Rheumatology

Current Awareness Newsletter

December 2015

Outreach Your Outreach Librarian can help facilitate evidence-based practise for all Rheumatology staff, as well as assisting with academic study and research. We can help with literature searching, obtaining journal articles and books, and

setting up individual current awareness alerts.

Literature Searching We provide a literature searching service for any library member. For those embarking on their own research it is advisable to book some time with one of the librarians for a 1 to 1 session where we

can guide you through the process of creating a well-focused literature research and introduce you to the health databases

access via NHS Evidence.

Critical Appraisal Training We also offer one-to-one or small group training in

literature searching, accessing electronic journals, and critical appraisal/Statistics. These are essential courses that teach how to

interpret clinical papers.

For more information, email: katie.barnard@uhbristol.nhs.uk

Books Books can be searched for using SWIMS our online catalogue at

www.swims.nhs.uk. Books and journals that are not available on site or electronically may be requested from other locations.

Please email requests to: library@uhbristol.nhs.uk

Contents

1: Tables of Contents from

December’s Rheumatology

journals

2: New NICE Guidance

3: Latest relevant Systematic

Reviews from the Cochrane

Library.

4: New activity in Uptodate

5: NHS Behind the Headlines

6: Quick exercise

7: Current Awareness database

articles

Tables of Contents from Rheumatology journals

The links below will take you to the full Tables of Contents.

If you require full articles please email: library@uhbristol.nhs.uk

Rheumatology December 2015 Volume 54 Issue 12

Annals of Rheumatic Disease December 2015 Volume 74 Issue 12

Arthritis & Rheumatology December 2015 Volume 67 Issue 12

Journal of Rheumatology December 2015 Volume 42 Issue 12

Osteoporosis International December 2015 Volume 26 Issue 12

New NICE Guidance

NG24 Blood transfusion

Latest relevant Systematic Reviews

from the Cochrane Library

Decision aids for people considering taking part in clinical trials

New activity in Uptodate

www.uptodate.com

You will need your NHS Athens username/password (register through http://openathens.nice.org.uk/)

Secukinumab, an anti-IL17A antibody, for psoriatic arthritis (August 2015, Modified November

2015)

Secukinumab, an anti-interleukin (IL)-17A antibody, is available for the treatment of psoriasis in the

United States and other countries and has been evaluated for psoriatic arthritis (PsA) using various

routes of administration and dosing regimens. In a multicenter randomized trial of almost 400 patients

with active PsA, subcutaneously injected secukinumab was superior to placebo in achieving

significant improvement in joint and skin disease, and in physical function and quality of life at week

24, with sustained benefit at one year [13]. A subsequent trial of over 600 patients demonstrated that

secukinumab, loaded intravenously and then given subcutaneously, resulted in similar clinical

outcomes and also reduced radiographic progression of PsA [14]. (See "Treatment of psoriatic

arthritis", section on 'IL-17 blockade'.)

NHS Behind the Headlines

Stronger legs linked to stronger brains in older women

Wednesday Nov 11 2015

"Strong legs 'help the brain resist the effects of ageing','' the Mail Online reports. A study that

tracked 324 female twins (162 sets) over 10 years found an association between leg strength

and cognitive ability, measured…

Quick exercise

Systematic Reviews There are 7 key steps that need to be taken when carrying out a Systematic Review. Can you put them in order?

A. Quality assessment

B. Study selection

C. Synthesis

D. Data extraction

E. Define the question

F. Literature search

G. Writing up

For assistance with carrying out a systematic review search or a literature search, please email library@uhbristol.nhs.uk.

