming the dominant feature of the illness. Three patients required intensive care unit-level care, one of whom expired 36 days after presentation. Three had bronchoalveolar lavage, two with evidence of lipid-laden macrophages. Four had pulmonary function testing with various results. Admission chest radiographs in all revealed bibasilar interstitial infiltrate which rapidly progressed. Five patients had computed tomography chest imaging demonstrating: confluent pulmonary infiltrates with subpleural sparing (n = 2), generalized ground-glass opacities (n = 1), patchy ground-glass opacities (n = 1) and a reticulonodular pattern (n = 1). Brain magnetic resonance imaging (MRI) obtained in two patients was normal in one and showed a focal signal abnormality in the corpus callosum in one. Conclusion We describe the clinical course and radiologic findings of EVALI in our adolescent patients and present a new finding in the brain not yet described in the literature. Given the diversity of presenting symptoms, a high level of suspicion for EVALI is necessary for patients reporting vaping product use regardless of the presence of pulmonary complaints. Brain MRI should be strongly considered in patients with neurologic symptoms.

Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.

RESUMEN Introducción: La herramienta FRAX ha sido validada y adaptada a diferentes países, cubriendo a casi el 80% de la población mundial, incluido Ecuador, donde fue adaptada en 2009. El objetivo de este estudio fue elaborar curvas de evaluación e intervención basadas en FRAX Ecuador. Métodos: Utilizando el modelo FRAX Ecuador, calculamos la probabilidad de fractura osteoporótica mayor y fractura de cadera femenina sin ningún factor de riesgo y sin la inclusión de DMO. Las probabilidades se calcularon en intervalos de 5 años de 40 a 90 años. Las probabilidades de fractura mayor y de cadera se calcularon en 3 escenarios diferentes: 1. Historia de fractura previa sin la inclusión de DMO, 2. T-Score de -2,5 SD sin otros factores de riesgo clínico, 3. T-Score -1,5 SD sin otros factores de riesgo clínico. Resultados: En mujeres sin factores de riesgo, la probabilidad de fractura osteoporótica mayor aumentó con la edad del 0,4% a los 40 años al 7,3% a los 90 años. La probabilidad de fractura de cadera aumentó con la edad de 0% a los 40 años a 3,6% a los 90 anos. La probabilidad de fractura osteoporótica mayor aumentó en mujeres con un puntaje T de -2,5 SD de 0,9% a los 40 años a 5,5% a los 90 años; con puntaje T de -1,5 DE, de 0,6% a los 40 años a 3,9% a los 90 anos. Conclusión: Los datos muestran la importancia de aplicar herramientas como FRAX, específicas para cada país y también la creación de curvas de evaluación e intervención que permitan discernir según cada paciente la necesidad de utilizar recursos como DXA y tratamientos específicos. ABSTRACT Introduction: FRAX has been validated and adapted to different countries, covering almost 80% of the world's population, including Ecuador where it was adapted in 2009. The purpose of this study is to elaborate evaluation and intervention curves based on FRAX Ecuador. Methods: Using the FRAX Ecuador model, we calculated the probability of a major osteoporotic fracture and a female hip fracture without any risk factor and without the inclusion of BMD. The probabilities were calculated in 5-year intervals from 40 to 90 years. The probabilities of major fractures and hip fractures were calculated in 3 different scenarios: 1. History of previous fracture without the inclusion of BMD, 2. T score -2.5 SD without other clinical risk factors, 3. T score -1.5 SD without other clinical risk factors. Results: In women without risk factors, the probability of a major osteoporotic fracture increased with age from 0.4% at 40 years to 7.3% at 90 years. The probability of hip fracture increased with age from 0% at 40 years to 3.6% at 90 years. The probability of a major osteoporotic fracture increased in women with a T score of -2.5 SD from 0.9% at 40 years to 5.5% at 90 years; with a T-score of -1.5 SD, from 0.6% at 40 years to 3.9% at 90 years. Conclusion: Data shows the importance of applying tools such as FRAX, specific for each country and also the creation of evaluation and intervention curves that allow discerning according to each patient the need for the use of resources such as DXA and specific treatments.

Purpose To analyze the change in utilization of healthcare resources through a review of ultrasound examinations performed in the emergency department of an urban healthcare system in NYC during the time of peak COVID-19 outbreak. Methods This is a retrospective review analyzing ED ultrasound exams performed by the radiology department of an urban healthcare system during the 8-week time period of the peak COVID-19 outbreak in NYC, compared to a time-matched period one year prior. Data regarding the examination type and indication were obtained in addition to patient demographics and indicators of outcomes including admission, length of stay, and mortality. Results There was a 58% decrease in ED ultrasounds performed by the radiology department during the COVID-19 time period. Exams performed during the pandemic compared to the pre-pandemic period were more likely to be performed on men (28.3 vs 18.0%, p

ObjectiveThis analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).MethodsThis was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population.ResultsOf 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP) ConclusionFIL200 + MTX efficacy and safety in patients with multiple PPFs were similar to the overall population.

Objective: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for

Context The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. Objective This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. Participants and Methods Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than –2.5 to greater than –4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. Results Most participants (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. Conclusion The safety and efficacy of denosumab did not differ among participants with mild to moderate CKD.

Background Filgotinib (FIL), an orally administered, potent, selective inhibitor of janus kinase 1 (JAK1), has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA). The objectives of this study were to compare efficacy and safety of FIL with and without methotrexate (MTX) in patients with RA who were naïve to MTX therapy. Methods This Phase 3, double-blind, active-controlled study randomised patients with moderately to severely active RA (2:1:1:2) to FIL 200mg daily+MTX, FIL 100mg+MTX, FIL 200mg (+placebo [PBO]), or MTX (+PBO) up to 52 weeks; results are through week 24. Primary endpoint was proportion achieving ACR20 response at week 24. Safety endpoints included adverse events types and rates. Results Of 1,252 randomised patients, 1,249 received study drug (416 FIL 200mg+MTX; 207 FIL 100mg+MTX; 210 FIL 200mg monotherapy; 416 MTX monotherapy) and were analysed; 1,130 completed week 24. Most (76.9%) were female; mean time since RA diagnosis was 2.2 years (median 0.4 years); mean (standard deviation [SD]) DAS28-CRP was 5.7 (1.0); and 35.9% were using oral steroids at baseline. At week 24, significantly more patients in the FIL 200mg+MTX (81.0%; P Conclusion The JAK1 inhibitor FIL in combination with MTX led to significant improvements in RA signs and symptoms, physical function, and patient-reported outcomes compared to MTX alone and was well tolerated in patients with early active RA naïve to MTX. Clinically meaningful response to FIL occurred as early as 2 weeks after treatment initiation. Disclosures N. McKay: None. D. van der Heijde: Corporate appointments; Director of Imaging Rheumatology bv. Consultancies; Consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda Pharmaceutical Company Ltd., UCB. R. Westhovens: Corporate appointments; Advisor for Celltrion and Galapagos/Gilead. Other; Advisor for Celltrion and Galapagos/Gilead. W.F.C. Rigby: Consultancies; Consultant for Gilead. D.W.T. Ching: Corporate appointments; Speaker for AbbVie. Member of speakers’ bureau; Speaker for AbbVie. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Z. Yin: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. N. Mozaffarian: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. O.D. Messina: Honoraria; Received Honoraria from Pfizer, Amgen, and Americas Health Foundation (AHF). R.B.M. Landewé: Consultancies; Consultant for AbbVie, AstraZeneca, BMS, Galapagos, Pfizer, Eli Lilly, Novartis, and UCB. T. Atsumi: None. G.R. Burmester: Honoraria; Received Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.

