A biophysical limit for quorum sensing in biofilms.

Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms AI production should be a protected function not directly tied to metabolism.

The Global Spine Care Initiative: resources to implement a spine care program.

PURPOSE: The purpose of this report is to describe the development of a list of resources necessary to implement a model of care for the management of spine-related concerns anywhere in the world, but especially in underserved communities and low- and middle-income countries. METHODS: Contents from the Global Spine Care Initiative (GSCI) Classification System and GSCI care pathway papers provided a foundation for the resources list. A seed document was developed that included resources for spine care that could be delivered in primary, secondary and tertiary settings, as well as resources needed for self-care and community-based settings for a wide variety of spine concerns (e.g., back and neck pain, deformity, spine injury, neurological conditions, pathology and spinal diseases). An iterative expert consensus process was used using electronic surveys. RESULTS: Thirty-five experts completed the process. An iterative consensus process was used through an electronic survey. A consensus was reached after two rounds. The checklist of resources included the following categories: healthcare provider knowledge and skills, materials and equipment, human resources, facilities and infrastructure. The list identifies resources needed to implement a spine care program in any community, which are based upon spine care needs. CONCLUSION: To our knowledge, this is the first international and interprofessional attempt to develop a list of resources needed to deliver care in an evidence-based care pathway for the management of people presenting with spine-related concerns. This resource list needs to be field tested in a variety of communities with different resource capacities to verify its utility. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: classification system for spine-related concerns.

PURPOSE: The purpose of this report is to describe the development of a classification system that would apply to anyone with a spine-related concern and that can be used in an evidence-based spine care pathway. METHODS: Existing classification systems for spinal disorders were assembled. A seed document was developed through round-table discussions followed by a modified Delphi process. International and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. RESULTS: Thirty-six experts from 15 countries participated. After the second round, there was 95% agreement of the proposed classification system. The six major classifications included: no or minimal symptoms (class 0); mild symptoms (i.e., neck or back pain) but no interference with activities (class I); moderate or severe symptoms with interference of activities (class II); spine-related neurological signs or symptoms (class III); severe bony spine deformity, trauma or pathology (class IV); and spine-related symptoms or destructive lesions associated with systemic pathology (class V). Subclasses for each major class included chronicity and severity when different interventions were anticipated or recommended. CONCLUSIONS: An international and interprofessional group developed a comprehensive classification system for all potential presentations of people who may seek care or advice at a spine care program. This classification can be used in the development of a spine care pathway, in clinical practice, and for research purposes. This classification needs to be tested for validity, reliability, and consistency among clinicians from different specialties and in different communities and cultures. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: model of care and implementation.

PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions. METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps. RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up. CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: methodology, contributors, and disclosures.

PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations. METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care. RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest. CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: World Spine Care executive summary on reducing spine-related disability in low- and middle-income communities.

PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources. METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders. RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care. CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: care pathway for people with spine-related concerns.

PURPOSE: The purpose of this report is to describe the development of an evidence-based care pathway that can be implemented globally. METHODS: The Global Spine Care Initiative (GSCI) care pathway development team extracted interventions recommended for the management of spinal disorders from six GSCI articles that synthesized the available evidence from guidelines and relevant literature. Sixty-eight international and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. An iterative consensus process was used. RESULTS: After three rounds of review, 46 experts from 16 countries reached consensus for the care pathway that includes five decision steps: awareness, initial triage, provider assessment, interventions (e.g., non-invasive treatment; invasive treatment; psychological and social intervention; prevention and public health; specialty care and interprofessional management), and outcomes. The care pathway can be used to guide the management of patients with any spine-related concern (e.g., back and neck pain, deformity, spinal injury, neurological conditions, pathology, spinal diseases). The pathway is simple and can be incorporated into educational tools, decision-making trees, and electronic medical records. CONCLUSION: A care pathway for the management of individuals presenting with spine-related concerns includes evidence-based recommendations to guide health care providers in the management of common spinal disorders. The proposed pathway is person-centered and evidence-based. The acceptability and utility of this care pathway will need to be evaluated in various communities, especially in low- and middle-income countries, with different cultural background and resources. These slides can be retrieved under Electronic Supplementary Material.

