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ABSTRACTIntroductionGiant Cell Arteritis (GCA) is the most common systemic vasculitis worldwide. For decades, glucocorticoids have represented the mainstay of treatment, at the expense of toxic systemic effects owing to prolonged courses of high-dose treatment regimens. The search for effective drugs permitting lower glucocorticoid treatment regimens in GCA has been afrustrating one. The recent successful therapeutic application of tocilizumab, an interleukin-6 receptor inhibitor, has transformed the treatment of GCA and catalyzed research exploring other promising therapeutic targets.Areas coveredThis review explores emerging drugs in preclinical and clinical development for the management of GCA, in addition to synthesizing data on the current standard of care therapeutic agents. Drug therapies were identified by search of MEDLINE and PubMed in addition to trials from registries (clinicaltrials.gov, clinicaltrialsregister.eu, pubmed.gov) from theyear 2010.Expert opinionTocilizumab has revolutionized the treatment of GCA. However, much remains to be learned about its optimal usage in GCA and asubstantial minority of patients do not achieve sustained glucocorticoid-free remission. Numerous exciting new agents are under investigation to fill this treatment gap in GCA, with the GM-CSF inhibitor mavrilimumab, and IL-12/23 blockade with ustekinumab providing promise through targeting the GCA pathogenic pathway in its proximal portion.

Purpose: The primary goal of this study was to establish a normative data set representing intraoral time series swallow pressure profiles for healthy adults using a novel wearable intraoral pressure sensing system, OroPress, developed to help with dysphagia (swallow disorder) clinical screening. Methods: Swallow intraoral pressure-time profiles for 35 healthy adults (17 male, 18 female) swallowing water (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3 \times 5\, {\text{cm}^3}$$\end{document}; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3 \times 10\, {\text{cm}^3}$$\end{document}) and custard (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3 \times 5\, {\text{cm}^3}$$\end{document}) boluses ($N=9\times 35=315$\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N=9 \times 35 = 315$$\end{document}) were recorded using OroPress. Results: General swallow profile traits are identified to characterise an effective, efficient swallow. A profile-specific swallow envelope function is devised which in combination with profile metrics, provides a simple means of categorizing swallows as effective or impaired. Conclusion: The swallow profile data trace with superimposed and colour coded peaks, envelope function and related swallow metrics provides a simple human readable graphic to aid the real-time instrumented identification of subjects warranting more in-depth clinical assessment. It may also prove useful in the selection of training set profiles for machine learning and other analysis tools which could improve the discriminatory capabilities of intraoral pressure measurement in dysphagia diagnostics.

Objective: To establish if there is a difference in health-related quality of life and vision-related quality of life in patients with a confirmed diagnosis of giant cell arteritis compared with those with clinical features suspicious for the disease at initial presentation but in whom giant cell arteritis is ultimately excluded.Methods: A cross-sectional study of 116 patients who presented to two tertiary referral hospitals in Ireland with symptoms suspicious for giant cell arteritis was performed between August 2011 and June 2017. The Vision Core Measurement 1 and Short Form-36 questionnaires were used as assessment tools.Results: The mean (standard deviation) age of all 116 participants was 69.4 (9.3) years of whom 74 (63.8%) were female. In the giant cell arteritis group, 19.7% had permanent loss of vision and 54.7% had non-permanent visual disturbance. Vision Core Measurement 1 score in the giant cell arteritis group correlated with worse eye visual acuity (r = 0.4233, p = 0.0002). The Short Form-36 subscales of role physical (p = 0.0002), role emotional (p = 0.024), and the mental composite score (p = 0.012) were significantly worse in patients with giant cell arteritis. A significant correlation was found between vision-related quality of life scores and all Short Form-36 subscale scores except bodily pain (r = −0.215 to −0.399, p < 0.05 for all), and between social functioning and visual acuity in the better eye (r = −0.242, p = 0.038).Conclusion: Vision-related quality of life is an important subjective concern for both patients presenting with a suspicion of giant cell arteritis and those with a definite diagnosis of giant cell arteritis. Features of giant cell arteritis impact on patients’ physical and emotional states and vision influences global quality of life in giant cell arteritis. A long-term multidisciplinary approach is warranted for clinical, physical, and psychological treatment and support.