Current Awareness database articles

If you require full articles please email: library@uhbristol.nhs.uk

Title: Quinones as novel chemiluminescent probes for the sensitive and selective determination of biothiols in biological fluids. Citation: The Analyst, Nov 2015, vol. 140, no. 24, p. 8148-8156 (November 23, 2015) Author(s): Elgawish, Mohamed Saleh, Kishikawa, Naoya, Kuroda, Naotaka Abstract: Altered plasma aminothiol concentrations are thought to be a valuable risk indicator and are interestingly utilized for routine clinical diagnosis and for the monitoring of various metabolic disorders and human diseases, and accordingly there is a need for an accurate and reliable assay capable of simultaneously determining aminothiols including glutathione (GSH), N-acetylcysteine (NAC), homocysteine (Hcys), and cysteine (Cys) in human plasma. Herein, a highly sensitive, selective, and very fast HPLC-chemiluminescence (HPLC-CL) coupled method is reported, exploiting for the first time the strong nucleophilicity and high reactivity of aminothiols toward quinones for a CL assay. The unique redox-cycling capability of quinone and/or Michael addition adducts, thioether-quinone conjugates, was utilized to establish a novel analytical method based on the reaction of adducts with dithiothreitol (DTT) to liberate reactive oxygen species (ROS), which are detected by using a luminol-CL assay. Specimen preparation involved the derivatization of aminothiols with menadione (MQ) for 5 minutes at room temperature. A unique green chemistry synthesis of thioether-quinones in HEPES buffer (pH 8.5) was introduced by using our reaction methodology without needing any hazardous organic solvent or catalyst. The aminothiol-MQ adducts were separated using solid-phase extraction followed by isocratic elution on an ODS column. Linearity was observed in the range of 2.5-500, 5-500, 10-1500, and 20-2000 nM with detection limits (S/N of 3) of 3.8, 4.2, 8, and 16 (fmol per injection) for GSH, NAC, Hcys, and Cys, respectively. The method was successfully applied for the selective determination of aminothiols in human plasma from healthy people and patients with rheumatic arthritis and diabetes mellitus. The obtained results postulated the usefulness of our method for investigating the relationship between aminothiol metabolism and related human disorders. Full Text:

Available from Royal Society of Chemistry NHS Pilot 2014 (NESLi2) in Analyst; Note: ; Collection notes: Only available on NHS networked computers. Not available with Athens username/password.

Title: Efficacy of Rituximab for Pemphigus: A Systematic Review and Meta-analysis of Different Regimens. Citation: Acta dermato-venereologica, Nov 2015, vol. 95, no. 8, p. 928-932 (November 4, 2015) Author(s): Wang, Hsiao-Han, Liu, Che-Wei, Li, Yu-Chuan, Huang, Yu-Chen Abstract: This meta-analysis examined the efficacy of different dosing regimens containing rituximab (RTX) in treating pemphigus. The analysis included 578 patients with pemphigus from 30 studies. Seventy-six percent of patients achieved complete remission (CR) after 1 cycle of RTX. Mean time to remission was 5.8 months, with a remission duration of 14.5 months and a 40% relapse rate. Eighteen patients (3.3%) developed serious adverse effects. The pooled estimate showed no significant differences in CR and relapse rates between patients treated with high-dose (near or ≥ 2,000 mg/cycle) vs. low-dose (< 1,500 mg/cycle) RTX. In the fully adjusted analysis, high-dose RTX was associated with longer duration of CR compared with low-dose RTX. No superiority of lymphoma protocol over rheumatoid arthritis or high-dose RTX over low-dose RTX was shown in other outcomes. RTX treatment is efficacious and well-tolerated in treating pemphigus. High-dose RTX treatment may lead to longer duration of remission. However, the choice of optimal regimen depends on the overall condition of the individual patient.

Title: Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients. Citation: Circulation, Nov 2015, vol. 132, no. 18, p. 1693-1700 (November 3, 2015) Author(s): Mekinian, Arsene, Comarmond, Cloé, Resche-Rigon, Mathieu, Mirault, Tristan, Kahn, Jean Emmanuel, Lambert, Marc, Sibilia, Jean, Néel, Antoine, Cohen, Pascal, Hie, Miguel, Berthier, Sabine, Marie, Isabelle, Lavigne, Christian, Anne Vandenhende, Marie, Muller, Géraldine, Amoura, Zahir, Devilliers, Hervé, Abad, Sébastien, Hamidou, Mohamed, Guillevin, Loïc, Dhote, Robin, Godeau, Bertrand, Messas, Emmanuel, Cacoub, Patrice, Fain, Olivier, Saadoun, David, French Takayasu Network Abstract: The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis. This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20-55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1-5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10-46 mg/L] versus 58 mg/L [26-76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%-99%) over the biological treatment period compared with 58.7% (43.3%-79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2-95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile. © 2015 American Heart Association, Inc. Full Text:

