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1. Headache/migraine-related stigma, quality of life, disability, and most bothersome symptom in adults with current versus previous high-frequency headache/migraine and medication overuse: results of the Migraine Report Card survey

Author

Dawn C. Buse, Roger Cady, Amaal J. Starling, Meghan Buzby, Charlie Spinale, Kathy Steinberg, Kevin Lenaburg, and Steven Kymes

Subjects
Chronic migraine, Patient perspective, Disease stigma, Medication overuse, High-frequency migraine, Harris Poll, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background High-frequency headache/migraine (HFM) and overuse of acute medication (medication overuse [MO]) are associated with increased disability and impact. Experiencing both HFM and MO can potentially compound impacts, including stigma; however, evidence of this is limited. The objective of this report was to evaluate self-reported stigma, health-related quality of life (HRQoL), disability, and migraine symptomology in US adults with HFM + MO from the Harris Poll Migraine Report Card survey. Methods US adults (≥ 18 yrs., no upper age limit) who screened positive for migraine per the ID Migraine™ screener completed an online survey. Participants were classified into “current HFM + MO” (≥ 8 days/month with headache/migraine and ≥ 10 days/month of acute medication use over last few months) or “previous HFM + MO” (previously experienced HFM + MO, headaches now occur ≤ 7 days/month with ≤ 9 days/month of acute medication use). Stigma, HRQoL, disability, and most bothersome symptom (MBS) were captured. The validated 8-item Stigma Scale for Chronic Illnesses (SSCI-8) assessed internal and external stigma (scores ≥ 60 are clinically significant). Raw data were weighted to the US adult population. Statistically significant differences were determined by a standard t-test of column proportions and means at the 90% (p

Published
2024
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2. Harris Poll Migraine Report Card: population-based examination of high-frequency headache/migraine and acute medication overuse

Author

Amaal J. Starling, Roger Cady, Dawn C. Buse, Meghan Buzby, Charlie Spinale, Kathy Steinberg, Kevin Lenaburg, and Steven Kymes

Subjects
Acute medication overuse, High-frequency migraine, Chronic migraine, Patient perspective, Harris Poll, Survey, Medicine
Abstract

Abstract Background Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use. Methods An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into “current HFM+AMO” (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n=440) or “previous HFM+AMO” (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n=110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. Results Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P>0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health (P0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions (P>0.1 for current vs previous). Conclusion Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden. Graphical Abstract

Published
2024
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3. Long-term effectiveness of eptinezumab in patients with migraine and prior preventive treatment failures: extension of a randomized controlled trial

Author

Messoud Ashina, Stewart J. Tepper, Astrid Gendolla, Bjørn Sperling, Anders Ettrup, Mette Krog Josiassen, and Amaal J. Starling

Subjects
Efficacy, Most bothersome symptom, Quality of life, Work productivity, Medicine
Abstract

Abstract Background Eptinezumab demonstrated efficacy in adults with migraine and prior preventive treatment failures in the placebo-controlled phase of the DELIVER clinical trial; its long-term effectiveness in this population has not yet been reported. The objective of this study was to evaluate the long-term effectiveness of eptinezumab in a migraine patient population during the 48-week extension phase of DELIVER. Methods DELIVER was conducted June 1, 2020 to September 15, 2022. 865 adults with migraine, with documented evidence of 2–4 prior preventive migraine treatment failures and with completion of the 24-week placebo-controlled period of DELIVER received eptinezumab (100 or 300 mg) during the dose-blinded extension, either continuing their randomized dose or, if originally receiving placebo, were randomized 1:1 to an eptinezumab dose (100 or 300 mg). A mixed model for repeated measures was used to evaluate changes from baseline in the number of monthly migraine days (MMDs). Results Of 865 patients entering the extension (eptinezumab 100 mg, n = 433; 300 mg, n = 432), 782 (90.4%) completed and 11 (1.3%) discontinued due to an adverse event. Eptinezumab was associated with early and sustained reductions in migraine frequency. Mean MMDs at baseline were approximately 14 days across groups. Mean (standard error) change from baseline in MMDs over the final dosing interval (weeks 61–72) was −6.4 (0.50) with placebo/eptinezumab 100 mg, –7.3 (0.49) with placebo/eptinezumab 300 mg, –7.1 (0.39) with eptinezumab 100 mg, and −7.0 (0.39) with eptinezumab 300 mg. During weeks 61–72, 63–70% of patients demonstrated ≥ 50% reduction in MMDs, and 36–45% demonstrated ≥ 75% reduction. Headache severity and acute medication use reductions, and patient-reported improvements in most bothersome symptom, disease status, quality of life, and work productivity, were observed. Adverse events were generally mild, transient, and similar in frequency/type to previous eptinezumab trials. Conclusions The long-term effectiveness and safety/tolerability of eptinezumab in patients with migraine and 2–4 prior preventive treatment failures was demonstrated by high completion rates and migraine-preventive benefits sustained for up to 18 months, implying that eptinezumab is a viable long-term treatment option for patients still seeking successful migraine treatments. Trial registration ClinicalTrials.gov (Identifier: NCT04418765; URL: https://www.clinicaltrials.gov/ct2/show/NCT04418765 ); EudraCT (Identifier: 2019-004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 ). Graphical Abstract

