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Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR)., Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated., Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care., Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR., Competing Interests: Competing interests: KKK: Research grants from Independent Research Fund Denmark, Danish Rheumatic Association and Central Denmark Region unrelated to this project. SES: Research grants from Rheumatology Research Foundation, Bristol Myers Squibb Foundation. Clinical trial support from AstraZeneca, GlaxoSmithKline; Consulting fees from Sanofi (funds toward research support); Data Safety Monitoring Board on MINT trial, Advisory Board for Sanofi (funds toward research support). E-MH: Has received grants unrelated to this manuscript from Novo Nordic Foundation, Roche, Novartis; Personal fees from AbbVie, Sanofi, SOBI, Merck Sharp & Dohme and Union Chimique Belge. AD: Consulting fees from Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi; Board member Vasculitis Foundation. LN: Has received Honorarium from Abbvie; Trustee of the charity PMR-GCA Scotland. SM: Consulting fees from Astrazeneca; Honoraria from Vifor. KJW: Grants from Eli Lilly, Kiniksa, BMS; Consulting fees from Amgen, Sanofi. Honoraria from Amgen. CP: Consulting fee from Pfizer. MP: Consulting fee from Novartis; Clinical trial participant for Abbvie, Amgen, AstraZeneca. HIK: Honoraria from Roche, eTherapeutic Guidelines Australia; Board member Australian Rheumatology Association; Clinical trials for Roche, Abbvie, Sun, Emerald, Novartis, Biogen, Sanofi, Syneos. CEO: Consultancy for Abbvie; Speaking honoraria from Abbvie, Janssen, Novartis and Roche; Advisory board for Abbvie. WAS: Has received honoraria from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi ; Support for attending meetings/travel from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi; Participated in advisory board from Abbvie, GlaxoSmithKline, Novartis, Sanofi; Principle investigator of phases 2 and 3 studies sponsored by Abbvie, GlaxoSmithKlinie, Novartis and Sanofi. EBrouwer: As an employee of the UMCG received a speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands in 2023 which was paid to the UMCG; As an employee of the UMCG received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514 which were paid to the UMCG. SM: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SM is supported in part by the NIHR Leeds Biomedical Research Centre. VD-P has received honorarium from Abbvie, Chugai, Novartis, BMS, Support for attending meetings/travel from Novartis; Participated in advisory borad from Abbvie, Novartis. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused on highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS-associated somatic variants and their disease penetrance in a diverse, unselected population., Methods: We analyzed clinical-grade whole genome sequencing data from 245,368 participants in the All of Us Research Program. We compared persons carrying a canonical VEXAS-associated somatic variant to age, sex, and ancestry matched controls across the domains of diagnoses, medications, and laboratory values., Results: 74 participants were identified who carry one VEXAS-defining somatic variant, UBA1 c.121A>C, p.Met41Leu. The variant allele fraction ranged from 4.5% to 33%. No other canonical VEXAS-associated variants were identified. Of the 74 carriers, 62 (84%) were women, 20 (27%) were African American, and 14 (19%) were American Admixed/Latino. There was no statistically significant association between case/control status and any VEXAS-associated diagnosis code, medication prescription, or laboratory value., Conclusion: We report the largest cohort to date of persons with the VEXAS-associated p.Met41Leu somatic variant. This cohort differed substantially from reported cohorts of patients with clinical VEXAS, having a higher proportion of persons who were young, female, and of diverse ancestry. Variant allele fractions were lower than reported in clinical VEXAS cohorts, and bioinformatic analysis detected no clinical manifestations of VEXAS. Thus, the UBA1 p.Met41Leu somatic variant displayed incomplete penetrance for VEXAS. Further study is needed to determine the natural history of VEXAS-associated somatic variants in the predisease phase., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The finding of aortitis, often incidentally noted on surgical resection, should prompt evaluation for secondary causes including large-vessel vasculitis. In a large proportion of cases, no other inflammatory cause is identified and the diagnosis of clinically isolated aortitis is made. It is unknown whether this entity represents a more localized form of large-vessel vasculitis. The need for immunosuppressive therapy in patients with clinically isolated aortitis remains unclear. Patients with clinically isolated aortitis warrant imaging of the entire aorta at baseline and regular intervals because a significant proportion of patients have or develop abnormalities in other vascular beds., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries. Several key events have shaped the current spectrum of the disease including the separation of a subgroup with microscopic polyangiitis, the discovery of the association of hepatitis B, and the discovery of adenosine deaminase 2 deficiency (DADA2). With the discovery of secondary causes of PAN and changing nomenclature, the incidence of PAN has declined over time. Common manifestations include constitutional symptoms, skin involvement, peripheral neuropathy, gastrointestinal disease, and renal involvement. DADA2 is a genetic cause of medium vessel vasculitis that is important to distinguish from primary PAN as treatment with TNF inhibitors can prevent morbidity and mortality in those with a vasculitis phenotype. Treatment of systemic primary PAN involves the use of systemic immunosuppressive therapy largely guided by the severity of disease. With current treatment regimens, the prognosis has changed from a once uniformly fatal disease to a 5-year survival rate above 80%.

