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Clinicians, health service planners and public health policy-makers all understand the value of data which describe the occurrence of disease in the community. Routinely collected mortality statistics, for example, have made an enormous contribution to understanding the causes of disease, measuring the impact of prevention and health-care, and the planning of health services. However, a modern rheumatological readership will understand the point made forcibly in the 1980 Black Report on Inequalities in Health, that ‘undue dependence on mortality rates can induce comparative indifference towards problems of chronic illness’, since such indifference is still evident in health policy and research priorities today. The report emphasized the need for statistics on morbidity, especially chronic disease. The problem with morbidity is that, unlike death, much of the everyday experience of illness is not routinely recorded, whilst periodic surveys of the health of the general population, such as those carried out by the Office of National Statistics, whilst important, only provide a snapshot of the occurrence of selected problems at certain times. One source of routine and continuing data on morbidity in the UK is general practice. More than 95% of people are registered with a general practice and the patient records held by those practices provide a picture of morbidity from cradle to grave. Furthermore, general practice is the first point of access to the National Health Service for most non-emergency care in the UK. Although many people with musculoskeletal symptoms seek advice and care from other sources, such as friends and neighbours, pharmacists, complementary therapists or private practitioners, most also use general practice. Most general practices in Britain are now recording at least some data electronically. This means that information on events arising from consultations in this setting—such as diagnosis, drugs prescribed, tests and referrals, as well as lifestyle data such as smoking status and body mass index—are becoming more readily available. Whilst this brings benefits for the organization and monitoring of clinical practice, such consultation data also provide an important source of information on the occurrence of symptoms and disease, and their treatment and care, and an important resource for researchers. The growing importance of general practice databases is evidenced by the number of research articles generated from one of the largest samples of archived consultations in the UK, the General Practice Research Database (GPRD). Since 1990, 450 papers have been published using the GPRD. However, most have been about pharmacological issues, and the number of musculoskeletal research papers using GPRD or other similar databases is small. Researchers in rheumatology are, however, beginning to exploit the information which can be yielded by such consultation archives. The paper by Linsell and colleagues on a prospective study of patients consulting with shoulder problems using the Mediplus database [1] and a study by the same authors on patients with hip and knee problems [2] are examples of this. GPRD and Mediplus are just two of an increasing number of large anonymized UK sets of routinely collected consultation data potentially available to researchers. For example, the GPRD contains data from around 300 practices across the country, covering an equivalent of 5% of the UK population. Others include the Weekly Returns Service run by the Royal College of General Practitioner's Birmingham Research Unit [3], QRESEARCH [4] and the Doctor's Independent Network (DIN) [5]. There are also regionally organized databases, such as our local North Staffordshire Consultations in Primary Care Archive (CiPCA), which contains validated data from 10 local practices [6]. General practice data routinely recorded about every contact offer the attractive possibility of charting the full range of musculoskeletal morbidity and how it is managed over time. There are caveats to this optimism, however, and as these databases become more widely available the positive reasons to use them must be considered in the context of potential constraints on their quality and interpretation. The strengths and weaknesses of specific databases have been discussed previously [7], but researchers need to be aware of aspects of general practice consultation recording that may be considered as limiting its value for research. The first and most obvious point is that many general practices may not yet be recording all patient contacts on their computerized systems or systematically coding the reasons for those contacts. Various methods have been used to assess the quality of morbidity recording in general practice [8]. For example, Hassey et al. cross-referenced diagnostic codes with relevant drug prescriptions and a recorded seropositive rheumatoid factor to check on the completeness of records of rheumatoid arthritis in one practice [9]. The quality of prescription recording has tended to be better than that for recording morbidity [10]. However, the situation is improving as general practitioners (GPs) become more familiar with electronic recording. Computerized morbidity data are now being used by the government to assess the quality of care being provided and to renumerate practices on that basis. This should encourage both the completeness of computerized recording of patient contacts and the accuracy of coding. One of the claims of some of the large systematically organized databases is that they only use data from practices signed up to training and rules about regular recording of contacts. However, each database follows rather different rules which may not necessarily reflect what the average GP does. In the GPRD, for example, GPs only have to code morbidities on the first occasion and when a treatment is first issued. Whilst the GPRD appears an excellent resource for pharmacology research, these instructions mean that its use in exploring patterns of consultation may be more limited than that of other databases. The second issue—and one that creates more doubts for the specialist rheumatologist than the first—is that there are no standardized methods of applying diagnostic labels in general practice. GPs are faced with an array of alternative codes for the same or similar conditions. One of the advantages of the coding systems used in practice is that the label applied can be a presenting symptom (‘shoulder pain’), but a disadvantage is that the basis for applying a diagnostic label, such as subacromial bursitis, may vary from GP to GP. The decision to use a label of joint pain rather than osteoarthritis may be down to habit or to whether the GP has decided to refer the patient for X-ray. Diagnostic criteria, however, are fluid in all clinical settings, as rheumatologists will appreciate, and consistency of diagnostic labelling is often no more a demonstrably strong feature of specialist practice than it is in general practice. As long as consultation data such as those in the Linsell paper [1] are interpreted as what the GP regards as shoulder pain, bursitis or capsulitis, then much of value can be taken from data collected in this way. The third issue is that general practice consultation data is only providing a measure of morbidity for which people seek health care. However, there are advantages to this. First, consultation occurrence can be calculated as population rates because each practice has its specified registered population pool from