tbuckley/cabot-search huggingface dataset:
SAT0403 Arterial hypertension in patients with ankylosing spondylitis and psoriatic arthritis – results of 10-years follow-up
Authors: IZ Gaydukova, A Aparkina, E Kchondkaryan, A Rebrov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spondyloarthritis (SpA) (ankylosing spondylitis (AS) and psoriatic arthritis (PsA)) are associated with increased cardiovascular risk [1]. Destabilization of arterial pressure in chronic inflammation and anti-inflammatory treatment could be one of the reasons of early cardiovascular events onset. <h3>Objectives</h3> The purpose of this work is evaluate the occurrence and risk of arterial hypertension (AH) onset in patients with AS and PsA. <h3>Methods</h3> 663 patients were involved in the study: AS patients fulfilled mNew-York criteria (1984), PsA patients fulfilled CASPAR criteria (2006). Study included cross-sectional analyze, where 159 AS and 85 PsA patients participated, and 10-year prospective follow-up part, included 278 AS patients, 109 PsA patients. 276 patients were excluded due to lose the follow-up. In follow-up part of the study were involved SpA patients without AH at baseline. 182 healthy volunteers participated in the study like controls, 32 of them lost the follow-up. New cases of AH were registered after 4 and 10 years. Statistics was performed in SPSS17 and GraphPadPrizm. All the results were adjusted to cardiovascular risk factors. <h3>Results</h3> Characteristics of the patients and controls with 10-years follow-up are presented in table 1. 100% of patients recieved NSAIDs, 10% - glucocorticoids (5–10 mg prednisolone), 68.8% of PsA patients recieved methotrexate (10–25 mg/week), 14.3 of AS patients - sulfasalazine (2.0–3.0 g/day). Due to cross-sectional analyses was shown that AH occurred in 48.7 of AS and in 67.5% of PsA patients, respectively, p=0.03. Numbers of new AH cases during follow-up are presented in table 2. The relative risk (RR) of AH onset in patients with AS compared to healthy individuals is 2.22 (95% confidential interval (CI) 1.59 - 3.1); RR in PsA patients is 3.08 (95% CI 2.19 - 4.03), difference between risk of AH development in PsA and AS is significant, p&lt;0.0001. Median to new AH cases in AS and PsA is 10±2.57 years from the first SpA symptoms appearance. <h3>Conclusions</h3> AH is frequently presented in PsA patients than in AS. Risk of new AH onset in patients with AS and PsA is superior compared with the healthy individuals. The number of new cases of hypertension increases with time, and in 10 years from diagnosis half of PsA/AS patients without cardiovascular disease will be in the risk of hypertension. <h3>References</h3> Agca R et al. Ann Rheum Dis. 2017 Jan;76(1):17–28. <h3>Disclosure of Interest</h3> None declared
Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis
Authors: Noele P. Nelson
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.
Fetal and Infant Growth Patterns and Risk of Lower Lung Function and Asthma. The Generation R Study
Authors: Herman T. den Dekker, Vincent W. V. Jaddoe, Irwin K. Reiss, Johan C. de Jongste, Liesbeth Duijts
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Children with lower birth weight are at increased risk of asthma symptoms.To examine associations of fetal and infant growth with childhood lung function and asthma.This study was embedded in a population-based prospective cohort study of 5,635 children. Growth was estimated by repeated ultrasounds in the second and third trimesters, and measured at birth and at 3, 6, and 12 months. At age 10 years, spirometry was performed and asthma was assessed by parental questionnaire. Restricted and accelerated growth were defined as the growth percentile change between time periods less than -0.67 and more than 0.67 SD scores (SDSs), respectively. We applied multiple regression analyses, including conditional regression analyses, to account for correlations between repeated growth measures.Overall greater weight in the second and third trimesters, at birth, and at 12 months was associated with higher FEV1 and FVC (range of z-score difference, 0.04-0.08, per SDS increase in weight). Greater weight at 3 months was associated with lower FEV1/FVC and forced expiratory flow at 75% of the pulmonary volume (FEF75%) (z-score differences [95% confidence interval]: -0.09 [-0.14 to -0.05] and -0.09 [-0.13 to -0.05] per SDS increase in weight, respectively). Restricted fetal weight growth was associated with lower childhood lung-function measures, partly depending on infant weight growth patterns (range of z-score difference, -0.25 to -0.13). Accelerated fetal weight growth was associated with higher FVC and lower FEV1/FVC only if followed by accelerated infant weight growth. Fetal and infant weight growth was not associated with childhood asthma.Both restricted fetal weight growth, partly depending on infant weight growth, and accelerated fetal and infant weight growth predispose children to lower lung function and a potential risk for respiratory diseases later in life.