Published
2023
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4. Baseline Normative and Test–Retest Reliability Data for Sideline Concussion Assessment Measures in Youth

Author

Jennifer V. Wethe, Jamie Bogle, David W. Dodick, Marci D. Howard, Amanda Rach Gould, Richard J. Butterfield, Matthew R. Buras, Jennifer Adler, Alexandra Talaber, David Soma, and Amaal J. Starling

Subjects
child, adolescent, athletes, brain concussion, reproducibility of results, Medicine (General), R5-920
Abstract

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King–Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test–retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test–retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = −0.309 to 0.651). Commonly used measures of concussion vary regarding test–retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Published
2024
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5. Early clinical experience with eptinezumab: results of a retrospective observational study of patient response in the United States

Author

Amaal J. Starling, Steven Kymes, Divya Asher, Seema Soni-Brahmbhatt, and Meghana Karnik-Henry

Subjects
Eptinezumab, Headache, Migraine, Monoclonal antibody, Preventive treatment, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The efficacy and safety of eptinezumab for preventive migraine treatment in adults have been demonstrated in multiple, large-scale clinical trials. This non-interventional, retrospective, observational chart review was conducted to examine patient response to eptinezumab 100 mg or 300 mg every 12 weeks for 6 months in the clinical setting. Methods Eight headache specialists who reported early clinical experience with eptinezumab enrolled the first adults (1–6 adults per clinician; age ≥ 18 years) who met predefined selection criteria (including ≥ 12-month history of migraine, ≥ 4 migraine days/month prior to eptinezumab initiation, receipt of ≥ 2 consecutive eptinezumab doses, and ≥ 12-week follow-up period), and provided detailed patient, disease, treatment, and outcome information via SurveyMonkey and standardized case-report forms. Results Charts from 31 adults (median age, 49 years) with migraine (93.6% chronic) who received eptinezumab for the preventive treatment of migraine were reviewed. Most patients (26/31 [83.9%]) were initiated at 100 mg. Eptinezumab reduced mean headache frequency (24.3 monthly headache days [MHDs] at baseline; 17.1 MHDs at Month 6); mean migraine frequency (17.3 monthly migraine days [MMDs] at baseline; 9.1 MMDs at Month 6); attack severity (17/31 [54.8%] patients); acute headache medication use (12.5 acute medication days at baseline; 7.4 at Month 6); and patient-reported disability (11/22 [50.0%] severe at baseline; 7/19 [36.8%] at Month 6). More than three-quarters of patients (24/31 [77.4%]) perceived improved disability/function and most (30/31 [96.8%]) perceived eptinezumab to be well tolerated after 6 months. Most of the headache specialists reported that eptinezumab was well tolerated by patients (30/31 [96.8%]) and that the intravenous infusion experience was not challenging. Conclusions Patients with migraine who received 6 months of preventive treatment with eptinezumab experienced reductions in migraine and headache frequency, disability, and acute medication use during the course of treatment.