which all consulters come. Second, consultation rates, although underestimating morbidity, are likely to reflect underlying patterns of occurrence of illness in the population, and the more severe and precise the diagnostic syndrome, the more likely this is to be true. Finally, and well illustrated by Linsell et al. [1], general practice data provide one direct measure of health-care use. There are few publications, for example, on the proportion of musculoskeletal patients referred over time from general practice to specialist care, and it is a merit of the Linsell paper that it tackles this. The same concerns about validity apply: are all referrals recorded and are other routes to the specialist (casualty, private clinics) eventually entered in the practice records? Of course, many other routes of referral, such as therapies, may be less well recorded, and few of the many sources of health-care that lie outside the National Health Service (NHS) have established methods of routine recording. It is an incomplete picture, but a picture worth having. The most obvious application of general practice consultation data to musculoskeletal morbidity is in determining the prevalence of symptoms and disease based on persons consulting and on the general practitioner's diagnostic label. Estimates of consultation prevalence for a number of musculoskeletal diseases, such as those provided by the Arthritis Research Campaign [11], are based on the most recent of four national surveys of general practice consultations carried out in 1991/92 (MSGP4 [12]). Such national practice samples are particularly valuable for providing estimates of the prevalence of rarer diseases. Annual prevalence rates are usually defined as the number of people who have consulted about the problem at least once in the year, expressed as a proportion of all the population registered with the practices in the database. These will only pick up patients who consulted with that problem and were given a code for it during that year. Those who have the disease but have not been diagnosed and all others who did not consult for that problem during the year will remain invisible. An alternative is to measure prevalence over a longer period of time by expanding the search to cover several years and include those who only intermittently seek or use primary health-care. However, annual prevalence rates are also useful inasmuch as they provide a picture of current use of primary care for a particular problem. Consultation databases would seem particularly suited to the measurement of incidence, given that the first onset of a problem is likely to be seen and recorded in primary care. A challenge is how to identify a consultation as being ‘first ever’, given that many patients do not have full coded histories on computer databases which may only have been running for a few years. Even if a complete history were available, most musculoskeletal conditions do not have a clear ‘first ever’ onset, and for problems such as back or joint pain it is the onset of a new episode or a recurrence that is likely to be most easily measurable. Use of episode coding (such as the system used to define incident cases in the MSGP4 into ‘first’, ‘new’ or ‘ongoing’) relies on the accuracy of the information obtained and entered by the health-care professional. The alternative is to work on the basis that a patient must have a certain number of years free from consultation for that problem prior to their current consultation. For example, Linsell et al. in their paper in this issue of Rheumatology and their previous publication [1, 2] use a 3-yr time period without a record of consultation for the morbidity to define incident cases of shoulder problems and hip and knee problems. The required number of years may vary from 1 for acute or chronic conditions requiring regular GP services to several for chronic conditions that can be managed by self-care or in secondary care. General practice consultation databases can be used for the longitudinal study of disease. Time trends in the prevalence and incidence of disease have been studied in, for example, diabetes [13]. However, caution is needed as to whether these represent real changes of prevalence or improvements in morbidity recording or changes in diagnostic criteria. More ambitiously, individuals can be followed over time. Registered practice populations are dynamic rather than static as people move in and out of the practice, and, whilst this must be taken into account in following up cohorts of patients within general practice databases, it does not devalue such work. Potential longitudinal analyses include studies of long-term outcomes related to treatment, such as the risk of myocardial infarction in patients taking cyclooxygenase 2 inhibitors and other NSAIDs [14]. It may be possible to follow patients from before the first record of a condition to assess the prior history and predictors of diagnosis and consultation for conditions such as knee osteoarthritis [15]. After diagnosis, treatment and referral patterns can be investigated longitudinally (as Linsell et al. have done with shoulder conditions and hip and knee problems), as can comorbidities [16] and clinical outcomes. Another advantage of population-based consultation data is that they can be linked to other characteristics, such as deprivation. Variation in the prevalence of consultation for rheumatoid disorders in New Zealand by deprivation status has been found [17]. Currently, the linkage of patients to deprivation scores within UK databases is limited, although this has been done in CiPCA and QRESEARCH. Deprivation, for example, has been shown to be associated with lower achievement of quality indicators for diabetes in the QRESEARCH database [18]. There is much potential in the creative and careful use of consultation databases for musculoskeletal research. Indeed, if such databases are routinely anonymized and downloaded as part of quality control and data collection in clinical general practice, they might in the future provide the most enduring measure of morbidity ascertainment, especially as survey research becomes increasingly constrained by ethical considerations and declining response rates. Nurses and therapists and other primary care team members are actively contributing their own coded data to computerized systems, and the recording of secondary care information, such as letters from rheumatology units, is improving, This means that the databases may soon provide a relatively complete picture of NHS health-care use for musculoskeletal disorders. Although there is still some way to go before this is a reality, continuing improvements in the quality of morbidity coding and the amount of information collected mean that general practice consultation databases will remain a rich resource for investigating the occurrence and course of musculoskeletal illness and disease in the community. We are engaged in joint work on the use of general practice consultation data sets for musculoskeletal conditions with colleagues at the ARC Epidemiology Unit in the University of Manchester (Professor Deborah Symmons, Ms Alexandra Clarke), at the RCGP Birmingham Research Unit (Dr Douglas Fleming) and with the CiPCA team at Keele University. The views in the article are our own, but have benefited from discussion with these colleagues. Independent grants from Medical Research Council and NCCRCD have allowed us to investigate the databases concerned (GPRD, RCGP Weekly Returns Service, CiPCA). The authors have declared no conflicts of interest.