Summary Economic evaluations are increasingly used to assess the value of health interventions, but variable quality and heterogeneity limit the use of these evaluations by decision-makers. These recommendations provide guidance for the design, conduct, and reporting of economic evaluations in osteoporosis to improve their transparency, comparability, and methodologic standards. Introduction This paper aims to provide recommendations for the conduct of economic evaluations in osteoporosis in order to improve their transparency, comparability, and methodologic standards. Methods A working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis to make recommendations for the design, conduct, and reporting of economic evaluations in osteoporosis, to define an osteoporosis-specific reference case to serve a minimum standard for all economic analyses in osteoporosis, to discuss methodologic challenges and initiate a call for research. A literature review, a face-to-face meeting in New York City (including 11 experts), and a review/approval by a larger group of experts worldwide (including 23 experts in total) were conducted. Results Recommendations on the type of economic evaluation, methods for economic evaluation, modeling aspects, base-case analysis and population, excess mortality, fracture costs and disutility, treatment characteristics, and model validation were provided. Recommendations for reporting economic evaluations in osteoporosis were also made and an osteoporosis-specific checklist was designed that includes items to report when performing an economic evaluation in osteoporosis. Further, 12 minimum criteria for economic evaluations in osteoporosis were identified and 12 methodologic challenges and need for further research were discussed. Conclusion While the working group acknowledges challenges and the need for further research, these recommendations are intended to supplement general and national guidelines for economic evaluations, improve transparency, quality, and comparability of economic evaluations in osteoporosis, and maintain methodologic standards to increase their use by decision-makers.

Background Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and is associated with an estimated annual fracture rate of 5%. We aimed to assess the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis. Methods We did a 24-month, double-blind, active-controlled, double-dummy, non-inferiority study at 79 centres in Europe, Latin America, Asia, and North America. Eligible patients were aged 18 years or older and were receiving glucocorticoids (>= 7.5 mg prednisone daily, or equivalent) for at least 3 months (glucocorticoid continuing) or less than 3 months (glucocorticoid initiating) before screening. Patients younger than 50 years needed to have a history of osteoporosis-related fracture; glucocorticoid-continuing patients aged 50 years or older needed a lumbar spine, total hip, or femoral neck bone mineral density T score of -2.0 or less, or -1.0 or less if they had a history of osteoporosis-related fracture. Participants were randomly assigned (1: 1) to either 60 mg subcutaneous denosumab every 6 months and oral placebo daily for 24 months, or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months. Randomisation was stratified by sex within each subpopulation, and was done with an interactive voice-response system. Active drugs and corresponding placebos had identical packaging, labels, and appearance. The primary outcome was non-inferiority of denosumab to risedronate in terms of percentage change from baseline in lumbar spine bone mineral density at 12 months based on non-inferiority margins (-0.7 and -1.1 percentage points for the glucocorticoid-continuing and glucocorticoid-initiating subpopulations, respectively). Superiority was also assessed as a secondary outcome. The primary efficacy set included all randomly assigned participants who had a baseline and postbaseline lumbar spine bone mineral density measurement, and was analysed according to randomised treatment assignment. The safety analysis set included all randomly assigned participants who received at least one dose of investigational product, and was analysed by actual treatment received. This study is registered with ClinicalTrials.gov (NCT01575873) and is completed. Findings Between March 28, 2012, and June 30, 2015, 795 patients, 505 of whom were glucocorticoid continuing and 290 of whom were glucocorticoid initiating, were enrolled and randomly assigned (398 to denosumab, 397 to risedronate). Denosumab was both non-inferior and superior to risedronate at 12 months for effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing (4.4% [95% CI 3.8-5.0] vs 2.3% [1.7-2.9]; p