Few novel antibiotics in the pipeline, WHO warns
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

The World Health Organization has reiterated its warning that there is a serious lack of new antibiotics under development to combat the growing threat of antimicrobial resistance.

Only eight of the 51 new antibiotics and biologicals in clinical development to treat antibiotic resistant pathogens are innovative treatments that could add value to the current drugs on offer, a new report from the agency has found.1

Most of the drugs in the clinical pipeline are modifications of existing classes of antibiotics and are only short term solutions, …
The Fate of FDA Postapproval Studies
Authors: Steven Woloshin, Lisa M. Schwartz, Brian White, Thomas J. Moore
Journal: New England Journal of Medicine (2017)

The Food and Drug Administration often requires postapproval studies to address issues such as optimal dosing, potential long-term side effects, and use in children or to confirm a drug's clinical benefit. But many of these studies aren't completed on time, if at all.
AB0470 Responsiveness of systemic lupus erythematosus patients after rituximab treatment: a single center experience
Authors: YP Tsao, CY Tsai
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a complex disease with multi-organ presentations. Lupus nephritis, which results from autoantibody deposition at glomerulus, induces inflammation and damage. Lupus nephritis is also the leading cause of comorbidity in SLE patient and associated with poor prognosis. <h3>Objectives</h3> To evaluate the treatment responsiveness of rituximab in patients with SLE. <h3>Methods</h3> Patients should fulfill the criteria of 1997 American College of Rheumatology classification criteria for SLE. Patients underwent chemotherapy, with severe infection, under hemodialysis or after kidney transplantation were excluded. Total 37 patients were evaluated receiving rituximab infusion from 2009 to 2013. Clinical parameters were measured before and after rituximab usage. <h3>Results</h3> Among the 37 patients, the female patient was 89.2%. Mean age was 39.53 years old. The mean creatinine level remained similar during the 36 months of follow-up. In the beginning of the treatment, the mean creatinine level was 1.40mg/dl (SD 0.84). After 12, 24, 36 months of follow-up, the mean creatinine levels were 1.73mg/dl, 2.16mg/dl, and 2.40mg/dl, respectively (p=0.431, 0.148, 0.328). The mean proteinuria level was 3.51g/day initially (SD 2.52), but it rapidly decreased to 1.60g/dl after 6 months of follow-up (p&lt;0.001), and further decreased to 1.40g/day, 1.12g/day, and 0.90g/day after 12, 24, 36 months of follow-up (p=0.001, 0.002, 0.012). The mean ds-DNA level was 216IU/ml in the starting of the treatment, and it decreased to 97.04IU/ml, 88.28IU/ml, 94.6IU/ml after 12, 24, 36 months of follow-up (p=0.002, 0.003, 0.05). The C3 level revealed elevation after 36 months of follow-up. The mean C3 level was 70.63mg/dl initially, and increased to 88.60mg/dl, 90.65mg/dl, and 96.20mg/dl after 12, 24, 36 months of follow-up (p&lt;0.001, 0.002, 0.011). The platelet level remained similar from the beginning of the study to 36 months of follow-up (269.97K/cumm to 253.5K/cumm, p=0.929). The improvement of proteinuria was significant and could be detected in 6 months, which had significant correlations with the reduction level in 24 months (p&lt;0.001). This suggested that early improvement of proteinuria may predict the further responsiveness. <h3>Conclusions</h3> Although the role of rituximab still remained controversial in the treatment of systemic lupus erythematosus, it showed positive effects in our single center9s experience. Early response to rituximab was an important predictor of further sustained responsiveness and reduction of proteinuria and other clinical parameters. <h3>Disclosure of Interest</h3> None declared
AB0511 Vitamin d: potential role in antiphospholipid syndrome