Systemic vasculitis can be a challenge to differentiate from other forms of vasculopathy. Because treatment for systemic vasculitis is disparate from that for other forms of vasculopathy, clinicians should strive for high diagnostic certainty. This review article aims to highlight the clinical, radiographic, and histologic clues to distinguish systemic vasculitis from mimics. Vasculitis should be considered in patients with preexisting conditions including autoimmune connective tissue diseases, multisystem manifestations, unexplained ischemic events, unusual radiographic findings, or signs of systemic inflammation. A multidisciplinary approach can be used among rheumatologists, vascular cardiologists, radiologists, and vascular interventionalists to raise diagnostic certainty in cases with large- and/or medium-vessel involvement. Recognition of cardiac manifestations, including myocarditis seen in forms of small-vessel vasculitis (eg, eosinophilic granulomatosis with polyangiitis) or coronary arteritis seen in forms of medium-vessel vasculitis (eg, polyarteritis nodosa and Kawasaki disease) is important owing to the associated mortality. Clinical phenotype, radiographic features, laboratory tests, and histology can help to differentiate vasculitis from noninflammatory vasculopathies and define the etiology of the vasculitis to help guide appropriate treatment. Various modalities of imaging can give clues to aid in diagnosis of vasculitis and can be considered in the context of physician preference and patient comorbidity. While conventional angiography can give important details regarding luminal anatomy and pressure gradients in medium- and large-vessel vasculitis, noninvasive imaging modalities such as computed tomographic angiography, magnetic resonance angiography, color Doppler ultrasound, and positron emission tomography/computed tomography are commonly used for both diagnosis and follow-up. Treatment for systemic vasculitis should be coordinated with an experienced rheumatologist., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists., Methods: Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel., Results: We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted., Conclusion: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD., (© 2022 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: Kawasaki disease (KD) is a self-limited vasculitis affecting medium-sized vessels with a predilection for the coronary arteries. Although treatment reduces the likelihood of developing of coronary artery aneurysms, 5% of patients still develop aneurysms despite treatment, making KD the leading cause of acquired heart disease in children in the United States. Consequently, there is a great deal of interest in optimizing treatment regimens, particularly for higher-risk patients, to decrease morbidity. The aim of this systematic review is to support the development of the American College of Rheumatology/Vasculitis Foundation for the diagnosis and management of KD, focusing on the more complex scenarios in which rheumatologists may become involved, such as high-risk and refractory disease., Methods: Eighty-nine articles were considered for full review in this systematic literature review to address 16 Population, Intervention, Comparison, and Outcome questions related to KD. Data were abstracted in hierarchical fashion. Randomized control trials (RCTs) were considered first; if none were identified or if they contained insufficient information, comparative observational studies were then viewed, followed by single-arm observational studies/single arms from comparative studies. Only observational studies with more than 10 subjects with vasculitis were included., Results: Eight RCTs and 28 observational studies that addressed the questions were identified. Two questions were addressed by RCTs, seven questions had at least some comparative observational studies, three questions were only addressed by single-arm data, and four questions had no relevant studies., Conclusion: This systematic review evaluates the benefits and harms of treatments for KD beyond first-line therapy., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN)., Methods: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel., Results: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted., Conclusion: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN., (© 2021 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)., Methods: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel., Results: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations., Conclusion: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases., (© 2021, American College of Rheumatology.)

Objective: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis., Methods: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel., Results: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions., Conclusion: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions., (© 2021 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