Background:Patients (pts) with rheumatoid arthritis (RA) with poor prognostic factors (PPF) are at risk for RA progression if disease activity is not rapidly controlled. In FINCH 3 (NCT02886728), filgotinib (FIL)—an oral, potent, selective JAK1 inhibitor—was effective relative to methotrexate monotherapy (MTX mono) in MTX-naïve patients with ≥1 PPF—erosions, seropositivity for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP), or hsCRP ≥4 mg/L.1Objectives:This post hoc analysis examined FIL efficacy in FINCH 3 pts with multiple PPF.Methods:The global, phase 3, double-blind, active-controlled FINCH 3 study randomised MTX-naïve pts with moderately to severely active RA 2:1:1:2 to oral FIL 200 mg once daily + MTX ≤20 mg weekly, FIL 100 mg + MTX, FIL 200 mg mono, or PBO + MTX up to week (W)52. This subgroup analysis included pts with all 4 of the following PPF at baseline (PPF pts): erosions, seropositivity for RF or anti-CCP, hsCRP ≥4 mg/L, and DAS(28)CRP >5.1. Comparisons were not adjusted for multiplicity.Results:Of 1249 pts randomised and treated in FINCH 3, 510 had all 4 PPF. At baseline, relative to the overall FINCH 3 population, PPF pts had longer mean disease duration (2.4 vs 2.2 years); higher mean hsCRP (27.9 vs 17.5 mg/L), mTSS (17.9 vs 13.3), DAS28(CRP) (6.3 vs 5.7), HAQ-DI (1.76 vs 1.56), CDAI (44.3 vs 39.8), and SDAI (47.1 vs 41.5); and greater frequency of seropositivity for RF (90.6% vs 67.9%), anti-CCP (92.4% vs 68.5%), or both (82.9% vs 59.6%). Efficacy in PPF pts was comparable to data from all FINCH 3 pts (Table, Figures 1–2). PPF pts receiving FIL 200 mg with or without MTX vs MTX mono had higher frequencies of ACR20/50/70 response and greater improvement in HAQ-DI at W24; responses were numerically greater for FIL 200 mg + MTX vs FIL 100 mg + MTX or FIL 200 mg mono (Table) and were evident by W12 (data not shown). Radiographic progression at W24 was lower in PPF pts receiving FIL 200 mg + MTX or FIL 200 mg mono vs MTX mono (Figure 1). Proportions of PPF pts receiving FIL 200 mg with or without MTX who achieved DAS28(CRP) Table.Efficacy outcomes in patients with 4 PPF and all FINCH 3 patients at W24FIL 200 mg+ MTXFIL 100 mg+ MTXFIL 200 mg monoMTXmonoPPFAllPPFAllPPFAllPPFAlln1724168520787210166416ACR20, %85.5*81.0***83.580.2*81.678.174.771.4ACR50, %70.3***61.5***58.857.0**59.858.1**48.245.7ACR70, %54.1***43.8***37.640.1***43.7*40.0***28.326.0HAQ-DIa−1.2***−0.94***−1.0*−0.90**−1.0*−0.89*−0.9−0.79aMean change from baseline.*, p **, p ***, p FIL, filgotinib; mono, monotherapy; MTX, methotrexate; PPF, poor prognostic factors.Conclusion:FIL treatment provided rapid and deep disease control including higher rates of remission and other clinical outcomes, improved physical function, and less radiographic progression compared with MTX alone in MTX-naïve pts with RA with 4 PPF, a population at risk for severe progressive disease. In pts with 4 PPF, W24 remission rates following FIL 200 mg with or without MTX were higher vs MTX mono and numerically higher vs FIL 100 mg + MTX.References:[1]Westhovens et al.Ann Rheum Dis2019;78(Suppl2):259–60.Disclosure of Interests:Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Cecile Gaujoux-Viala Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Gilead Sciences, Inc.; Janssen; Lilly; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB, Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Gilead Sciences, Inc.; Janssen; Lilly; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB, Giovanni Adami: None declared, Alan Matsumoto Grant/research support from: AbbVie; BMS; Eli Lilly; Galapagos; Gilead Sciences, Inc.; GSK; Janssen; Novartis; Pfizer; Sanofi; UCB; Regeneron, Consultant of: AbbVie; Gilead Sciences, Inc.; GSK; Novartis, Paul Bird Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer – advisor, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Osvaldo Messina Speakers bureau: Amgen; Americas Health Foundation; Pfizer, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Thijs Hendrikx Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma

Introduction. An intimate relationship between osteoporosis and sarcopenia has been established. At present, there are few epidemiological studies about osteosarcopenia due to the recent use of this term, especially in Latin America. Objective. To study the association between osteoporosis and sarcopenia and determine the prevalence of osteosarcopenia in patients who attended a rheumatology center in Ecuador. Methods. A cross-sectional study was conducted in a population of patients who had a densitometric study. The diagnosis of sarcopenia was determined by the DXA standard gold test, screening, and conventional methods (bioimpedance, anthropometric measurements, SARC-F, muscle function, and gait test). Results. A total of 92 patients were studied. The median age was 66 ± 10, 90% females. Using the criteria of SMI, 65% had sarcopenia of which 9% had only sarcopenia and 56% had osteosarcopenia; 22% had only osteopenia/osteoporosis; and 13% none of these conditions. The prevalence of sarcopenia according to handgrip strength was 60%, gait speed 45%, and SARC-F score 40%. The prevalence of osteosarcopenia according to handgrip strength was 51%, gait speed 34%, and SARC-F score 32%. Osteoporosis was associated with a higher prevalence of sarcopenia using the criteria of SMI since 40% had sarcopenia in the normal DXA group, 64% in the osteopenia group, and 76% in the osteoporosis group (p=0.017). Of the women, 69% had sarcopenia compared to 33% of the men (p=0.034). The BMI was lower in the group with sarcopenia (25.1 ± 4.1 kg/m2) compared to the group without sarcopenia (29.4 ± 4.1 kg/m2, p<0.001). Patients with osteosarcopenia and sarcopenia had lower BMI, handgrip strength, ASM, SMI, and total-body skeletal muscle mass than those with osteopenia/osteoporosis or normal patients. Conclusion. 65% of the studied population had sarcopenia. It is clear that the prevalence of sarcopenia is higher in patients with greater loss of bone mass. Identifying pathways that affect both bone and muscle could facilitate the development of treatments that simultaneously improve osteoporosis and sarcopenia.

Background In a study of patients initiating or continuing GC, 12 and 24 months gains in lumbar spine and total hip areal bone mineral density (aBMD) were greater with DMAb vs RIS.1,2 Objectives Evaluate the effects of DMAb vs RIS on cortical and trabecular bone. Methods Phase 3, double-blind, double-dummy, active-controlled study randomised women and men ≥18 years, receiving GC (≥7.5 mg prednisone daily or equivalent) for Results The substudy enrolled 111 subjects (57 DMAb, 54 RIS). DMAb was associated with significantly greater increases than RIS in cortical thickness, total volumetric BMD (vBMD) and cortical vBMD at the radius and tibia at 12 and 24 months, and in trabecular vBMD at the radius at 12 months and tibia at 24 months (Table). Change in cortical porosity did not differ between DMAb and RIS (Table). Percentage Change From Baseline and Treatment Difference in vBMD and Cortical Microarchitecture Conclusion Compared with RIS, DMAb was associated with sustained improvements in cortical bone structure, assessed by HR–pQCT of the radius and tibia. It remains to be confirmed whether increased cortical thickness with DMAb is associated with improved bone strength in GIOP. These results further support DMAb as a treatment for GC-treated patients at increased fracture risk. References [1] Saag KG, et al. Lancet Diabetes Endocrinol. 2018;6(6) [2] Saag KG, et al. Ann Rheum Dis. 2018;77 (Suppl 2) Acknowledgement This study was funded by Amgen Inc. Disclosure of Interests Piet Geusens Grant/research support from: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Consultant for: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Stefan Goemaere Grant/research support from: Grants/research funding from Amgen, UCB., Speakers bureau: Speakers’ bureau for Amgen., Nicola Pannacciulli Shareholder of: Amgen Inc. stockholder., Employee of: Amgen Inc. employee at the time of the study., Nancy Lane Consultant for: Samumed, LLC, Eric Lespessailles Grant/research support from: Grants/research support from Amgen, Eli Lily, MSD, UCB., Consultant for: Consultant for Amgen, Expanscience, Eli Lilly, MSD, UCB., Osvaldo Messina Consultant for: Consultant for Eli Lily, Amgen, Pfizer., Speakers bureau: Speakers’ bureau for Eli Lily, Amgen, Pfizer., Roland Chapurlat Grant/research support from: Grants/research support from Amgen, Roche-Chugai, MSD., Consultant for: Consultant for Amgen, UCB, Pfizer, Bristol-Myers Squibb, Sandoz, Radius., Speakers bureau: Speakers fees for Eli Lily, Pfizer, Abbvie, MSD, Janssen-Cilag., Xiang Yin Shareholder of: Amgen Inc. stockholder., Employee of: Amgen Inc. employee at the time of the study., Rachel Wagman Shareholder of: Amgen Inc. stockholder., Employee of: Amgen Inc. employee., Joop van den bergh Grant/research support from: Grants/research support from Eli Lily, Sanofi, Amgen.