Authors: L Riancho-Zarrabeitia, M Cubería, S García-Canale, G Daroca, M García-Unzueta, JL Hernández, M Lόpez-Hoyos, P Muñoz, M Agudo, V Martínez-Taboada
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Vitamin D, due to its immunoregulatory properties, has been implicated in the pathogenesis of autoimmune diseases, such as antiphospholipid syndrome (APS). <h3>Objectives</h3> A) To determine vitamin D levels in patients with primary APS and to compare them with patients with positive antiphospholipid antibodies (aPL), not meeting clinical criteria for APS, and with healthy controls. B) To analyze the association of the vitamin D levels with both the clinical manifestations and the immunological profile of patients with primary APS. <h3>Methods</h3> We conducted a retrospective study including patients attended at the rheumatology clinic from a tertiary facility in Northern Spain. We included 74 patients with primary APS, 54 patients with positive aPL serology not meeting clinical criteria for APS and 326 healthy controls adjusted by the month of vitamin D analysis. We considered 30 ng/ml and 10 ng/ml as the thresholds for vitamin D insufficiency and deficiency, respectively. <h3>Results</h3> Median levels of vitamin D were similar in the three groups: 21 (range 5–69) in primary APS, 25 (4–50) in the aPL-positive group, and 21 (4–105) in controls. Overall, 53.9% of measurements were performed during the sunny season (April to September). Ten percent of patients with primary APS were males, versus 16% in the aPL serology group and 26% among healthy controls (p=0.007). Mean age was 46±15 in primary APS, 49±17 in the aPL-positive group and 53±10 in the control group (p&lt;0.001). Regarding vitamin D insufficiency, 82% of APS patients had levels of vitamin D (&lt;30 ng/ml) versus 70% and 72% of patients with aPL serology and controls, respectively (p=0.168). When analyzing the prevalence of vitamin D deficiency (&lt;10 ng/ml), we found significant differences across the groups: 16.2% in patients with primary APS, 11.1% in patients with positive serology and only 4.9% in healthy controls (p=0.002). There was no significant association between insufficient levels of vitamin D and the presence of thrombotic or obstetric events. Nevertheless, we found a trend for the presence of more thrombotic events in patients with vitamin D deficiency (p=0.097). Regarding the immunological profile, we found no association between vitamin D and either the number of positive antibodies or their serological evolution. However, we found an association between insufficient levels of vitamin D and the presence of lupus anticoagulant (54.7% vs 18.2%, p=0.047) <h3>Conclusions</h3> More than 80% of patients with primary APS have insufficient levels of vitamin D and 16% of them have very low levels of vitamin D. Primary APS patients show a higher frequency of vitamin D deficiency than healthy controls. Patients with vitamin D insufficiency have more commonly positivity for lupus anticoagulant. <h3>Disclosure of Interest</h3> None declared
Research Gaps and Controversies in Chronic Traumatic Encephalopathy
Authors: Breton M. Asken, Molly J. Sullan, Steven T. DeKosky, Michael S. Jaffee, Russell M. Bauer
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic encephalopathy (CTE). Chronic traumatic encephalopathy is a tauopathy associated with RBT that has become inextricably linked to conversations about sport-related concussion and mild traumatic brain injury. Accordingly, specific populations such as collision sport athletes and certain military personnel are of particular interest owing to their unique exposure to RBT. The gaps and controversies in our understanding of the epidemiologic factors, mechanism, and clinicopathological correlates of CTE reflect the current reliance on postmortem case series investigations. This review discusses the state of the science of CTE and raises considerations for researching and interpreting cognitive changes in members of at-risk populations. <h3>Observations</h3> The recent development of pathological