Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts

Objective We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. Design The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. Results Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. Conclusion Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used causespecific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24.98-30.15 million). From 1990 to 2016, the agestandardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6.0-10.4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments.Published versionWe acknowledge the funding and support of the Bill & Melinda Gates Foundation. AK was supported by the Miguel Servet contract, which was financed by the CP13/00150 and PI15/00862 projects integrated into the National Research, Development, and Implementation, and funded by the Instituto de Salud Carlos III General Branch Evaluation and Promotion of Health Research and the European Regional Development Fund (ERDF-FEDER). AMS is supported by the Egyptian Fulbright Mission Program. AF acknowledges the Federal University of Sergipe (Sergipe, Brazil). AA received financial assistance from the Indian Department of Science and Technology (New Delhi, India) through the INSPIRE faculty programme. AS is supported by Health Data Research UK. DJS is supported by the South African Medical Research Council. AB is supported by the Public Health Agency of Canada. SMSI received a senior research fellowship from the Institute for Physical Activity and Nutrition, Deakin University (Waurn Ponds, VIC, Australia), and a career transition grant from the High Blood Pressure Research Council of Australia. FP and CF acknowledge support from the European Union (FEDER funds POCI/01/0145/FEDER/007728 and POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia, and Ministério da Educação e Ciência) under the Partnership Agreements PT2020 UID/MULTI/04378/2013 and PT2020 UID/QUI/50006/2013. TB acknowledges financial support from the Institute of Medical Research and Medicinal Plant Studies, Yaoundé, Cameroon. AM of Imperial College London is grateful for support from the Northwest London National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care and the Imperial NIHR Biomedical Research Centre. KD is funded by a Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine (grant number 201900). PSA is supported by an Australian National Health and Medical Research Council Early Career Fellowship. RT-S was supported in part by grant number PROMETEOII/2015/021 from Generalitat Valenciana and the national grant PI17/00719 from ISCIII-FEDER. The Serbian part of this contribution (by MJ) has been co-financed with grant OI175014 from the Serbian Ministry of Education, Science and Technological Development; publication of results was not contingent upon the Ministry’s approval. MMMSM acknowledges support from the Serbian Ministry of Education, Science and Technological Development (contract 175087). MM’s research was supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust (London, UK) and King’s College London. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. TWB was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt professor award, which was funded by the German Federal Ministry of Education and Research