In the published article the author name Maritza Vidal Wilman was processed incorrectly and now it has been rectified. The original article has been updated.

Background:Infectious diseases are increased in patients with rheumatic disorders; vaccination improves morbidity and mortalityObjectives:The aim of this study was to describe the frequency of vaccination in patients with rheumatic disorders and to compare the results with those obtained in 2009 and 2013 in a similar population. We also identified factors leading to lack of vaccination and patients beliefs on vaccines.Methods:Multicentric cross sectional study in patients with autoinmune diseases from external rheumatology offices. Evaluation of vaccination status and patients´ knowledge about vaccines were studied. A comparative analysis was carried out with the series registered in 2009 and 2013 in a similar population.Results:179 patients (158 female, 88.3% and 21 male, 11.7%) were evaluated. Median age was 52 years. Main pathologies were: Rheumatoid Arthritis 65.9% (n:118), Systemic Lupus Erythematosus 11.7% (n:21), Systemic Sclerosis 3.9% (7), Sjogren Syndrome n = 3.4% (n:6), other diseases 15% (n: 27). Median disease duration: 8.87 years. Ninety three percent of patients (n:167) were taking inmunomodulators and 36.8% (n: 66) were using oral corticosteroids (20mg/day or less); 26,8% patients (n: 48) were receiving biological therapies. Vaccination frequency in the population was: Influenza 82% (147); 13-valent conjugate pneumococcal 69.3% (124), 23-valent pneumococcal 64.2% (115) and hepatitis B 62% (111). Comparative with 2009 and 2013 series there was an increase in the rate of vaccinated patients: influenza (82% vs. 39,1% and 74,2% respectively), antineumococcal (64% vs. 17% and 29%) and hepatitis B (62% vs. 6,7% and 26,7%).Reasons for non-vaccination were absence of medical indication (41% of patients for hepatitis B; 32% for 23-valent pneumococcal; 38% for 13-valent pneumococcal and 34% for influenza).139 patients (77, 7%) knew the benefits of vaccines, 164 (91, 6%) thought vaccines are useful; 134 (74,9%) reported that vaccines may decrease dying probability, 155 (86,5%) thought that vaccines are effective to prevent diseases and 149 patients (83,2%) believed that they prevent serious infections. 71 patients (39%) believed that vaccines can lead to serious consequences and 99 (55,3%) that they are more likely to acquire infections than the rest of the population.Conclusion:Frequency of vaccination has increased since 2009 but there is still misinformation regarding vaccines risks and benefits. Promotion and information is essential to improve adherence.References:[1]2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Furer V, et al. Ann Rheum Dis 2020;79:39–52[2] Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist. Friedman MA et al. Rheum Dis Clin North Am. 2017 Feb; 43 (1):1-13.[3] Recommendations and barriers to vaccination in systemic lupus erythematosus. Garg M et al. Autoimmun Rev. 2018 Oct; 17 (10):990-1001.[4] Comparison of national clinical practice guidelines and recommendations on vaccination of adult patients with autoimmune rheumatic diseases. Papadopoulou D. et al. Rheumatol Int. 2014 Feb;34 (2):151-63.[5] Guías de recomendaciones de prevención de infecciones en pacientes que reciben modificadores de la respuesta biológica. Jordán R. Et al. Rev Arg Reumatol. 2014; 25 (2): 08-26.Disclosure of Interests:Malena Viola: None declared, Alejandro Benitez: None declared, Cecilia Garbarino: None declared, Gonzalo Rodriguez: None declared, Federico Benavidez: None declared, Claudia Peon: None declared, Eliana Soledad Blanco: None declared, Hernan Molina: None declared, Gimena Gómez: None declared, griselda redondo: None declared, Maria DeLaVega: None declared, Dario Mata: None declared, Augusto Riopedre: None declared, Osvaldo Messina Speakers bureau: Amgen; Americas Health Foundation; Pfizer

Background Osteoporosis is a common disorder affecting populations worldwide. In Latin America, an aging population combined with limited health care resources result in osteoporosis quickly becoming a condition of considerable magnitude with disproportionate morbidity and mortality. Aim To review the current state of prevention, diagnosis, and treatment of osteoporosis in Latin America and to develop strategies and recommendations that may be adopted in the region, an expert panel of clinicians and scientists was assembled to develop a consensus statement outlining future directions. Method The panel conducted a comprehensive literature review of publications mainly related to osteoporosis in Latin America, and at an in-person meeting developed a consensus position to address the relevant issues. Results The epidemiology, burden, diagnosis, and treatment of osteoporosis in the region were discussed with particular attention to issues unique to the region. A series of recommendations were developed encompassing virtually all aspects of the disease, including improved public and health professional awareness, better diagnostic processes, improved access to care, and greater engagement by health policy makers, government, and a wide variety of private organizations. Conclusions The panel concluded that a comprehensive approach to osteoporosis prevention and treatment in Latin America is urgently needed.