Available from Ovid in Circulation

Available from Highwire Press in Circulation

Title: EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice. Citation: Annals of the rheumatic diseases, Nov 2015, vol. 74, no. 11, p. 1946-1957 (November 2015) Author(s): Colebatch-Bourn, A N, Edwards, C J, Collado, P, D'Agostino, M-A, Hemke, R, Jousse-Joulin, S, Maas, M, Martini, A, Naredo, E, Østergaard, M, Rooney, M, Tzaribachev, N, van Rossum, M A, Vojinovic, J, Conaghan, P G, Malattia, C Abstract: To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were

included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. Full Text:

Available from Highwire Press in Annals of the Rheumatic Diseases

Title: Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-Analysis of Randomized Trials. Citation: Arthritis care & research, Nov 2015, vol. 67, no. 11, p. 1487-1495 (November 2015) Author(s): Graudal, Niels, Hubeck-Graudal, Thorbjørn, Faurschou, Mikkel, Baslund, Bo, Jürgens, Gesche Abstract: The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (-0.09 units [-0.61, 0.44]) of treatment or during the first 2 years (0.66 units [-0.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors. © 2015, American College of Rheumatology.

Title: Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry. Citation: Arthritis care & research, Nov 2015, vol. 67, no. 11, p. 1529-1535 (November 2015) Author(s): Foeldvari, Ivan, Becker, Ingrid, Horneff, Gerd Abstract: Uveitis is a major extraarticular quality of life-restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX). Patients' characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated. Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001),

and more often received adalimumab (OR 2.15 [95% confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR 1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8 years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis. Patients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept. © 2015, American College of Rheumatology.

Title: Symptoms of Depression and Risk of New Episodes of Low Back Pain: A Systematic Review and Meta-Analysis. Citation: Arthritis care & research, Nov 2015, vol. 67, no. 11, p. 1591-1603 (November 2015) Author(s): Pinheiro, Marina B, Ferreira, Manuela L, Refshauge, Kathryn, Ordoñana, Juan R, Machado, Gustavo C, Prado, Lucas R, Maher, Christopher G, Ferreira, Paulo H Abstract: To investigate the contribution of symptoms of depression to future episodes of low back pain (LBP). A search was conducted of AMED, CINAHL, Embase, Health and Society (H&S), LILACS, MEDLINE, PsycINFO, Scopus, and Web of Science databases. We included cohort studies investigating the effect of symptoms of depression on the development of new episodes of LBP, either lifetime incidence or a recurrent episode, in a population free of LBP at baseline. We accepted the original study's definition for a new episode of LBP, and for classifying patients as LBP-free at study entry. Two independent investigators extracted data and assessed methodological quality. Meta-analyses with random effects were used to pool risk estimates. We included 19 studies, with 11 incorporated in the meta-analyses. Overall pooled results showed that symptoms of depression increased the risk of developing LBP (odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.26-2.01). The risk was similar in studies that used the diagnostic interview method (OR 1.66, 95% CI 1.14-2.42) and in studies using self-report screening questionnaires (OR 1.68, 95% CI 1.05-2.70). No statistically significant relationship was observed when we pooled studies that employed nonspecific screening questionnaires (OR 1.17, 95% CI 0.48-2.87). Three studies provided results in incremental categories of symptoms of depression and the pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58-3.99) was higher than for the lowest level (OR 1.51, 95% CI 0.89-2.56). Individuals with symptoms of depression have an increased risk of developing an episode of LBP in the future, with the risk being higher in patients with more severe levels of depression. © 2015, American College of Rheumatology.

Title: Potential Application of Biological Products for the Treatment of Ocular Surface Inflammation. Citation: Cornea, Nov 2015, vol. 34 Suppl 11, p. S153. (November 2015) Author(s): Sakimoto, Tohru Abstract: Various biological products have been introduced for the treatment of autoimmune diseases. The injection of tocilizumab [anti-interleukin (IL)-6R antibody] and a tumor necrosis factor receptor fusion protein (TNFR-Fc) has been approved for the treatment of rheumatoid arthritis. We investigated the effect of the anti-IL-6R antibody and TNFR-Fc on corneal inflammation. Topical instillation of the anti-IL-6R antibody (MR16-1, 2 μg/μL; anti-IL-6R group) or TNFR1-Fc (100 μg/mL; TNFR1 group) was performed after corneal wounds were induced in BALB/c mice by alkali burns. The injured eye was analyzed on day 14 or 28 after injury, and topical instillation was performed until day 14 or day 28. Corneal stromal sections were made using a laser capture microdissection system, and total RNA from the specimens was subjected to quantitative polymerase chain reaction array analysis. Topical instillation of phosphate-buffered saline (PBS) served as a control. The vascularized area was significantly reduced in the anti-IL-6R (day 14) and TNFR1 groups (day 28) compared