OBJECTIVES: Published data were analysed to determine if the use of tumour necrosis factor (TNF) blocking agents in male patients during time of conception is associated with an increased risk of fetal abnormalities or complications during pregnancy. Moreover, we were interested in the impact of TNFblocking agents on sperm quality characteristics. METHODS: We performed a systematic literature review (Medline, online archives of Annual European Congress of Rheumatology and the American College of Rheumatology). One-hundred and thirty-nine Articles of potentially relevant reports were identified and screened for retrieval and nine articles were included in the final analysis. RESULTS: Overall, there were sixty cases, where expectant fathers used TNFblocking agents shortly before conception. The outcomes of the pregnancies are documented in twenty-eight events. We did not find any documentation of miscarriages or physical abnormities associated with TNF blocking treatment and paternity; however, we did find documentation evidence that sperm motility and vitality even may improve under TNF-blocking therapy. This improvement may be caused by a decrease in disease activity. CONCLUSIONS: Published data suggest that TNF-blocking therapy in male patients during time of conception does not increase the risk of adverse pregnancy outcome. In addition TNF-blocking therapy does not appear to reduce male fertility.

OBJECTIVE: To evaluate whether age and renal impairment affect the rate of side effects or expected efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Data was pooled from 11 MTX clinical trials containing 496 patients treated with MTX. We evaluated those patients less than 60 years old and those in 5-year groupings of age over age 60. Using serum creatinine, weight, and age, we calculated creatinine clearance and placed patients into quartiles based on their baseline creatinine clearance. To evaluate efficacy, we used changes in American College of Rheumatology core set efficacy measures available in these trials. To quantify side effects, we scored each side effect based on a modified Fries toxicity score and assigned each patient a score based on the worst side effect experienced during the trial. We also separately evaluated liver toxicities (twice normal elevation of AST or ALT), respiratory toxicity and severe toxicities. Intent-to-treat analyses were performed, adjusting for study of origin. Results were confirmed by placebo controlled trials, comparing MTX and placebo treated patients. RESULTS: Neither age nor renal impairment had any effect on the efficacy of MTX. Those in the oldest age groups (65-69 years, > or = 70 years) were not at higher risk of side effects from MTX. However, patients with renal impairment had a higher overall rate of toxicity and were at higher risk of severe and respiratory toxicities than those whose creatinine clearances were at least 99.8 ml/min (reference group). The odds of severe toxicity were increased roughly 4-fold in those with renal impairment. CONCLUSION: Among clinical trial patients, age does not affect MTX efficacy or the rate of side effects. Renal impairment, however, increases the risk of side effects.