Background Denosumab 60 mg subcutaneously Q6M increased spine and hip BMD significantly more than risedronate 5 mg orally QD at 12 months in glucocorticoid-treated subjects (as previously reported¹). Objectives This analysis compared the BMD effects of denosumab vs risedronate and further characterised denosumab safety in this population at 24 months. Methods This phase 3, randomised, double-blind, double-dummy study enrolled adults≥18 years receiving ≥7.5 mg daily prednisone (or equivalent) for Results Of 795 randomised subjects, 590 (74.2%) completed the 24 month study (glucocorticoid-initiating: 109/145 denosumab, 117/145 risedronate; glucocorticoid-continuing: 186/253 denosumab, 178/252 risedronate). Denosumab was superior to risedronate for increases from baseline in LS and TH BMD at all timepoints assessed through 24 months in each subpopulation (figure 1). Adverse events, serious adverse events (including infection), and fractures were similar between groups. Conclusions In conclusion, denosumab was superior to risedronate for increases in spine and hip BMD through 24 months. The overall safety profile was similar between groups. Denosumab may offer a valuable osteoporosis treatment option for patients receiving glucocorticoids. Reference [1] Saag K, Wagman RB, Geusens P, et al. Effect of denosumab compared with risedronate in glucocorticoid-treated individuals: Results from the 12-month primary analysis of a randomized, double-blind, active-controlled study. Ann Rheum Dis2017:76(Suppl 2):54. Acknowledgements This study was funded by Amgen Inc. Jonathan Latham (PharmaScribe, LLC) and Lisa Humphries (Amgen Inc.) provided medical writing support. Disclosure of Interest K. Saag Grant/research support from: Amgen, Merck, Consultant for: Amgen, Lilly, Merck, Radius, N. Pannacciulli Shareholder of: Amgen, Employee of: Amgen, P. Geusens Grant/research support from: Abbott, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Will-Pharma, Consultant for: Amgen, Lilly, J. Adachi Grant/research support from: Amgen, Consultant for: Amgen, Employee of: McMaster University, Speakers bureau: Amgen, O. Messina: None declared, J. Morales-Torres Consultant for: Amgen, Speakers bureau: Amgen, R. Emkey Speakers bureau: Amgen, P. Butler Shareholder of: Amgen, Employee of: Amgen, X. Yin Shareholder of: Amgen, Employee of: Amgen, W. Lems Consultant for: Amgen, Eli Lilly, Merck, Speakers bureau: Amgen, Eli Lilly, Merck

Objective.To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America.Methods.Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history.Results.Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment.Conclusion.Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Background Glucocorticoid (GC)-induced osteoporosis (GIOP) remains the most common secondary cause of osteoporosis. Despite approved therapies, many subjects do not receive GIOP prevention or treatment. There is increased RANKL and decreased osteoprotegerin (OPG) expression in patients with GIOP. Denosumab (DMAb) is a monoclonal antibody to RANKL. This study was designed to assess the safety and efficacy of DMAb compared with risedronate (RIS) in GC-treated individuals, in whom treatment guidelines advocate a GIOP intervention. Objectives The primary objective was to demonstrate, in separate GC-continuing (GC-C) and GC-initiating (GC-I) subpopulations, that DMAb was not inferior to RIS with respect to percentage change from baseline (%Δ) in lumbar spine (LS) bone mineral density (BMD) at 12 months. Secondary objectives were to assess superiority of DMAb over RIS with respect to %Δ in LS and total hip (TH) BMD at 12 months. Methods This was a phase 3, randomized, double-blind, double-dummy, active-controlled study to evaluate DMAb vs. RIS in GC-treated individuals for 24 months. Eligible subjects were women and men ≥18 yrs receiving GC therapy at a dose ≥7.5 mg prednisone daily or its equivalent for ≥3 months or Results A total of 795 subjects (505 GC-C and 290 GC-I) enrolled in the study. Baseline characteristics were balanced between treatment groups (Table). Non-inferiority and superiority with DMAb were demonstrated for both the GC-C and GC-I subpopulations, as indicated by significantly greater BMD gains compared with RIS at the LS and TH in both subpopulations (Figure). The incidences of adverse events (AEs) and serious AEs, including serious AEs of infection, as well as fracture, were similar between treatment groups and consistent with the known safety profile of DMAb. Conclusions DMAb significantly increased BMD more than RIS at the spine and hip at 12 months. The overall safety profile was similar between treatment groups. DMAb has the potential to become another treatment option for patients newly initiating or continuing GC who are at risk for fracture. Acknowledgements The study was funded by Amgen. C Desborough (Amgen [Europe] GmbH) provided editorial support. Disclosure of Interest K. Saag Grant/research support from: Amgen, Merck, Consultant for: Amgen, Merck, Radius, R. B. Wagman Shareholder of: Amgen, Employee of: Amgen, P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Roche, UCB, BMS, Novartis, J. Adachi Grant/research support from: Amgen, Eli Lilly, Merck, Pfizer, Consultant for: Amgen, Eli Lilly, Merck, International Osteoporosis Foundation, Speakers bureau: Amgen, Eli Lilly, O. Messina Grant/research support from: Amgen, GSK, R. Emkey Speakers bureau: Amgen, R. Chapurlat Grant/research support from: Amgen, Merck, Chugai, Consultant for: Amgen, Eli Lilly, BMS, AbbVie, Pfizer, Chugai, UCB, N. Daizadeh Shareholder of: Amgen, Employee of: Amgen, N. Pannacciulli Shareholder of: Amgen, Employee of: Amgen, W. Lems Grant/research support from: Eli Lilly, Amgen, MSD, Novartis.

INTRODUCTION: Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.METHODS: Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents."CONCLUSION: Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.

Background Endovascular interventions are increasing; however, there are little data regarding outcomes of complex interventions involving the below-knee popliteal/P3 artery. This study evaluated the short-term and long-term results and predictors of success of below-knee popliteal artery endovascular interventions. Methods This was a retrospective review of a prospectively maintained endovascular lower extremity database of all patients with below-knee popliteal interventions from 2004 to 2012. Patient demographics, angiographic findings, interventions, primary and secondary patency, limb loss, and mortality were recorded. Analysis was performed using Kaplan-Meier life-table and multivariate analysis, with P Results There were 221 patients (56% male) with below-knee popliteal/P3 artery lesions. Mean age was 73 ± 11.2 years. Claudication was present in 22% and critical limb ischemia (CLI) in 78%. Mean lesion length was 10 ± 8.5 cm, with 45% having total occlusions. Treatment included percutaneous transluminal angioplasty (PTA) with or without a stent (47%), atherectomy (ATH) with or without PTA/stent (52%), and stenting with PTA and ATH (3%). Complications included embolization (0.4%), hematoma (2.7%), pseudoaneurysm (1.3%), and dissection (7%). Freedom from restenosis (peak systolic velocity ratio >2.4) was 65% at 1 year. Independent predictors of restenosis were CLI (hazard risk [HR], 4.4; 95% confidence interval [CI], 1.9-9.9) and stenting combined with PTA and ATH (HR, 2.7; 95% CI, 1.01-7.4). Primary assisted and secondary patencies were 95% and 85% at 1 year. ATH with PTA had lower short-term restenosis in diabetic patients compared with nondiabetic patients (95% vs 78% at 4 months). Limb loss was 18% at 4 years. Mortality was 24% at 4 years. Statin use was protective against primary restenosis (HR, 0.39; 95% CI, 0.23-0.67) and death (HR, 0.5; 95% CI, 0.28-1.0). Conclusions Endovascular intervention for lesions involving the below-knee popliteal artery is a safe and effective therapy for claudication and CLI. Diabetic patients benefit most from ATH with PTA. Statin use is protective against restenosis and mortality and should be the standard of care in patients undergoing peripheral endovascular interventions.