with that in the PBS group. In the anti-IL-6R group, the expression levels of matrix metalloproteinase-13, monocyte chemotactic protein-1, and C-C motif ligand-22 were downregulated compared with those in the PBS group. In the TNFR1 group, expression of mitogen-activated protein kinase 8 was downregulated. These results indicate the possible application of biological products for topical instillation for the treatment of corneal inflammation.

Title: Immunotherapeutic Biologic Agents in Autoimmune and Autoinflammatory Diseases. Citation: Immunological investigations, Nov 2015, vol. 44, no. 8, p. 777-802 (November 2015) Author(s): Ostrov, Barbara E Abstract: In recent decades, innovative strategies to treat patients with inflammatory, immunologically based diseases have advanced in concert with our increased understanding of molecular immunology. Recognition of the spectrum and pathophysiology of autoimmune and autoinflammatory disorders has allowed for the development of cutting-edge therapies for such patients. In this review, key immunotherapeutic approaches for treating inflammatory autoimmune disorders, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as genetic autoinflammatory diseases, such as cryopyrin associated periodic syndromes, are addressed. Indications, risks and additional considerations in the use of these agents are reviewed.

Title: Treatment of hidradenitis suppurativa with biologic medications. Citation: Journal of the American Academy of Dermatology, Nov 2015, vol. 73, no. 5 Suppl 1, p. S82. (November 2015) Author(s): Lee, Robert A, Eisen, Daniel B Abstract: Given the absence of significant improvement in the treatment of hidradenitis suppurativa (HS) with traditional medical and surgical therapies, biologics have piqued the interest of research investigators. The efficacy of biologics in the treatment of inflammatory conditions like psoriasis and rheumatoid arthritis is well-documented. More recently, success with biologics has been demonstrated in atopic dermatitis, another dermatological condition associated with inflammatory states. Researchers have begun to probe the utility of biologic agents in less prevalent conditions that feature inflammation as a key characteristic, namely, hidradenitis suppurativa. Five agents in particular adalimumab, anakinra, etanercept, infliximab, and ustekinumab, have been explored in the setting of HS. Results to date put forward adalimumab and infliximab as biologic treatments that can safely be initiated with some expectant efficacy. Other biologic agents require more rigorous examination before they are worthy of addition to the treatment armamentarium. Copyright © 2015. Published by Elsevier Inc.

Title: Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance imaging in biologic agent-naïve early-stage rheumatoid arthritis patients. Citation: Modern rheumatology / the Japan Rheumatism Association, Nov 2015, vol. 25, no. 6, p. 948-953 (November 2015) Author(s): Kawashiri, Shin-Ya, Suzuki, Takahisa, Nakashima, Yoshikazu, Horai, Yoshiro, Okada, Akitomo, Iwamoto, Naoki, Ichinose, Kunihiro, Tamai, Mami, Arima, Kazuhiko, Nakamura, Hideki, Origuchi, Tomoki, Uetani, Masataka, Aoyagi, Kiyoshi, Kawakami, Atsushi Abstract: Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in

2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI.

Title: Management of Psoriatic Arthritis: Traditional Disease-Modifying Rheumatic Agents and Targeted Small Molecules. Citation: Rheumatic diseases clinics of North America, Nov 2015, vol. 41, no. 4, p. 711-722 (November 2015) Author(s): Soriano, Enrique R Abstract: Traditional disease-modifying antirheumatic drugs (DMARD) remain the first-line treatment of psoriatic arthritis (PsA), despite lack of randomized controlled trials, and with evidence based on observational studies. Anti-tumor necrosis factor agents remain a top choice for biologic treatment, complemented with new biologics with different targets (IL12-23 and IL17). Unmet needs have been identified for patients who do not respond to treatment. Among targeted small molecules Apremilast is approved for the treatment of PsA and Tofactitinib is under investigation. The drugs discussed herein have the potential to address unmet needs; however, additional research is required to identify more effective therapies for PsA. Copyright © 2015 Elsevier Inc. All rights reserved.