This systematic review compares treatment options for patients with giant cell arteritis (GCA) and evaluates the test accuracy of studies used in diagnosing and monitoring GCA. These studies were used to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) vasculitis management guidelines. A systematic review and search of articles in English in Ovid Medline, PubMed, Embase, and the Cochrane Library was conducted. Articles were screened for suitability, and studies presenting the highest level of evidence were given preference. Three hundred ninety-nine full-text articles addressing GCA questions were reviewed to inform 27 Population, Intervention, Comparison, and Outcome questions. No benefit was found with intravenous glucocorticoids (GCs) compared with high-dose oral GCs in patients with cranial ischemic symptoms (27.4% vs 12.3%; odds ratio [OR] 2.39 [95% confidence interval (CI) 0.75-7.62], [very low certainty of evidence]). Weekly tocilizumab with a 26-week GC taper was superior to a 52-week GC taper in patients achieving remission (risk ratio 4.00 [95% CI 1.97-8.12], [low certainty of evidence]). Non-GC immunosuppressive therapies with GCs compared with GCs alone showed no statistically significant in relapse at 1 year (OR 0.87 [95% CI 0.73-1.04], [moderate certainty of evidence]) or serious adverse events (OR 0.81 [95% CI 0.54-1.20]; [moderate certainty of evidence]). Temporal artery biopsy has a sensitivity of 61% (95% CI 38%-79%) and a specificity of 98% (95% CI 95%-99%) in patients with a clinical diagnosis of suspected GCA. This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the diagnosis and monitoring of GCA., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN)., Methods: A systematic search of published English-language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference., Results: Of 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high-dose glucocorticoids (GCs) is effective as an induction treatment for newly diagnosed active and severe PAN. GC monotherapy is adequate in the majority of patients with nonsevere PAN, although it has a high relapse rate with GC taper. There was insufficient data in determining the optimal duration of non-GC and GC maintenance therapy. Tumor necrosis factor inhibitors are effective treatment for patients with deficiency of adenosine deaminase 2 (DADA2) with stroke and vasculitis manifestations., Conclusion: This comprehensive systematic review synthesizes and evaluates the harms and benefits of different treatment options and the accuracy of commonly used tests for the diagnosis of systemic PAN. Data for diagnosis and management of PAN and DADA2 are mostly limited to observational studies. More high-quality RCTs are needed., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Takayasu's arteritis (TAK) is a granulomatous large-vessel vasculitis primarily affecting the aorta and its proximal branches. TAK can be a difficult disease to diagnose and manage given the rarity of the disease as well as current limitations in biomarkers, imperfect imaging modalities, and few randomized controlled trials., Methods: In developing the American College of Rheumatology/Vasculitis Foundation guideline for the management of TAK, we performed an extensive systematic literature review to guide our recommendations. We included RCTs first. When RCTs were not available, we included observational studies that reported on patient-important outcomes for the intervention and comparison. When studies with comparative data were not available, we included case series that present patient-important outcomes for either the intervention or the comparison., Results: Three hundred forty-seven articles were included for full review to answer 27 population, intervention, comparison, and outcome questions related to TAK. Ten studies were evaluated that addressed the use of glucocorticoids (GCs), non-GC nonbiologic therapies, as well as biologics in treating TAK. A total of 33 studies, including 8 comparative studies, were included to determine the test accuracy of commonly available diagnostic tests for TAK., Conclusion: This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the management of TAK., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Vasculitis can be a life-threatening complication associated with high mortality and morbidity among patients with primary immunodeficiencies (PIDs), including variants of severe and combined immunodeficiencies ((S)CID). Our understanding of vasculitis in partial defects in recombination activating gene (RAG) deficiency, a prototype of (S)CIDs, is limited with no published systematic evaluation of diagnostic and therapeutic modalities. In this report, we sought to establish the clinical, laboratory features, and treatment outcome of patients with vasculitis due to partial RAG deficiency. Vasculitis was a major complication in eight (13%) of 62 patients in our cohort with partial RAG deficiency with features of infections and immune dysregulation. Vasculitis occurred early in life, often as first sign of disease (50%) and was complicated by significant end organ damage. Viral infections often preceded the onset of predominately non-granulomatous-small vessel vasculitis. Autoantibodies against cytokines (IFN-α, -ω, and IL-12) were detected in a large fraction of the cases tested (80%), whereas the majority of patients were anti-neutrophil cytoplasmic antibodies (ANCA) negative (>80%). Genetic diagnosis of RAG deficiency was delayed up to 2 years from the onset of vasculitis. Clinical cases with sole skin manifestation responded well to first-line steroid treatment, whereas systemic vasculitis with severe end-organ complications required second-line immunosuppression and/or hematopoietic stem cell transplantation (HSCT) for definitive management. In conclusion, our data suggest that vasculitis in partial RAG deficiency is prevalent among patients with partial RAG deficiency and is associated with high morbidity. Therefore, partial RAG deficiency should be included in the differential diagnosis of patients with early-onset systemic vasculitis. Diagnostic serology may be misleading with ANCA negative findings, and search for conventional autoantibodies should be extended to include those targeting cytokines., (Copyright © 2020 Geier, Farmer, Foldvari, Ujhazi, Steininger, Sleasman, Parikh, Dilley, Pai, Henderson, Hazen, Neven, Moshous, Sharapova, Mihailova, Yankova, Naumova, Özen, Byram, Fernandez, Wolf, Eibl, Notarangelo, Calabrese and Walter.)