Osteoporosis is a generalized disease of bone that increases fracture risk. Multiple factors influence this risk, besides low bone mass. To decrease osteoporotic fractures, those patients who require preventive management should be readily identified. This paper aims to review current information on the use of the fracture risk assessment tool (FRAX™) in Latin America. Bone mineral density measurement is currently the method of reference for evaluating the fracture risk and opting for treatment; but, it misses a notable proportion of individuals who have clinical risk factors for osteoporosis and fractures. FRAX™ was designed to predict the 10-year absolute risk of sustaining a major osteoporotic fracture or a hip fracture. Although data is available for several countries, from Latin America, only Argentina appears in the current version of the tool. Its present use in other Latin American countries is possible with some adaptations based in similarities of epidemiological information of each country with some of the existing databases. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations.

Objective . To assess the transcultural equivalency of the Spanish version of the Fibromyalgia Rapid Screening Tool (FiRST) and its discriminatory ability in different Latin American samples. Design . Validation study. Setting . Departments of Rheumatology in general hospitals and private centers; fibromyalgia unit in a university hospital. Subjects . 350 chronic pain patients from Spain, Argentina, Mexico, Peru, and Ecuador. Methods . The cultural relevance of the Spanish version of the FiRST was evaluated. The ability of the FiRST as a screening tool for fibromyalgia was assessed by logistic regression analysis. To determine the degree to which potential confounders, such as differences in demographics, pain, affective distress, catastrophizing, and disability, might affect the discriminatory ability, the tool was reassessed by hierarchical multivariate logistic regression. Results . Slightly different versions of the FiRST were recommended for use in each Latin American subsample. The FiRST showed acceptable criterion validity and was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, low specificities were observed in samples from Spain and Mexico. Conclusions . The Spanish version of the FiRST may be used as a screening tool for fibromyalgia in several Latin American subsamples, even in those patients with high scores on potential confounders. In Spain and Mexico, the low specificity of the FiRST suggests, however, that it would be best used to support a suspected diagnosis of fibromyalgia, rather than to exclude the diagnosis.

Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p < 0.001) and femoral neck (+3.2%; p < 0.002) versus basal level, whereas the calcium only group failed to exhibit significant differences. The entire 60-strong population was then split into two groups, according to whether individual BMD content was greater or less than the mean basal value for each skeletal site evaluated. For either treatment, subpopulations with lower basal BMD tended to achieve greater bone gain, though statistically significant differences were only disclosed at trochanter (p < 0.004) with APD and at femoral neck (p < 0.002) in the calcium only group. Globally speaking, increases in BMD were observed in 60-80% of patients receiving either treatment - who were thus defined as responders - at each particular skeletal area assessed. However, when only skeletal areas with low basal BMD were considered, the number of responders reached 60-100%. Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those relitively spared by the course of the disease.

Objective. Despite showing acceptable psychometric properties, the criterion validity of the original Fibromyalgia Rapid Screening Tool (FiRST) has been called into question for including insufficiently challenging comparison groups. Consequently our objective was to validate a Spanish version of the FiRST including pain disorders more analogous to fibromyalgia. Methods. The FiRST was translated following international standards. Internal consistency and temporal stability were assessed. The ability of the FiRST global score as a screening tool for fibromyalgia (criterion validity) was assessed by logistic regression analysis. To determine the degree to which potential confounders might affect the criterion validity of the FiRST (divergent validity), it was reassessed by hierarchical multivariate logistic regression, entering demographics in a first step, followed by pain, anxiety and depression, catastrophizing, disability and the FiRST global score in a last step. Results. The final sample comprised 257 patients (67% cases of fibromyalgia). The Spanish version of the FiRST showed acceptable internal consistency, reliability and criterion validity. The FiRST was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, both criterion and divergent validity were challenged by a moderate specificity. Conclusion. The Spanish version of the FiRST may be used as a screening tool for fibromyalgia even in those patients whose cognitive style is characterized by catastrophizing about pain and high levels of functional disability, anxiety and depression. The clinical consequences of the moderate specificity shown by this Spanish version of the FiRST are discussed.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF–ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

UNLABELLED: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. INTRODUCTION: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. METHODS AND RESULTS: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. CONCLUSIONS: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. Relationships between immunohistochemical data and clinicopathological characteristics were investigated using the Chi-square test; the cohort was analysed with respect to pT1a and pT1b BC as well as to node status. Ductal infiltrating carcinoma was the prevalent histotype in the pT1a and pT1b stages; G2 was a more common tumour grade, with a range between 64.6% and 70% of pT1a and pT1b, respectively. Taking into consideration the lymph node involvement of pT1a,b BC, only 17.1% cases were node-positive without a relevant difference between pT1a and pT1b. No significant differences between pT1a and pT1b BC cases emerged in relation to Ki67 LI, hormone receptors and HER2 status. T1a,b BC cases were stratified by node involvement and a significant relationship was observed with grade as well as with HER2 status. A significant relationship for pT1a cases emerged only for tumour grade, while pT1b cases showed a significant correlation exclusively with HER2 status. Our data clearly support the operative guidelines of the National Comprehensive Cancer Network. Therefore, the combined treatment with trastuzumab plus chemotherapy should be administered only to patients with pT1b or larger BCs. In small HER2-positive pT1a or microinvasive BC, this therapy should be considered on a case-by-case basis, considering tumour grade as the first characteristic.