diagnostic criteria for CTE represented an important step for differentiating CTE from other neurodegenerative diseases. By comparison, defining the clinical syndrome(s) associated with CTE and the necessary and sufficient symptoms needed for its diagnosis lags behind. The absence of validated in vivo biomarkers of pathological characteristics of CTE and longitudinal tracking with neuropsychological evaluation remains a significant hurdle. Attribution of candidate symptoms in retired athletes to CTE is complicated by the presence of multiple premorbid and comorbid factors affecting cognitive reserve that influence normal or expected cognitive functioning. This is a critical issue in appropriately defining reference groups for normative comparisons. <h3>Conclusions and Relevance</h3> Available data, while limited and complicated by selection bias, indicate that exposure to RBT represents the greatest risk factor for CTE pathological features, although clinicopathological correlates and the nature of onset and progression of symptoms are largely unknown. Considering aspects of cognitive reserve is likely essential for both interpreting cognitive outcomes associated with CTE and for developing preventive treatment programs. Research on CTE would benefit greatly from incorporating principles established within other areas of neurodegenerative disease and the nuances of clinicopathological considerations.
Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events
Authors: Peter H. Stone, Akiko Maehara, Ahmet Umit Coskun, Charles C. Maynard, Marina Zaromytidou, Gerasimos Siasos, Ioannis Andreou, Dimitris Fotiadis, Kostas Stefanou, Michail Papafaklis, Lampros Michalis, Alexandra J. Lansky, Gary S. Mintz, Patrick W. Serruys, Charles L. Feldman, Gregg W. Stone
Journal: JACC. Cardiovascular imaging (2017)
AB0003 A mif promoter polymorphism is associated with the susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis patients
Authors: E Lόpez-Isac, L Bossini-Castillo, D Campillo-Davό, FD Carmona, CP Simeόn, P Carreira, JL Callejas-Rubio, I Castellví, A Fernández-Nebro, L Rodríguez-Rodríguez, M Rubio Rivas, FJ Hernández García, AB Madroñero, S Scleroderma Group, L Beretta, A Santaniello, C Lunardi, P Airό, A-M Hoffmann-Vold, A Kreuter, G Riemekasten, T Witte, N Hunzelmann, MC Vonk, AE Voskuyl, JDV Bouwstra, P Shiels, A Herrick, J Worthington, TRDJ Radstake, J Martin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in SSc patients. However, the genetic factors involved in lung complication are not well-defined. <h3>Objectives</h3> We aimed to revisit the association of the MIF gene, which encodes a cytokine implicated in idiopathic pulmonary hypertension among other diseases, with the susceptibility and clinical expression of SSc, besides testing the association of this polymorphism with SScrelated pulmonary involvement. <h3>Methods</h3> A total of 4,393SSc patients and 16,591 unaffected controls from six cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to meta-analyze the data. <h3>Results</h3> A statistically significant increase of the MIF rs755622*C allele frequency compared to controls was observed in the subgroups of patients with diffuse cutaneous SSc (dcSSc) and with pulmonary arterial hypertension (PAH) independently (dcSSc: P=3.20E-2, OR=1.13; PAH: P=2.19E-02, OR=1.32). However, our data revealed a stronger effect size with the subset of SSc patients showing both clinical manifestations (dcSSc with PAH: P=6.91E-3, OR=2.05). <h3>Conclusions</h3> We revisited the association of the MIF rs755622*C allele with SSc and described a phenotype-specific association of this variant with the susceptibility to develop PAH in dSSc patients. <h3>Disclosure of Interest</h3> None declared
SP0121 Long term side effects of biological agents in jia
Authors: JF Swart
Journal: Annals of the Rheumatic Diseases (2017)