Objective.To identify shared and distinct features of giant cell arteritis (GCA) and coronavirus disease 2019(COVID-19) to reduce diagnostic errors that could cause delays in correct treatment.Methods.Two systematic literature reviews determined the frequency of clinical features of GCA and COVID-19 in published reports. Frequencies in each disease were summarized using medians and ranges.Results.Headache was common in GCA but was also observed in COVID-19 (GCA 66%, COVID-19 10%). Jaw claudication or visual loss (43% and 26% in GCA, respectively) generally were not reported in COVID-19. Both diseases featured fatigue (GCA 38%, COVID-19 43%) and elevated inflammatory markers (C-reactive protein [CRP] elevated in 100% of GCA, 66% of COVID-19), but platelet count was elevated in 47% of GCA but only 4% of COVID-19 cases. Cough and fever were commonly reported in COVID-19 and less frequently in GCA (cough, 63% for COVID-19 vs 12% for GCA; fever, 83% for COVID-19 vs 27% for GCA). Gastrointestinal upset was occasionally reported in COVID-19 (8%), rarely in GCA (4%). Lymphopenia was more common in COVID-19 than GCA (53% in COVID-19, 2% in GCA). Alteration of smell and taste have been described in GCA but their frequency is unclear.Conclusion.Overlapping features of GCA and COVID-19 include headache, fever, elevated CRP and cough. Jaw claudication, visual loss, platelet count and lymphocyte count may be more discriminatory. Physicians should be aware of the possibility of diagnostic confusion. We have designed a simple checklist to aid evidence-based evaluation of patients with suspected GCA.

Objective.To evaluate the relative risk (RR) of pulmonary disease among patients with rheumatoid arthritis (RA) treated with leflunomide (LEF).Methods.We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to April 15, 2014. We included double-blind randomized controlled trials (RCT) of LEF versus placebo or active comparator agents in adults with RA. Studies with fewer than 50 subjects or shorter than 12 weeks were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. We compared RR differences using the Mantel-Haenszel random-effects method to assess total respiratory adverse events, infectious respiratory adverse events, noninfectious respiratory adverse events, interstitial lung disease, and death.Results.Our literature search returned 5673 results. A total of 8 studies, 4 with placebo comparators, met our inclusion criteria. There were 708 respiratory adverse events documented in 4579 participants. Six cases of pneumonitis occurred, all in the comparator group. Four pulmonary deaths were reported, none in the LEF group. LEF was not associated with an increased risk of total adverse respiratory events (RR 0.99, 95% CI 0.56–1.78) or infectious respiratory adverse events (RR 1.02, 95% CI 0.58–1.82). LEF was associated with a decreased risk of noninfectious respiratory adverse events (RR 0.64, 95% CI 0.41–0.97).Conclusion.Our study found no evidence of increased respiratory adverse events in RCT of LEF treatment.

Objective.Increased body mass index (BMI) in patients with ankylosing spondylitis (AS) is associated with a greater burden of symptoms and poor perceptions of the benefits of exercise. In AS, the effect of obesity on disease characteristics and exercise perceptions is unknown. We evaluated the prevalence of obesity in AS, to assess the attitudes of patients toward exercise and to evaluate the effect of obesity on symptoms and disease activity.Methods.Demographic data and disease characteristics were collected from 46 patients with AS. Disease activity, symptomatology, and functional disability were examined using standard AS questionnaires. BMI was calculated. Comorbidity was analyzed using the Charlson Comorbidity Index. Patients’ attitudes toward exercise were assessed using the Exercise Benefits and Barriers Scale (EBBS). We compared the disease characteristics, perceptions regarding exercise, and functional limitations in those who were overweight to those who had a normal BMI.Results.The mean BMI in the group was 27.4; 67.5% of subjects were overweight or obese. There was a statistically significant difference between those who were overweight and those with a normal BMI regarding their perceptions of exercise (EBBS 124.7 vs 136.6, respectively), functional limitation (Bath AS Functional Index 4.7 vs 2.5, Health Assessment Questionnaire 0.88 vs 0.26), and disease activity (Bath AS Disease Activity Index 4.8 vs 2.9). There was no difference between the groups in terms of their comorbid conditions or other demographic variables.Conclusion.The majority of patients in this AS cohort were overweight. They had a greater burden of symptoms, worse perceptions regarding the benefits of exercise, and enhanced awareness of their barriers to exercising. This is of particular concern in a disease where exercise plays a crucial role.