The objective of this study was to assess the prevalence of rheumatoid arthritis (RA) in the population of a city of 70,000 inhabitants located in Buenos Aires, Argentina.Based on the hypothesis that RA is an underdiagnosed disease in Argentina, a capture-recapture method was applied. A local registry of RA patients of Luján City was taken as the primary source; a telephone survey was specifically carried out as a secondary source of information. Patients suspected of having RA were referred to a local hospital to be examined by a team of 12 rheumatologists. Anamnesis and physical examination were followed by hand and foot radiography and erythrocyte sedimentation rate and rheumatoid factor measurements.According to the American College of Rheumatology criteria, a prevalence rate of 0.94% (95% confidence interval [CI], 0.86%-1.02%) was found in the surveyed population; in agreement with other studies, this prevalence was higher in women when compared with men (for female, 1.54% [95% CI, 1.40%-1.69%]; for male, 0.40% [95% CI, 0.32%-0.49%]).The prevalence of RA in a representative sample of the population of a city from the central region of Argentina seems to be close to 1%.

To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scoresor=-2.5) in Latin America.Retrospective study involving review of medical records.Osteoporosis clinics in 6 Latin American countries.Postmenopausal women agesor=50 in Latin America who had femoral neck BMD measurements.A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index=-2; 65.6% were osteoporotic), moderate-risk patients (-2index=1; 26.7% were osteoporotic), and low-risk patients (index1; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil.Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.

Background Fibromyalgia syndrome (FM) requires an expert clinical examination that impedes an easy assessment of diagnostic criteria in some health settings. This problem delays its diagnostic, treatment and referral to specialized services1,2. To solve this drawback, a new screening test, the Fibromyalgia Rapid Screening Tool (FiRST) was created3. Despite showing acceptable psychometric properties, notably independent of depression, anxiety, catastrophizing and functional disability, the validation of the FiRST has been questioned for including non-challenging comparators and excluding patients with a severe depression4. Objectives To validate a Spanish version of the FiRST including pain disorders more analogous to fibromyalgia Methods The FiRST was translated following international standards. Internal consistency and temporal stability were assessed. The ability of the FiRST global score as a screening tool for fibromyalgia (discriminant validity) was assessed by logistic regression analysis. To assess to what degree potential confounders might affect the discriminant validity of the FiRST (divergent validity), it was re-assessed by hierarchical multivariate logistic regression with demographics in a first step, followed by pain, anxiety and depression, catastrophizing, disability, and the FiRST global score in a last step. Results The final sample comprised 257 patients (67% cases of fibromyalgia). The Spanish version of the FiRST showed acceptable internal consistency, reliability, and discriminant validity. The FiRST was able to discriminate between fibromyalgia and non-fibromyalgia patients even after discarding the effect of potential confounders. Both discriminant and divergent validity were, however, challenged by a moderate specificity (55% of non-fibromyalgia patients correctly classified). Conclusions The Spanish version of the FiRST may be used as a screening tool for fibromyalgia even in those patients that present with psychopathology, a cognitive style characterized by catastrophizing about pain and high levels of functional disability. The moderate specificity of the Spanish version of the FiRST suggests that, in its current form, it must be better used to rule in a fibromyalgia rather than to rule it out. References Annemans L, Wessely S, Spaepen E, Caekelbergh K, Caubere JP, Le Lay K et al. Health economic consequences related to the diagnosis of fibromyalgia syndrome. Arthritis Rheum 2008; 58(3):895-902. Choy E, Perrot S, Leon T, Kaplan J, Petersel D, Ginovker A et al. A patient survey of the impact of fibromyalgia and the journey to diagnosis. BMC Health Serv Res 2010; 10:102. Perrot S, Bouhassira D, Fermanian J. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain 2010; 150(2):250-256. Hansson PT. Yet another questionnaire is born! Pain 2010; 150(2):219. Disclosure of Interest None Declared

Background Fibromyalgia (FM) is a common condition in young and middle-aged women, which is mainly characterized by diffuse chronic pain and is associated with other manifestations such as fatigue, unrefreshing sleep, stiffness, anxiety and depresion1. Recent studies have evaluated that chronic pain syndrome and related manifestations could have a negative impact on sexual function of these patients, as well as psycho-physical abuse history could act as potential triggers of FM. Objectives Assess sexual function in women with FM and correlate with tender points count, clinical severity, anxiety, depression, chronic fatigue and history of physical and psychological violence. Methods A case-control study. Between 03/01/12 and 06/30/12 were included consecutively: women >18 years diagnosed with FM according to ACR criteria 990, and healthy controls >18 years, without history of violence. We excluded patients with other causes of chronic pain disorders and psychotic disorders. We recorded: sociodemographic data, education, employment and menopausal status and sexual function by Female SexualFunction Index2 (FSFI: self-administered questionnaire that assesses six domains: desire, arousal, lubrication, orgasm, satisfaction and pain). In the FM group tender points count, duration of disease, medication, psychological care, presence of chronic fatigue (by Fukuda Criteria), clinical severity (FIQ-Spanish version), depression (HADS), and history of physical or psychological violence (Screening Questionnaire of Violence)3 were assessed. We used Chi2 test, Student t test and Mann-Whitney test, and Spearman correlation coefficient (significant p ≤ 0.05). Results We included 52 patients in the FM group and 52 in the control group. Median age: 50 ± 9.2 and 47 ± 10 years, respectively. FM Group: Medium evolution time: 60 months, mean pain points: 15 ± 3, FIQ median: 67.8 (28-86). 73.1% received medication for FM and 44.2% demanded psychological care. We found significant impaired sexual function vs controls (median FSFI total: 17.2 (1.2-33.3) vs. 29.4 (1.2-36), p Conclusions Our patients with FM had impaired sexual function compared to control group. Physical and psychological violence were frequent but weren´t related with sexuality function. References Kalichman L. Association Between Sexual Dysfunction and FM. Clinical Rheum 2009, 28: 365-69. Blumel JE, Binfa LE, Cataldo PA, Carrasco AV. Female Sexual Function Index: a test to assess women’s sexuality. Rev Chil. Obstetrics Gynecol 2004; 69 (2): 118-125. Tavara-Orozco L, Zegarra-Samame Turra, Ceiso Zelaya. Screening Gender Violence: three services reproductive health care. Ginecol. Obstet (Peru) 2003, 49 (1): 31-38. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality due to myocardial infarction, stroke and heart failure. Both, chronic inflammation leading to arterial stiffness, and some of the drugs used to treat RA, such as corticosteroids and leflunomide, are risk factors for developing arterial hypertension (HT). Objectives The aim of this study is to determine the prevalence of HT in outpatients with RA at a rheumatology office in Buenos Aires, and describe their relationship with clinical, laboratory and disease activity Methods We evaluated consecutive outpatients with a diagnosis of RA according ACR 90 criteria that attend to the Rheumatology office of a public hospital in Buenos Aires. Blood pressure (BP) was assessed by 3 protocolized measurements, clinical data was collected and disease activity was evaluated by DAS28-ESD. Statistical analysis was performed to establish prevalence of hypertension and to establish association with clinical and laboratory variables using Mann Whitney and Chi Square test. Significance was p≤0.05. Results We analyzed 99 patients (85.9% female and 14.1% male) with a mean age of 51.3 years old (range 26-80). 79.8% had Functional Class I and II. The prevalence of hypertension in our population was 50.5%. The median time to progression of RA: 9.57 years, DAS 28: 4.06 (range: 1.54 to 7.55), 65.7% of individuals take corticosteroids. HT was associated with age (56.16 years (26-80) the HT patients versus 46.35 years (26-81) for non HT patients(p Conclusions Almost a half of RA patients had blood hypertension at the medical office during a standard control. It was significantly related to age and abdominal diameter. It was higher than the prevalence for the general population of Buenos Aires References Solomon D, Karlson E, Rimm E, Cannuscio C, Mandl M. Cardiovascular morbidity and mortality in women diagnosed with Rheumatoid arthritis. Circulation 2003;107:1303–7. Ferrante D, Virgolini M. Encuesta Nacional de Factores de Riesgo 2005: resultados prinicpales. Prevalencia de factores de riesgo de enfermedades cardiovasculares en la Argentina. Rev. Argent Cardiol. 2007; 75; 20-29. Hernandez- Hernandez R, Silva H, Velasco M, et al. Hypertension in seven Latin American cities: the cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study. J. Hypertens 2010; 28; 24-34. Panoulas V, et. al. Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology 2007;46:1477–1482 Disclosure of Interest None Declared