We welcome you to Pediatric Rheumatology, now published by BioMed Central. Pediatric Rheumatology is a continuation of the open access Pediatric Rheumatology Online Journal, launched in 2003 as the first solely pediatric rheumatology journal. Our mission is to further research, scholarship, and education in pediatric rheumatology throughout the world and thereby improve the care of children with arthritis and rheumatic diseases. We hope to speed the growth of pediatric rheumatology in every country. We believe that a dedicated pediatric rheumatology journal has a better opportunity to help develop our field than existing, predominantly adult rheumatology journals. The journal is independent and international and is purposefully free of direct association with any one institution, organization, or commercial enterprise other than BioMed Central. Our choice of the open access venue is intentional. We wish the pediatric rheumatology information in this journal to be freely available to anyone. We believe that this model is optimal for growth of pediatric rheumatology in both developed and developing countries [1,2]. Why is the online, open access venue preferable to the traditional subscription journals in rheumatology? First, all articles become freely and universally accessible online and so an author's work can be read by anyone at no cost. Articles, photos, figures, tables, and other components can be freely downloaded. Second, the authors, not the publishers, hold the copyright for their work and grant anyone the right to reproduce and disseminate the article, as long it is correctly cited and no errors introduced. Third, Pediatric Rheumatology's articles will be archived in PubMed Central, the US National Library of Medicine's full-text repository of life science literature. These articles will also be archived in the repositories at the University of Potsdam in Germany, at INIST in France, the e-Depot, the National Library of the Netherlands' digital archive of all electronic publications, and in the new UK PubMed. Why should we join the shift towards online, open access publishing? The traditional business model for scientific publishers requires restriction of access to published research so that the publishers can recoup the costs of publication. This restriction has deleterious effects, limiting full use of digital technology, and can be considered to be contrary to the interests of authors, funders, and the scientific and medical community as a whole. This traditional system is straining as increasing amounts of research are being published while library budgets have remained static. The open access approach treats publication as the last step in the research process: 1) The article processing charge (APC) covers the cost of publication so that there is free and immediate access to research and education articles. 2) The APCs ensure transparency and allow publishers to compete to provide the best service at the best price. 3) By linking the cost of publication to research budgets, APCs allow the publishing system to adjust to the ever-increasing volume of clinical and basic research [3]. Pediatric Rheumatology is open to submissions on all aspects of pediatric rheumatology, including: editorials; commentaries; research, both clinical and basic; clinical and basic science reviews; rheumatologic reviews for the generalist; significant case series or case reports; book reviews; letters to the editors; and drug studies. Submissions are online, reviews and decisions occur within four weeks in most cases, and publication online is rapid and continuous. We hope that Pediatric Rheumatology will be useful to pediatricians, pediatric rheumatologists, adult rheumatologists, other professionals, and the lay public. Let's work together to help our kids with rheumatic diseases.