The criteria used for calling emergency response teams to patients at-risk of clinical deterioration in the acute care adult hospital population include the criterion ‘patient of concern’. When calling teams to patients of concern, some ‘changes of concern’ used by nurses have been identified; however the validity of these ‘changes of concern’ is unknown.

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A sequence of tasks that must be performed on a sequential database can be scheduled in various ways. Schedules will differ with respect to the number of accesses made to peripheral storage devices and the amount of memory space consumed by buffers. Buffer requirements are discussed for task schedules that avoid accesses to peripherals storing the sequential database. The relationship between certain thrifty scheduling policies and loop jamming, a standard code optimization technique, is also identified. Application to UNIX pipelines and to file processing is discussed.

The activity of soluble protein kinase and phosphorylation of endogenous synaptosomal proteins were studied in vitro, in the hippocampus and cerebral cortex of rats 3, 12, or 24 months of age. No between‐age differences in the activity of cyclic AMP‐dependent or independent protein kinase were detected in either brain region. The degree of stimulation by cyclic AMP and the apparent Ka, for cyclic AMP were similar at all stages. Cyclic AMP stimulated the phosphorylation of synaptosomal proteins from the cerebral cortex, hippocampus, caudate nucleus, and cerebellum of rats at all ages. There were no significant differences across age in the extent of phosphorylation of any membrane proteins in any brain region. The number and staining density of synaptosornal proteins separated by polyacrylamide gel electrophoresis were also similar at all ages. These studies indicate that the cyclic AMP‐dependent phosphorylation system in the rat brain does not change during advanced aging.

Conclusion Unfortunately, we do not know how closely WPSM simulates the regional impact process, since we cannot observe the economy's “true” multipliers. Nor are we on sound empirical grounds for concluding that WPSM's simulation properties are necessarily superior to those of other state models, such as the static input-output formulation.

Originally built in 1977, the Washington Projection and Simulation Model (WPSM) is a regional interindustry econometric model designed for forecasting and impact analysis. This article describes the most recent formulation of WPSM, analyzes the accuracy of the long-range forecasts prepared with the original model in 1976, and evaluates the model's simulation properties. The experience of developing and applying WPSM over the past ten years provides a basis for assessing the relative merits of this seldomly followed approach to regional economic modeling.

A blanket policy against publishing technical papers is as much a mistake as a policy of approving virtually all potential papers for publication. Companies adopting either extreme may be costing themselves money. Accordingly, management must evaluate the merits of each technical paper. Publishing a particular article may enhance a company's stature, but care should be exercised so as not to jeopardize patent position — particularly outside the United States. Guidelines are offered to help management decide between the benefits and the deterrents to publication.

Giant cell arteritis (GCA) is the most common form of systemic vasculitis. It is a potentially severe disease with 25% of patients suffering vision loss or stroke. Our treatment paradigm is based on glucocorticoids. Glucocorticoids are required in high doses for prolonged periods and subsequently are associated with a significant amount of treatment-related morbidity. Alternative treatment options are urgently needed to minimize these glucocorticoid adverse events. Many other agents, such as methotrexate and tumour necrosis factor alpha inhibitors have been used in GCA, with limited or no evidence of benefit. Our emerging understanding of the pathogenic processes involved in GCA has led to an increased interest in the use of biologic agents to treat the disease. Two randomized controlled trials have recently reported dramatic effects of the use of the interleukin-6 targeted biologic tocilizumab in GCA, with significant increases in remission rates and decreases in glucocorticoid burden. While encouraging, longer-term and additional outcomes are awaited to clarify the exact positioning of tocilizumab in the treatment approach. Emerging data for other biologic agents, particularly abatacept and ustekinumab, are also encouraging but less well advanced. We are at the dawn of a new era in GCA treatment, but uncertainties and opportunities abound.