Pain management in rheumatology research, training, and practice.

The Pain Management Task Force of the American College of Rheumatology published a report in 2010 highlighting pain management as a fundamental aspect of clinical practice, training and research. In the interim, the consideration of pain as a focus of attention of rheumatologists and rheumatology health professionals has become even more challenging than in 2010 because of the epidemic of opiate addiction and overdose death. The characterisation of categories of pain by mechanism (e.g., inflammation, joint degeneration, abnormalities of central pain processing) can help guide treatment. However, such categorisation can overlook the overlap of these processes and their interaction to create mixed pain states. Further complicating the assessment of pain, outcome measures in rheumatic disease often assess the degree of pain indirectly while concentrating on the quantification of inflammation. Non-inflammatory pain often persists despite treatment, highlighting the need for alternative analgesic therapies. Recommended therapies include acetaminophen, nonsteroidal anti-inflammatory drugs, and stimulators of the pain inhibitory pathway. Each of these non-opioid therapies has incomplete efficacy and potential toxicities that can limit their utility. Non-pharmacologic therapies can show efficacy that rivals or surpasses pharmacologic therapies in the control of pain and improving function in a variety of rheumatic disorders including chronic low back pain and fibromyalgia. A limitation of the use of these therapies is inadequate training and appreciation of their benefits. Furthermore, the supply of trained practitioners to provide non-pharmacological care and support patient efforts for self-management is often limited. Together, these considerations suggest the importance of a renewed effort to implement task force recommendations.

Established Microbial Colonies Can Survive Type VI Secretion Assault.

Type VI secretion (T6S) is a cell-to-cell injection system that can be used as a microbial weapon. T6S kills vulnerable cells, and is present in close to 25% of sequenced Gram-negative bacteria. To examine the ecological role of T6S among bacteria, we competed self-immune T6S+ cells and T6S-sensitive cells in simulated range expansions. As killing takes place only at the interface between sensitive and T6S+ strains, while growth takes place everywhere, sufficiently large domains of sensitive cells can achieve net growth in the face of attack. Indeed T6S-sensitive cells can often outgrow their T6S+ competitors. We validated these findings through in vivo competition experiments between T6S+ Vibrio cholerae and T6S-sensitive Escherichia coli. We found that E. coli can survive and even dominate so long as they have an adequate opportunity to form microcolonies at the outset of the competition. Finally, in simulated competitions between two equivalent and mutually sensitive T6S+ strains, the more numerous strain has an advantage that increases with the T6S attack rate. We conclude that sufficiently large domains of T6S-sensitive individuals can survive attack and potentially outcompete self-immune T6S+ bacteria.

Report of the NIH Task Force on research standards for chronic low back pain.

OBJECTIVE: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. DESIGN: Expert panel and preliminary evaluation of key recommendations. METHODS: The NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. RESULTS: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. CONCLUSION: The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document, and undergo continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes.

Focus article: report of the NIH Task Force on Research Standards for Chronic Low Back Pain.

UNLABELLED: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes.

Report of the National Institutes of Health task force on research standards for chronic low back pain.

OBJECTIVES: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. METHODS: The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. RESULTS: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. CONCLUSIONS: The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement.

Low Back Pain in Adolescent and Geriatric Populations.

Spinal pain is the most common form of musculoskeletal pain. Chronic low back pain may contain nociceptive, neuropathic, and central components. Children are at risk of developing spinal pain. An increasing proportion of children develop low back pain as they become adolescents. In most adolescents, no specific diagnosis is identified. Psychological factors play a role in adolescents with back pain. Lumbar spinal stenosis causes neurogenic claudication in older patients. Magnetic resonance imaging is the best radiographic technique to detect nerve compression. Surgical decompression with or without fusion may offer greater short-term benefit but may not be significantly better than medical therapy.

