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Introduction The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Objectives To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. Methods A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm2) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. Results Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. Conclusions Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

The objective of this paper is to provide an overview of the strengths, limitations and lessons learned from estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It should be read in conjunction with the other GBD 2010 Study papers published in this journal. The strengths of the GBD 2010 Study include: the involvement of a MSK expert group; development of new and more valid case definitions, functional health states, and disability weights to better reflect the MSK conditions; the extensive series of systematic reviews undertaken to obtain data to derive the burden estimates; and the use of a new, more advanced version of the disease-modelling software (DisMod-MR). Limitations include: many regions of the world did not have data; the extent of heterogeneity between included studies; and burden does not include broader aspects of life, such as participation and well-being. A number of lessons were learned. Ongoing involvement of experts is critical to ensure the success of future efforts to quantify and monitor this burden. A paradigm shift is urgently needed among global agencies in order to alleviate the rapidly increasing global burden from MSK conditions. Prevention and control of MSK disability are required, along with health system changes. Further research is needed to improve understanding of the predictors and clinical course across different settings, and the ways in which MSK conditions can be better managed and prevented.

Background Rheumatic diseases are underdiagnosed in the Middle East. Screening and awareness campaigns can be used in conjunction with peripheral ultrasound machines used to screen for low bone mass are a cheaper and more practical option than a whole body dual-energy X-ray absorptiometry. Objectives We proposed to scan a population of a walk-in bone health clinic to aid in the diagnosis of rheumatic diseases such as osteoporosis, inflammatory arthritis, inflammatory back pain and connective tissue disease. Furthermore, we aimed to ascertain if a peripheral heel ultrasound can be used to identify patients at high risk of bone fracture or in need of treatment. Methods Data were gathered from a walk in clinic, part of the Healthy Bone and Joints Campaign at the third level, public hospital in the United Arab Emirates. Screening for osteoporosis, inflammatory arthritis, back pain and other inflammatory arthropothies was undertaken. The patient questionnaire was developed by the rheumatology team with the design based on clinical practice as well as recommendations from internationally-recognised societies (FRAX and ASAS) and textbooks (Kelley) in regards to screening questions for the possible diagnosis. Heel scan was performed using the Achilles™ EXPII (General Electric Company) ultrasonometer. Participants were categorised, based on a Swiss study that established quality assurance procedures for quantitative ultrasound, with an upper threshold of 78% on the stiffness index (SI) reading and lower threshold of 57% (SI), so that the rate of false positives and false negatives were 10%, when DXA was used as the gold standard for diagnosis1. Results The cohort was comprised 232 individuals from 25 different nationalities, with mean age (±SD) of 40.6 (12.2) years, 64.2% were female, and 65.4% were staff members at the hospital. The cohort had a mean number of clinical risk factors (smoking, prior fracture, early menopause, no exercise and oral steroids) of 0.9. Forty four (19%) of the population had two or more of these strong predictors of osteoporosis. There were a total of 156 different referrals to other hospital services with the most common being musculoskeletal ultrasound (n=37), followed by first rheumatology appointment (n=35), physiotherapy (n=25), blood tests (n=24) and central DXA (n=12). Of interest are new diagnoses of osteoarthritis (n=5), osteoporosis (n=2), rheumatoid arthritis (n=1) and ankylosing spondylitis (n=1). Upon categorisation based on the SI thresholds, 184 (84%) were low risk, 29 (13%) intermediate risk and 7 (3%) high risk. Within these groups there were a total of 4 (2.2%), 5 (17%), 3 (43%) of people sent for central DXA from the low, intermediate and high risk groups respectively. Conclusions This is the first such study undertaken in the UAE. The implementation and delivery of a screening campaign to screen for osteoporosis, inflammatory arthritis, inflammatory back pain and connective tissue disease and to increase the awareness and educate patients about the diseases was well received. This working screening campaign will now be improved and taken away from the hospital setting targeting the general population in areas where specialist healthcare and central DXA is not readily available. References Hans et al. Osteoporos Int 2003 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5126