Title: A systematic review of non-pharmacological interventions for primary Sjögren's syndrome. Citation: Rheumatology (Oxford, England), Nov 2015, vol. 54, no. 11, p. 2025-2032 (November 2015) Author(s): Hackett, Katie L, Deane, Katherine H O, Strassheim, Victoria, Deary, Vincent, Rapley, Tim, Newton, Julia L, Ng, Wan-Fai Abstract: To evaluate the effects of non-pharmacological interventions for primary SS (pSS) on outcomes falling within the World Health Organization International Classification of Functioning Disability and Health domains. We searched the following databases from inception to September 2014: Cochrane Database of Systematic Reviews; Medline; Embase; PsychINFO; CINAHL; and clinical trials registers. We included randomized controlled trials of any non-pharmacological intervention. Two authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data. A total of 1463 studies were identified, from which 17 full text articles were screened and 5 studies were included in the review; a total of 130 participants were randomized. The included studies investigated the effectiveness of an oral lubricating device for dry mouth, acupuncture for dry mouth, lacrimal punctum plugs for dry eyes and psychodynamic group therapy for coping with symptoms. Overall, the studies were of low quality and at high risk of bias. Although one study showed punctum plugs to improve dry eyes, the sample size was relatively small. Further high-quality studies to evaluate non-pharmacological interventions for PSS are needed. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Title: Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Citation: Rheumatology (Oxford, England), Nov 2015, vol. 54, no. 11, p. 2042-2050 (November 2015) Author(s): Rodríguez-García, Veronica, Ioannou, Yiannis, Fernández-Nebro, Antonio, Isenberg, David A, Giles, Ian P Abstract: To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations. We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-

Domain I, IgA anti-β2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined. We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%). Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Title: Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review. Citation: The Journal of rheumatology, Nov 2015, vol. 42, no. 11, p. 2012-2022, 0315-162X (November 2015) Author(s): Kuijper, T Martijn, Lamers-Karnebeek, Femke B G, Jacobs, Johannes W G, Hazes, Johanna M W, Luime, Jolanda J Abstract: To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy. A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers. Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17-0.39) and 0.49 (95% CI 0.27-0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression. Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.

Title: Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group. Citation: The Journal of rheumatology, Nov 2015, vol. 42, no. 11, p. 2168-2171, 0315-162X (November 2015) Author(s): Khanna, Dinesh, Mittoo, Shikha, Aggarwal, Rohit, Proudman, Susanna M, Dalbeth, Nicola, Matteson, Eric L, Brown, Kevin, Flaherty, Kevin, Wells, Athol U, Seibold, James R, Strand, Vibeke Abstract: Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in

RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO. There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.

Title: Enhanced Patient Involvement and the Need to Revise the Core Set - Report from the Psoriatic Arthritis Working Group at OMERACT 2014. Citation: The Journal of rheumatology, Nov 2015, vol. 42, no. 11, p. 2198-2203, 0315-162X (November 2015) Author(s): Tillett, William, Eder, Lihi, Goel, Niti, De Wit, Maarten, Gladman, Dafna D, FitzGerald, Oliver, Campbell, Willemina, Helliwell, Philip S, Gossec, Laure, Orbai, Ana-Maria, Ogdie, Alexis, Strand, Vibeke, McHugh, Neil J, Mease, Philip J Abstract: To discuss the need for revision of the "core set" of domains to be included for assessment in psoriatic arthritis (PsA) randomized controlled trials and longitudinal observational studies, review work undertaken since the 2012 meeting of Outcome Measures for Rheumatology 11 (OMERACT 11) to include patient perspectives in this revision, and reassess proposed composite measures in the context of new research data and the OMERACT Filter 2.0 framework. The OMERACT 12 (2014) PsA working group presented work completed over the last 2 years to incorporate patient involvement in PsA outcomes research, review the endorsed PsA core set based on the patient perspective as well as new research findings, and further develop PsA responder indices. Breakout groups then discussed 2 topics: (1) the need to revise the PsA core set, and opportunities to add, move, or merge existing domains to improve existing redundancy; and (2) how to incorporate the core set in a composite index. Breakout groups fed back to the working group before participant voting. Meeting participants endorsed the need to revise the PsA core set according to the OMERACT Filter 2.0 framework (100%), and the inclusion of disease impact (94%) and fatigue (72%) in the inner circle. Breakout group feedback suggested the core set revision was an opportunity to consolidate pathophysiologic aspects such as arthritis, enthesitis, dactylitis, spondylitis as "inflammatory musculoskeletal disease," and nail and skin psoriasis as "psoriasis activity." Future work will focus on updating the PsA core set and development of responder indices with ongoing, meaningful involvement of patient research partners.