Purpose of Review: The goal of this review is to provide an up-to-date approach to diagnosis and management of patients with central nervous system (CNS) vasculitis., Recent Findings: Challenges in diagnosis of CNS vasculitis still exist due to the broad differential diagnosis and generally nonspecific initial clinical manifestations. Differentiation between primary angiitis of the CNS (PACNS) and secondary causes is important in guiding management. Recent longitudinal cohort studies have improved our understanding of PACNS. Advances in neuroimaging and molecular testing have enhanced diagnostic decision-making. Therapy remains largely empiric, guided by observational data. Despite the limited use of targeted therapies, glucocorticoids and cyclophosphamide remain the mainstays of therapy in PACNS. Securing a diagnosis through a careful, team-based approach with emphasis on ruling out possible mimics is paramount in the management of patients with CNS vasculitis.

Purpose: The aim of this study was to develop and validate case-finding algorithms for granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (Churg-Strauss, EGPA)., Methods: Two hundred fifty patients per disease were randomly selected from two large healthcare systems using the International Classification of Diseases version 9 (ICD9) codes for GPA/EGPA (446.4) and MPA (446.0). Sixteen case-finding algorithms were constructed using a combination of ICD9 code, encounter type (inpatient or outpatient), physician specialty, use of immunosuppressive medications, and the anti-neutrophil cytoplasmic antibody type. Algorithms with the highest average positive predictive value (PPV) were validated in a third healthcare system., Results: An algorithm excluding patients with eosinophilia or asthma and including the encounter type and physician specialty had the highest PPV for GPA (92.4%). An algorithm including patients with eosinophilia and asthma and the physician specialty had the highest PPV for EGPA (100%). An algorithm including patients with one of the diagnoses (alveolar hemorrhage, interstitial lung disease, glomerulonephritis, and acute or chronic kidney disease), encounter type, physician specialty, and immunosuppressive medications had the highest PPV for MPA (76.2%). When validated in a third healthcare system, these algorithms had high PPV (85.9% for GPA, 85.7% for EGPA, and 61.5% for MPA). Adding the anti-neutrophil cytoplasmic antibody type increased the PPV to 94.4%, 100%, and 81.2% for GPA, EGPA, and MPA, respectively., Conclusion: Case-finding algorithms accurately identify patients with GPA, EGPA, and MPA in administrative databases. These algorithms can be used to assemble population-based cohorts and facilitate future research in epidemiology, drug safety, and comparative effectiveness. Copyright © 2016 John Wiley & Sons, Ltd., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright © 2016 John Wiley & Sons, Ltd.)

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Premature termination codons represent a common minority of CFTR mutations, and are caused by base pair substitutions that produce abnormal stop codons in the coding sequence. Select aminoglycosides induce "translational readthrough" of premature stop codons and have been shown to restore full-length functional protein in a number of preclinical and clinical settings. We studied two well-described premature termination codons found in the distal open reading frame of CFTR, W1282X and R1162X, expressed in polarizing and nonpolarizing cells. Our findings indicate that W1282X CFTR-expressing cells demonstrate significantly greater CFTR activity when overexpressed compared with R1162X CFTR cells, even when truncated protein is the predominant form. In addition, our results show that the combination of stimulated expression and stop codon suppression produces additive effects on CFTR-mediated ion transport. These findings provide evidence that W1282X CFTR exhibits membrane localization and retained chloride channel function after enhanced expression, and suggest that patients harboring this mutation may be more susceptible to CFTR rescue.

An experimental study was conducted in two PACUs to test the effect of two warming methods on core and surface temperatures, oxygen hemoglobin saturation, blood pressure, and perceived comfort of hypothermic postanesthesia patients. The study was based by Selye's theory of stress, which states that when individuals are confronted with stressors, physiological adaptation occurs to maintain homeostasis. Subjects studied were 91 adult patients who were randomly assigned to two groups: group 1 patients were warmed with the Bair Hugger Warming System (Augustine Medical, Inc, Eden Prairie, MN), and group 2 patients were warmed with warmed bath blankets. Multiple analysis of variance with repeated measures demonstrated significant differences between the two groups on surface temperature, oxygen hemoglobin saturation, and perceived comfort. No significant differences were found between the two groups on core temperature and blood pressure. Implications for PACU nurses include an efficient, cost-saving method to promote patient adaptation to the stressors of inadvertent hypothermia. Further studies are needed to validate the findings from this study and to test nurses' responses to the Bair Hugger Warming System.