In the last years, the interest in the concept of comorbidity and its societal as well as individual impact has increased. Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease starting in childhood which often persists into adulthood. Clinicians are facing an aging population with multiple morbid conditions occurring in one individual. Long term outcome studies show the high prevalence and the potential interaction of coexisting diseases. For JIA recent studies reported that uveitis, asthma/atopic diseases and diabetes mellitus are prevalent comorbidities in JIA with 11.6–30%, 10.8% and 3.5% respectively, followed by cardiovascular disease, malignancies and inflammatory bowel diseases. Childhood long term outcome studies and Pharmacovigilance registries already revealed associations of co-existing diseases and the role of used medication (especially biologicals). It is important to plan preventive and screening strategies in order to prevent or early detect and treat comorbidities and integrated follow up once comorbidity exists. <h3>Disclosure of Interest</h3> None declared
THU0340 Adrenal insufficiency during glucocorticoid treatment in patients with polymyalgia reumatica or giant cell arteritis
Authors: T Laursen, H Locht, B Jensen, S Borresen, U Feldt-Rasmussen, L Hilsted, EM Bartels
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adrenal insufficiency secondary to long-term systemic glucocorticoid treatment is a well-recognized problem. However, the extent and prevalence of this phenomenon has not been thoroughly explored. <h3>Objectives</h3> To investigate the prevalence of adrenal insufficiency in patients with polymyalgia reumatica (PMR) and giant cell arteritis (GCA) during treatment with low doses of prednisolone (&lt;10mg/day) assessed by the adrenal response to a 250 microgram Synachten® test. To explore whether potential adrenal insuffiency was associated with duration of steroid treatment. <h3>Methods</h3> Outpatients were examined when prednisolone doses were between 2.5 and 10 mg/day for &gt;6 months. Adrenal function was evaluated after a 48-hour pause of prednisolone, using a 250 μg Synachten® (ACTH) test where plasma cortisol levels were measured at baseline and 30 minutes after Synacthen injection. Adrenal insufficiency was defined as plasma cortisol &lt;420 nmol/l after 30 minutes according to the validated Roche Elecsys®Cortisol II assay. Accummulated doses of prednisolone for the individual patients were calculated. A multiple regression analysis was used to test for an association between the plasma cortisol after 30 minutes and the accumulated dose of prednisolone. <h3>Results</h3> Forty-eight patients (35 women) completed the Synachten® test. Seven (14.6%) patients exhibited adrenal insufficiency. Median age was 74 years (Range: 57–89 years). Median accumulated dose was 3.402 mg (Range: 820–21.200mg). Median plasma cortisol after 30 minutes was 562 nmol/l (Range: 92–989 nmol/l). In patients with adrenal insufficiency, median plasma cortisol was 122 nmol/l (Range: 56–275 nmol/l) at baseline and 207 (Range: 92–420 nmol/l) after 30 minutes. In patients without adrenal insufficiency, median plasma cortisol was 359 (Range: 9–710 nmol/l) at baseline and 584 nmol/l (Range: 429–989 nmol/l) after 30 minutes. Accumulated doses of prednisolone did not differ in patients with and without adrenal insufficiency (p=0.49). Plasma cortisol after 30 minutes was not associated with accumulated dose of prednisolone (estimate −0.01, 95% CI: −0.02 to 5.39, p=0.06), when adjusting for sex and age. <h3>Conclusions</h3> Iatrogenic adrenal insufficiency was prevalent among patients with PMR or GCA treated with low dose prednisolone. Adrenal function was not associated with the accumulated dose of prednisolone, or the duration of steroid treatment. A Synacthen® test is a valuable tool to evaluate the adrenal function, when steroid treatment is tapered in these patients. Latent symptoms of adrenal insufficiency may explain why some patients are reluctant to discontinue steroid treatment even after the inflammatory condition has gone into remission. <h3>Disclosure of Interest</h3> None declared