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic immunoinflammatory joint disease with a high degree of disability and an unfavorable prognosis.In recent decades, drugs aimed at proinflammatory cytokines, such as tumor necrosis factor (TNF), have been used very often for the treatment of JIA.The effect of these drugs on metabolic processes is not well understood.Objectives: The aim of the study was to study metabolic disorders in children with JIA receiving biological therapy.Methods: 36 children with polyarticular JIA and 20 healthy children were examined in the rheumatology department of the 4th city children's clinical hospital in Minsk.All children with JIA have long received methotrexate, non-steroidal anti-inflammatory drugs and, if necessary, glucocorticoids.In connection with the preservation of a high degree of disease activity during therapy, patients were prescribed adalimumab.All children were determined by the main indicators of the lipid spectrum of the blood.Proteins that make up lipoproteins (apoproteins ApoA, ApoB, ApoE) were determined by the immunoturbidimetric method in the research laboratory of the Belarusian Medical Academy of Postgraduate Education.Statistical data processing was carried out by traditional methods of variation statistics on a personal computer using the program Statsoft Statistica 6.0.Results: In children with JIA, the use of adalimumab showed a significant (p <0.05) decrease in the concentration of ApoA (92.3 [69.7; 99.1] mg / dl) compared with the control group (127.2 [122.1;132.3] mg / dl) and an increase in ApoB (60.9 [48.9; 73.4] mg / dl) compared with the control group (32.1 [19.9; 50.8] mg / dl).The determination of ApoA and ApoB is used to calculate the ApoB / ApoA coefficient, which is a more reliable tool for assessing cardiovascular risk.With the ApoB / ApoA index <1, atherogenicity is regarded as low, with the ApoB / ApoA> 1, atherogenicity increases.ApoB / ApoA> 1 was established in 10 (27.8%) children with JIA.Apolipoprotein E (ApoE) plays an important role in the regulation of lipid metabolism, has a strong antiatherosclerotic effect.There is an assumption that apoE has allele-specific antioxidant abilities.The study found a reduced level of ApoE in the blood serum of children with JIA compared with the control group.During adalimumab treatment, a remission of the disease was achieved.According to the results of a second study of the indicators ApoA, ApoB and ApoE, 6 months after the start of biological therapy, an improvement in these indicators was found.Thus, the content of ApoA increased to 118.9 [113.2;129.4] mg / dL, and the ApoB content decreased to 33.6 [20.8; 49.4] mg / dl.An increase in ApoE to reference values was also noted. Conclusion:The results of the study indicate the likelihood of a reduction in cardiovascular risk in children with JIA in the treatment of adalimumab.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. FINDINGS: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs s1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). INTERPRETATION: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. FUNDING: Bill & Melinda Gates Foundation.

Research Articles| July 23 2009 Standardization of the Leucocyte Migration Test Subject Area: Immunology and Allergy R.N. Maini; R.N. Maini Divisions of Clinical Research and Immunology, Kennedy Institute of Rheumatology, Hammersmith, London Search for other works by this author on: This Site PubMed Google Scholar L.M. Roffe; L.M. Roffe Divisions of Clinical Research and Immunology, Kennedy Institute of Rheumatology, Hammersmith, London Search for other works by this author on: This Site PubMed Google Scholar I.T. Magrath; I.T. Magrath Divisions of Clinical Research and Immunology, Kennedy Institute of Rheumatology, Hammersmith, London Search for other works by this author on: This Site PubMed Google Scholar D.C. Dumonde D.C. Dumonde Divisions of Clinical Research and Immunology, Kennedy Institute of Rheumatology, Hammersmith, London Search for other works by this author on: This Site PubMed Google Scholar International Archives of Allergy and Applied Immunology (1973) 45 (1-2): 308–321. https://doi.org/10.1159/000231048 Article history Published Online: July 23 2009 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation R.N. Maini, L.M. Roffe, I.T. Magrath, D.C. Dumonde; Standardization of the Leucocyte Migration Test. International Archives of Allergy and Applied Immunology 31 December 1973; 45 (1-2): 308–321. https://doi.org/10.1159/000231048 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Archives of Allergy and Applied Immunology Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1973Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

BACKGROUND: The referral of patients with positive anti-nuclear antibody (ANA) tests has been criticized as an inappropriate use of medical resources. The utility of a positive ANA test in a central triage (CT) system was studied by determining the autoantibody profiles and clinical diagnoses of patients referred to rheumatologists through a CT system because of a positive ANA test. METHODS: Patients that met three criteria were included: (1) referred to Rheumatology CT over a three year interval; (2) reason for referral was a "positive ANA"; (3) were evaluated by a certified rheumatologist. The CT clinical database was used to obtain demographic and clinical information and a serological database was used to retrieve specific ANA and/or extractable nuclear antigen (ENA) test results. Clinical information was extracted from the consulting rheumatologist's report. RESULTS: 15,357 patients were referred through the CT system; 643 (4.1%) of these because of a positive ANA and of these 263 (40.9%) were evaluated by a certified rheumatologist. In 63/263 (24%) of ANA positive patients, the specialist provided a diagnosis of an ANA associated rheumatic disease (AARD) while 69 (26.2%) had no evidence of any disease; 102 (38.8%) had other rheumatologic diagnoses and 29 (11%) had conditions that did not meet AARD classification criteria. Of ANA positive archived sera, 15.1% were anti-DFS70 positive and 91.2% of these did not have an AARD. CONCLUSIONS: This is the first study to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA. The spectrum of autoantibody specificities was wide with anti-Ro52/TRIM21 being the most common autoantibody detected. Approximately 15% of referrals had only antibodies to DFS70, the vast majority of which did not have clinical evidence for an AARD. These findings provide insight into the utility of autoantibody testing in a CT system.