The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater V ss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the C max was 20 times lower than the C 0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t 1/2β ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the V ss and WBR were significantly correlated with serum alkaline phosphatase levels and the V ss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t 1/2β after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher V ss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

Aim: To examine the efficacy of lifestyle intervention on obese children and adolescents (6—16 years) at Princess Margaret Hospital, Western Australia. Strict inclusion criteria exists for this intervention so that participants have significant obesity or obesity with co morbidities. Method: A 12-month group-based multidisciplinary lifestyle programme was attended by 114 subjects (February 2008—May 2011). Anthropometry and cardio-metabolic parameters were assessed at baseline, 10 weeks and 12 months. Non-parametric Wilcoxon signed ranked test was used to test for improvement between pre-treatment and post-treatment parameters. Results: 114 patients were available for analysis (58% female; 44%children

Fifteen patients with adult onset Still's disease are described, all diagnosed according to recognized criteria. Mean delay in reaching a firm diagnosis was 16 months. Besides the typical clinical picture, there was a high frequency of pruriginous rash, one instance of overlapping polymyositis and recurrent systemic manifestations in most cases. Chronic polyarticular involvement predominated, with radiological progression particularly in wrist, proximal interphalangeal and hip joints. However, functional prognosis at the end of a mean 4.8-year course was satisfactory, as also the response to treatment mainly with steroid drugs and, on occasion, with remitting agents to alleviate arthritis.

Background: The delay between onset of symptoms and coronary care unit admission is decisive in the outcome of patients with acute myocardial infarction. Objective: To evaluate the influence of the factors that affect the delay in acute myocardial infarction treatment. Methods: Multicenter case-control study conducted by 118 coronary care units in Italy. The median and mean times in cases and controls were compared for decision time, home-to-hospital time, and in-hospital time, and the influence of several potential risk factors on the delay was evaluated by comparison of patients admitted more than 6 hours after onset with those admitted within 6 hours after onset. Results: Among 5301 patients with acute myocardial infarction, 590 who came to a coronary care unit after 12 hours were considered cases. Controls included 600 patients treated within 2 hours, 603 between 2 and 6 hours, and 466 between 6 and 12 hours. The median decision time among cases was 50-fold higher than that of controls who presented within 2 hours. Home-to-hospital time and in-hospital time appeared to play a less important role. Among the patient-related variables, advanced age, living alone, low intensity of initial symptoms, history of diabetes, strong pain at onset of the infarction, occurrence of symptoms at night, and involvement of a general practitioner seemed to affect delay significantly. Conclusion: Interventions aimed at reducing the delay in acute myocardial infarction treatment should primarily focus on the help-seeking behavior of patients. (Arch Intern Med. 1995;155:1481-1488)

The cerebrospinal fluid level of homovanilic acid (HVA), 5 hydroxyindolacetic acid (5HIAA) and 3 methoxy-4-hydroxy phenylglycol (MHPG) was determined twice at 12 to 15-day intervals in 23 patients with Alzheimer-type dementia (ATD). No correlation was found with the degree of dementia as assessed by psychometric testing. In most of the patients, the CSF levels of 5HIAA, MHPG and to a lesser extent HVA were found to be rather stable within a period of 2 weeks. The observation of a decrease in the concentration of HVA but not of 5HIAA or MHPG in 10 out of 12 patients treated with ergoloid mesylate may therefore be of interest in elucidating the mechanism of action of this drug in ATD.

Phonocardiography has been proved to be a very useful tool in cardiac diagnosis. Although by this method a good knowledge of acoustic phenomena of the heart has been achieved in the last twenty years, many problems still await solution. Thus, technical improvements in recording and filtration systems have been devised recently for a more nearly correct analysis of heart sounds and murmurs. A better approach to some clinical problems seems to be via intracardiac and direct epicardial phonocardiography. While the first method has been developed fully by several authors, the second, which was employed as early as 1917, by Wiggers and Dean, 1 has since been applied only in animals. 2–4 The opening of the epicardial sac, as is usually done during heart surgery in man, has offered us an opportunity for the application of the second method in human beings. This study was planned with the hope that by recording the heart sounds and murmurs directly from the epicardial surface of the various chambers of the heart, valuable information could be obtained about the transmission and diffusion of acoustic phenomena and the site of origin of still ill-defined murmurs. Some partial results have been published already elsewhere. 5,6

We discuss the clinical and serologic features of 27 patients with overlap syndrome followed prospectively by our group. The findings are similar to those of other reports, but we have drawn attention to the presence of peritendinous nodules in these patients and mentioned some peculiar neurologic manifestations. Rheumatoid arthritis was the most common diagnosis in our patients. The presence of high-titer antibodies against the nuclear ribonucleoprotein fraction of extractable nuclear antigen (nRNP) did not allow the identification of a particular subgroup. However, patients with this antibody tended to fulfill more criteria of more diseases than those without it. The findings lead us to conclude that antibodies to nRNP do not identify a particular subgroup within the overlap syndromes and that mixed connective tissue disease does not appear to be a distinct entity.