Title: Network Meta-Analysis of Biological Response Modifiers in Rheumatoid arthritis Including real World Evidence at Multiple time Points. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A343. (November 2015) Author(s): Jenkins, D, Martina, R, Bujkiewicz, S, Dequen, P, Abrams, K

Title: Reduction In C-Reactive Protein With Biologic Drugs In Rheumatoid Arthritis and Spondylitis Patients In German Rheumatologist Practices. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A635. (November 2015) Author(s): Gossen, N, Kostev, K

Title: A Network Metanalysis Comparing The Efficacy of Biologics for The Treatment of Early Rheumatoid Arthritis.

Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A636. (November 2015) Author(s): Bizzi, E, Petrella, L, Integlia, D, Migliore, A

Title: Identification of Osteoporosis & Chronic Inflammatory Rheumatic Disease In French Claims Data. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A637. (November 2015) Author(s): Belhassen, M, Levy-Bachelot, L, Laforest, L, Ginoux, M, van Ganse, E

Title: Pharmacoeconomic Analysis of Different Strategies of Monotherapy With Biologic Therapies In Russian Patients With Rheumatoid Arthritis. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A645. (November 2015) Author(s): Ryazhenov, V V, Gorokhova, S G

Title: Biological Agents for Patients With Rheumatoid Arthritis Who Had Failed Treatment With Methotrexate In The Spanish Clinical Setting: A Cost-Effectiveness Analysis. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A645. (November 2015) Author(s): Sánchez, R, Restovic, G, Planellas, L

Title: Controlling the Cost Spent on Expensive Biologic Agents: an Example of Net Monetary Savings By Dose Optimisation of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis Patients. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A647. (November 2015) Author(s): Kievit, W, van Herwaarden, N, van den Hoogen, F, van Vollenhoven, R, Bijlsma, H, van den Bemt, B, van der Maas, A, den Broeder, A

Title: Cost-Effectiveness of Biologics Compared to Conventional Disease-Modifying Antirheumatic Drugs for Treatment of Rheumatoid Arthritis in Finland. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A648. (November 2015) Author(s): Joensuu, J T, Aaltonen, K J, Aronen, P, Sokka, T, Puolakka, K, Tuompo, R, Korpela, M, Vasala, M, Ilva, K, Nordström, D, Blom, M

Title: Patients' Preferences for Rheumatoid Arthritis Treatments and their Participation in the Treatment Decision-Making Process. A Systematic Review of the Literature. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A652. (November 2015)

Author(s): Dilla, T, Rentero, M L, Comellas, M, Lizan, L, Sacristán, J A

Title: Characteristics of Patients Starting Biologic Treatments for Rheumatoid Arthritis in The Real World: Systematic Review. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A657. (November 2015) Author(s): Kilcher, G, Didden, E, Hummel, N, Egger, M

Title: Review of Economic Models for The Evaluation of Biologic Dmards In Rheumatoid Arthritis. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A696. (November 2015) Author(s): Van Laer, J, Gubbels, L, Rodriguez, I L, Maervoet, J, Nijhuis, T, Nielsen, A T, Peterson, S, Hemels, M, Ganguly, R

Title: Cost Reduction For A Health System Through Decreasing Number Of Eligible Patients For Biological Therapy In Patients With Rheumatoid Arthritis Using The Treat To Target Recommendations. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A808. (November 2015) Author(s): Santos-Moreno, P, Saavedra-Martínez, G, Bello-Gualtero, J, Gómez-Mora, D

Title: Occurrence of Treatment Interruption During Therapy with Biological Agents in Patients with Previous Anti-Tnf Failure in Rheumatoid Arthritis. Citation: Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Nov 2015, vol. 18, no. 7, p. A874. (November 2015) Author(s): Piazza, T, Tonin, F S, Steimbach, L M, Wiens, A, Pontarolo, R

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