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6-8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5-15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities.

The coronavirus disease-2019 (COVID-19) pandemic has unsettled conventional medical education, hastening a switch to digital platforms and open-access publishing. Rheumatology is a fast evolving academic discipline that stands to gain by this switch. Most rheumatology textbooks are now available in digital formats, and these are complemented with live updating educational hubs such as UpToDate and ClinicalKey. Emerging topics of COVID-19 on these proprietary platforms are now freely available to all specialists. Social media channels, particularly Twitter, are becoming major players in the era of COVID-19 by offering online journal clubs, enabling fast dissemination of influential articles, and facilitating interactive education. Indexed rheumatology journals, in turn, aid online education by opening access to recommendations and other materials that are rapidly changing research and practice worldwide. Research peer review additionally offers learning experience to novice and seasoned researchers and authors. Global rheumatology societies have online learning resources, which are changing their format and geographic reach to meet the changing needs in the times of pandemic. While online teaching lacks emotional connections between mentors and mentees, switch to a more interactive format of education and regular contacts may partly solve the issue. Rheumatologists can take the lead in these challenging times and contribute more to online scholarly activities which are aimed to maintain and enrich education. Key Points • Disparities in rheumatology education are likely to be widened during the COVID-19 pandemic. • Barriers to rheumatology education include limited number of instructors and their limited experience in online teaching. • Online textbooks, didactic materials of indexed rheumatology journals, and frequently updated online educational hubs such as UpToDate serve as a foundation of online rheumatology education. • Online rheumatology education is enriched by peer review and social media activities, which are becoming major players in the time of the COVID-19 pandemic.

OBJECTIVE: To assess the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in children with chronic small-to-medium vessel vasculitis. METHODS: A cohort of 574 patients, identified by physician's diagnosis (MD-diagnosis) in A Registry of Childhood Vasculitis, was classified by computation of registry data as having granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA after applying (1) ACR/EULAR AAV criteria and (2) pediatric-adapted European Medicines Agency (Ped-EMA) classification algorithm (incorporating Ankara GPA criteria). Venn diagrams compared the resulting GPA and MPA cohorts with MD-diagnosis. Sensitivity and specificity of criteria for GPA were evaluated against MD-diagnosis. Fisher exact test evaluated differences in the frequencies of individual clinical features in GPA versus MPA. RESULTS: Comparing ACR/EULAR criteria against the Ped-EMA algorithm for classifying AAV, more patients were classified as GPA or MPA (n = 396 vs 360, respectively), fewer had GPA (n = 261 vs 288, respectively), more had MPA (n = 135 vs 72, respectively), and fewer GPA cases coclassified as MPA (12% vs 28%, respectively); there were more differences between GPA and MPA in Pediatric Vasculitis Activity Score-defined clinical features (n = 14 vs 10, respectively). When classifying GPA by ACR/EULAR or Ankara criteria, sensitivity (74.5% vs 72.1%, respectively) was comparable, and specificity for ACR/EULAR criteria (93.9% vs 79.9%, respectively) was improved. CONCLUSION: The 2022 ACR/EULAR classification criteria for AAV perform at least as well as previous pediatric criteria and provide categorical MPA criteria where none existed previously; the criteria for GPA and MPA now specifically differentiate each other, with more differences between them in the frequencies of clinical features. Our findings support the preferential use of ACR/EULAR over Ankara criteria for GPA in pediatrics.