Background Diagnostic discordance for osteoporosis is the presence of different T-scores in two skeletal sites in the same subject leading to different WHO diagnostic categories. Discordance is defined as minor when the difference between two sites is no more than one WHO diagnostic class and major when one site is osteoporotic and the other is normal. Objectives To determine the percentage of minor and major diagnostic discordance and identify associated factors in patients from the United Arab Emirates (UAE) diagnosed with osteoporosis. Methods All patients born in North Africa-Middle East region (as per WHO classification) ≥50 years old seen in rheumatology clinics of our tertiary level hospital from 2011 to 2013, diagnosed with osteoporosis were identified through an internal audit. Details of the first Dual-X-Ray-Absorptiometry test (DXA) during the study period were extracted, including weight, height, T score at femoral neck and total hip in the right side (RFN, RTH) and left side (LFN,LTH) and T score at lumbar spine (LS). Differences in T scores and degree of discordance between sites were calculated. Age, weight, height and BMI were analysed as contributing factors. Results One hundred and seventy-one patients with osteoporosis and DXA test were identified. The mean age was 64.4 (±9.4 SD) and 142 (83%) were females. Diagnostic agreement among all skeletal sites was found in only 16% of patients. Of the cohort, 42% showed one major discordance and 65% showed minor discordance. Maximum concordance was found between RTH and LTH (80%) and minimum between LS and LTH (26%). Minor discordance was present in about half of the patients when comparing spine to any hip site, and in around one quarter when comparing ipsilateral TH and FN sites. Major discordance in LS compared to hip locations was present almost in one third of the patients. Of the four possible spine-hip comparisons, between 89 and 91% of the discordant cases exhibited LS scores lower than the respective hip site. No significant correlation with age, weight, height or BMI was found for the degree of discordance. Conclusions Major and minor spine-hip diagnostic discordance is higher in patients from UAE diagnosed with osteoporosis compared to that reported elsewhere1,2. Inter-hip discordance is compatible with previous data3. Multiple-site measurements seem mandatory not to miss patients at high risk for osteoporosis. References Gnudi S et al, J Clin Densitom 2000 Mounach A et al, Seminars Arthritis Rheum 2009 Hamdy R et al, Osteoporos Int 2006 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4325

Background The use of interferon gamma-release assays (IGRA) has become a very useful tool in the detection of latent tuberculosis (LTB) among patients on biological disease modifying anti-rheumatic drugs (bDMARDs). The IGRA offers some advantages over the intradermal tuberculin skin test (TST), such as, no requirement to re-schedule the patient for the test reading, the elimination of the inter-reader variability and higher specificity. These features facilitate the decision making when deciding which patients require tuberculosis (TB) chemoprophylaxis before starting bDMARDs, particularly in world regions with high incidence of vaccinated individuals and new TB cases. In our tertiary level hospital, the IGRA QuantiFERON-TB Test® (Cellestis Ltd, Australia), was introduced as routine screening test for LTB in late 2008 together with the usual chest X-ray, initially run concurrently and then substituting the old TST in most of the cases. Objectives In this report, we present the benefits of its use in decreasing the number of active TB cases among rheumatoid arthritis (RA) patients prescribed bDMARDs in our centre. Methods An audit was undertaken through the electronic medical record system of our hospital, which was implemented from January 2011 for all medical documentation. All RA patients aged 18 and over seen in the rheumatology outpatient clinic between Jan 2011 and September 2013 and on bDMARDs at any time during this period were identified. Among the cohort of RA patients on bDMARDs, we searched for patients with diagnosis of active TB or receiving anti-TB triple/quadruple therapy. Results were compared to previous RA cohort from the same hospital from the period 2003-2008, which was facilitated by two of the authors of this present paper who worked in our hospital during this period. Results Ninety-seven individuals diagnosed with RA and treated with any of the bDMARDs available during the study period were found. There were no documented cases of TB or active TB treatment among the 97 individuals on bDMARDs during the 34-month audit period. This contrasts with the three cases of TB reactivation among the 86 patients who received bDMARDs in our centre from 2003 to 2008. Conclusions Our data suggest that the IGRA QuantiFERON-TB Test® is more useful than the TST for the LTB screening in adult population on bDMARDs. This is particularly important in mixed populations with a high percentage of individuals being nationals from endemic countries in TB. Our recommendation is to systematically use IGRA in such settings, repeating this on an annual basis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5158