Comparison of the history and physical examination for hip osteoarthritis and lumbar spinal stenosis.

BACKGROUND: Leg pain associated with walking is sometimes incorrectly attributed to hip osteoarthritis (OA) or lumbar spinal stenosis (LSS). PURPOSE: This study compared physicians' values of signs and symptoms for diagnosing and differentiating hip OA and LSS to their clinical utility. STUDY DESIGN/SETTING: Musculoskeletal physicians were surveyed with online questionnaires. Patients were recruited from hip and spine specialty practices. PATIENT SAMPLE: Seventy-seven hip OA and 79 LSS patients. OUTCOME MEASURES: Signs and symptoms of hip OA and LSS. METHODS: Fifty-one of 66 invited musculoskeletal physicians completed online surveys about the values of 83 signs and symptoms for diagnosing hip OA and LSS. Of these, the most valued 32 symptoms and 13 physical examination items were applied to patients with symptomatic hip OA or LSS. Positive likelihood ratios (+LR) were calculated for each items' ability to differentiate hip OA from LSS, with a +LR>2 set as indicating usefulness for favoring either diagnosis. Positive LRs were compared with surveyed physicians' values for each test. RESULTS: All symptoms were reported by some patients with each diagnosis. Only 11 of 32 physician-valued symptoms were useful for discriminating hip OA from LSS. Eight symptoms favored hip OA over LSS: groin pain (+LR=4.9); knee pain (+LR=2.2); pain that decreased with continued walking (+LR=3.9); pain that occurs immediately with walking (+LR=2.4); pain that occurs immediately with standing (+LR=2.1); pain getting in/out of a car (+LR=3.3); pain with dressing the symptomatic leg (+LR=3.1); and difficulty reaching the foot of the symptomatic leg while dressing (+LR=2.3). Three symptoms favored LSS over hip OA: pain below the knee (+LR=2.3); leg tingling and/or numbness (+LR=2.7); and some pain in both legs (+LR=2.5). Notable symptoms that did not discriminate hip OA from LSS included: pain is less while pushing a shopping cart (+LR=1.0); back pain (+LR=1.1); weakness and/or heaviness of leg (+LR=1.1); buttocks pain (+LR=1.2); poor balance or unsteadiness (+LR=1.2); pain that increased with weight-bearing on the painful leg (+LR=1.3), and step to gait on stairs (+LR=1.7). Consistent with physicians' expectations, 7 of 13 physical examination items strongly favored hip OA over LSS: limited weight-bearing on painful leg when standing (+LR=10); observed limp (+LR=9); and painful and restricted range-of-motion with any of five hip maneuvers (+LR range 21-99). Four of five tested neurological deficits (+LR range 3-8) favored the diagnosis of LSS over hip OA. CONCLUSIONS: There is substantial crossover of symptoms between hip OA and LSS, with some physician-valued symptoms useful for differentiating these disorders whereas others were not. Physicians recognize the value of the examination of gait, the hip, and lower extremity neurological function for differentiating hip OA from LSS. These tests should be routinely performed on all patients for which either diagnosis is considered. Awareness of these findings might reduce diagnostic errors.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

Chronic low back pain in a working-age adult.

Low back pain is an extremely common patient complaint. Most cases resolve fairly quickly after the acute episode. However, a small but significant number of patients develop chronic low back pain; a persistent disabling condition. Patients suffer from unremitting pain and often become functionally impaired. Multiple patient characteristics have been identified that place patients at risk for developing chronic low back pain. Currently, it is difficult to find clinical guidelines on how best to manage chronic low back pain, and it remains a substantial treatment challenge for both physicians and patients. The causes, risk factors, prognosis and treatment strategies for chronic low back pain will be discussed in this chapter. The evidence regarding different pharmacological and non-pharmacological treatment modalities will be reviewed and a logical, focused treatment strategy will be outlined.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.