Financial and Competing Interests: DPM is an Associate Editor of Rheumatology International, Associate Editor of Indian Journal of Rheumatology and editorial board member of Clinical Rheumatology, Mediterranean Journal of Rheumatology, Archives of Rheumatology, African Journal of Rheumatology and Central Asian Journal of Medical Hypotheses and Ethics. VR is the Editor-in-Chief of the Journal of the Royal College of Physicians of Edinburgh ( JRCPE). This paper has undergone peer review in accordance with JRCPE's policies. VR is also Emeritus Editor of the Indian Journal of Rheumatology and an editorial board member of Rheumatology Advances in Practice (Oxford)

To identify the core journals of evidence-based physiotherapy practice we conducted an analysis of the Physiotherapy Evidence Database (PEDro), the most comprehensive database of physiotherapy clinical trials and systematic reviews. We compared our results to two earlier lists of core journals based upon citation analyses and rankings from the Institute for Scientific Information (ISI) impact factors. As of 2 June 2000 the PEDro database contained 2,231 papers that had been published in 519 different journals with a single journal contributing from 1 to 109 papers. When journals were ranked based upon the total number of papers contributed to PEDro the top five journals were: Archives of Physical Medicine and Rehabilitation, British Medical Journal, Spine, Physical Therapy, and Cochrane Database of Systematic Reviews. However when the journals were ranked based upon the average methodological quality of clinical trials the top five were: British Journal of Obstetrics and Gyn aecology, New England Journal of Medicine, Stroke, Scandinavian Journal of Rheumatology, and British Journal of Rheumatology. When judged by trial quality, the top five exclusively physiotherapy journals were Australian Journal of Physiotherapy, Physiotherapy Theory and Practice, Physical Therapy, Physiotherapy, and Physiotherapy Canada. Each approach to ranking the journals produced a different set and ranking of core journals to that of the two previous citation analyses. The current study's rankings were unrelated to ISI impact factors.

Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity. This guideline builds on and widens the recommendations developed for the first guideline published in 2017. We have included advice on the management of children and adolescents where appropriate to provide a comprehensive guideline for UK-based rheumatology teams.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

BACKGROUND: To measure the use, satisfaction and impact of a web portal which provides patients with rheumatoid arthritis home access to their electronic medical records (EMR). METHODS: A pretest-posttest study was conducted among 360 patients. Questionnaires assessed socio-demographics, health literacy, Internet use, disease characteristics, patient-provider relationship and empowerment before and after launching a hospital-based patient web portal. To measure the impact of the portal, patients' satisfaction with care, trust in their rheumatologist, self-efficacy in patient-provider communication, illness perceptions, and medication adherence were assessed. The post-test included questions on portal use, satisfaction, and self-perceived impact due to portal use. RESULTS: 54% of respondents with Internet access had viewed their EMR. Respondents were positive about the ease of use and usefulness of the portal and reported very few problems. Age (P = .03), amount of Internet use (P = .01) and self-perceived Internet skills (P = .03) significantly predicted portal use. Of the respondents who had logged in, 44% reported feeling more involved in their treatment and 37% felt they had more knowledge about their treatment. Significant differences over time were not found on the empowerment-related instruments. CONCLUSIONS: The current portal succeeded in offering patients access to their EMR in a usable and understandable way. While its true impact is difficult to grasp, a relevant portion of the patients felt more involved in their treatment due to the web portal. Offering patients home EMR access, therefore, appears to be a valuable addition to the care process.

OBJECTIVES: To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region. DESIGN: Case-control and cohort diagnostic accuracy study. METHODS: In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region. RESULTS: The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%). CONCLUSIONS: AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.

Telehealth is an extraordinary advancement of modern medicine. It has increased access to care for underserved populations and, in the case of pediatric rheumatology, has expanded the reach of a limited work force. During the Coronavirus Disease 2019 (COVID-19) pandemic, telehealth has radically changed the way healthcare workers have been able to deliver care while maintaining social distance. In addition to the infectious havoc of COVID-19, the pandemic has further altered the psychosocial milleu of our society which directly impacts the wellness and safety of our pediatric rheumatology patients. These psychosocial factors may be difficult to assess and triage solely using telehealth. The objective of this short review is to educate practitioners on the psychosocial concerns exacerbated by the COVID-19 pandemic and to discuss the possible hurdles in utilization of telehealth to care for our vulnerable patient population.

After decades of basic research with many setbacks, artificial intelligence (AI) has recently obtained significant breakthroughs, enabling computer programs to outperform human interpretation of medical images in very specific areas. After this shock wave that probably exceeds the impact of the first AI victory of defeating the world chess champion in 1997, some reflection may be appropriate on the consequences for clinical imaging in rheumatology. In this narrative review, a short explanation is given about the various AI techniques, including 'deep learning', and how these have been applied to rheumatological imaging, focussing on rheumatoid arthritis and systemic sclerosis as examples. By discussing the principle limitations of AI and deep learning, this review aims to give insight into possible future perspectives of AI applications in rheumatology.