Background: Early treatment initiation is one of the strongest predictors of good treatment response in axial spondyloarthritis (axSpA). Recently, the Assessment in SpondyloArthritis International Society (ASAS) defined early axSpA as a diagnosis of axSpA with a duration of axial symptoms equal to or less than 2 years. Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of ankylosing spondylitis. Objectives: Compare the efficacy and safety of tofacitinib versus placebo (both on non-steroidal anti-inflammatory drug (NSAID) background) in patients with active early axSpA and inadequate response to at least one NSAID. Design: This is a phase IV, randomized, double-blind, placebo-controlled, multicenter clinical trial. Methods and analysis: The study will recruit 104 patients aged ⩾18 and ⩽45 years with active early axSpA (chronic back pain ⩽2 years), inadequate response to at least one NSAID, and objective signs of active inflammation (on magnetic resonance imaging (MRI) of sacroiliac joints (SIJs) or elevated C-reactive protein). Patients will be randomized 1:1 to receive tofacitinib 5 mg twice daily or placebo, with background naproxen 500 mg twice daily for 16 weeks. Patients not meeting early treatment response criteria at week 4 will receive open-label tofacitinib until week 16. Primary and key secondary endpoints at week 16 will be the proportion of patients achieving disease remission (Axial Spondyloarthritis Disease Activity Score <1.3) and change from baseline in MRI SIJ Spondyloarthritis Research Consortium of Canada osteitis score, respectively. Safety will be monitored up to 4 weeks after the last study drug dose. Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and will be approved by independent ethics committees of each center. Discussion: This is one of the first randomized clinical trials designed to evaluate the efficacy and safety of a JAK inhibitor in the recently ASAS-defined “early” axSpA population. Trial registration: ClinicalTrials.gov: NCT06112665; CTIS: 2023-505050-18-00.

The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Bill & Melinda Gates Foundation.

The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Bill & Melinda Gates Foundation.

BackgroundRoad traffic accidents (RTAs) are the second leading injury health burden and cause of death in Europe, after falls (1). A significant but as yet unreported proportion of such burden is potentially due to low bone mineral density (BMD), especially among older people, through its relationship with fractures.ObjectivesTo measure the percentage of deaths, disability-adjusted life years (DALYs) and years lived with disability (YLDs) due to RTA in people aged 50 years and above attributable to low BMD in the European population for the year 2015.MethodsThe estimates followed the Counterfactual Risk Assessment Methodology used in the GBD study (1). Systematic review was performed seeking population-based studies with femoral neck BMD (FNBMD) measured by Dual-X-Ray-Absorptiometry in people 50 years and over. Age- and sex- specific levels of mean +/-SD FNBMD (g/cm2) were extracted from eligible studies, and this was used as the exposure variable. The age and sex-specific 99th percentile from non-Hispanic whites in National Health and Nutrition Examination Survey (NHANES) 2009–2010 was used as theoretical minimum risk factor exposure distribution, to estimate the potential impact fraction (PIF) of FNBMD for fractures. Relative risks of FNBMD for fractures were obtained from a previous meta-analysis (2). Attributable deaths due to RTA-related fractures were obtained through coded hospital data. Disability levels were established by applying disability weights to each type of fracture. Then, PIFs were applied to obtain attributable deaths and disability due to low BMD.ResultsIn the European population aged 50–69 and 70 years and above, 10.8% (95% CI: 8.9–12.4%) and 30.9% (29.1–32.4%) of RTA-related deaths, respectively, were attributable to low BMD. In the age group 50–69 this was the second most important risk factor following alcohol use and in those 70 years and above became the most important risk factor, with double the weight of alcohol use. This represents 2,537 and 5,460 absolute deaths in those aged 50–69 and 70 years and above, respectively. The percentage of health burden and disability caused by RTAs attributable to low BMD grew steadily from the ages of 50 and onwards.ConclusionsThis data shows the non-previously reported important role of low BMD as a preventable risk factor for European RTAs' health burden in population 50 years and over, which requires urgent attention.References Forouzanfar et al. Lancet 2016.Johnell et al. JBMR 2005. Disclosure of InterestNone declared