Published
2023
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6. Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study

Author

Robert P. Cowan, Michael J. Marmura, Hans-Christoph Diener, Amaal J. Starling, Jack Schim, Joe Hirman, Thomas Brevig, and Roger Cady

Subjects
Chronic migraine, Eptinezumab, Medication-overuse headache, Serotonin 5-HT1 receptor agonists, Analgesics, Medicine
Abstract

Abstract Background Patients with chronic migraine (CM) treated with eptinezumab in the PROMISE-2 trial achieved greater reductions in migraine and headache frequency, impact, and acute headache medication (AHM) use than did patients who received placebo. This post hoc analysis examines relationships between headache frequency reductions and changes in AHM use in patients in PROMISE-2. Methods PROMISE-2 was a double-blind, placebo-controlled trial conducted in adults with CM. Patients were randomized to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously once every 12 weeks for up to two doses. Patients recorded headache/AHM information daily and for each event in an electronic diary; data from all days with daily reports were included. Shifts in headache frequency and AHM use were assessed in the three populations: total CM population, patients with CM and medication-overuse headache (MOH), and patients with CM and MOH who were ≥ 50% responders during treatment (response over weeks 1–24). Results A total of 1072 adults with CM received treatment (eptinezumab, n = 706; placebo, n = 366). Mean baseline headache frequency was 20.5 days; mean baseline AHM days was 13.4; 431 patients had MOH, of which 225 (52.2%) experienced ≥50% response over weeks 1–24. Relative to baseline, the proportion of days with both headache and AHM use decreased 25.1% (eptinezumab) versus 17.0% (placebo) in the total population (N = 1072), 29.2% versus 18.4% in the MOH subpopulation (n = 431), and 38.3% versus 31.5% in the CM with MOH population with ≥50% response subgroup (n = 225) during weeks 1–24. The proportion of days with headache and triptan use decreased 9.1% (eptinezumab) versus 5.8% (placebo), 11.8% versus 7.2%, and 14.5% versus 12.6%, respectively. Reductions in other AHM types were smaller. Conclusions In this post hoc analysis, eptinezumab use in patients with CM was associated with greater decreases in days with headache with AHM overall and with triptans in particular. The magnitude of effect was greater in the subgroup of CM patients with MOH and ≥ 50% response. Trial registration ClinicalTrials.gov Identifier: NCT02974153 . Graphical abstract Eptinezumab reduces headache frequency and acute medication use in patients with chronic migraine.

Published
2022
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7. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Author

Deena E. Kuruvilla, Joseph I. Mann, Stewart J. Tepper, Amaal J. Starling, Gregory Panza, and Michael A. L. Johnson

Subjects
Medicine, Science
Abstract

Abstract Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2–8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting. Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904 .

Published
2022
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8. Development of a Boston-area 50-km fiber quantum network testbed.

Author

Eric Bersin, Matthew Grein, Madison Sutula, Ryan Murphy, Yan Qi Huan, Mark Stevens, Aziza Suleymanzade, Catherine Lee 0001, Ralf Riedinger, David J. Starling, Pieter-Jan Stas, Can M. Knaut, Neil Sinclair, Daniel R. Assumpcao, Yan-Cheng Wei, Erik N. Knall, Bartholomeus Machielse, Denis D. Sukachev, David S. Levonian, Mihir K. Bhaskar, Marko Loncar, Scott Hamilton, Mikhail Lukin, Dirk R. Englund, and P. Benjamin Dixon

Published
2023
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9. Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials

Author

Robert E. Shapiro, Helen M. Hochstetler, Ellen B. Dennehy, Rashna Khanna, Erin Gautier Doty, Paul H. Berg, and Amaal J. Starling

Subjects
Migraine, Cardiovascular disease, Lasmiditan, Safety, Ditan, Medicine
Abstract

Abstract Background In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs. Methods SAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200 mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects. Results In this pooled analysis, a total of 4439 patients received ≥1 dose of study drug. A total of 3500 patients (78.8%) had ≥1 CVRF, and 1833 patients (41.3%) had ≥2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2 h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ≥1, ≥ 2, ≥ 3, or ≥ 4 CVRFs was palpitations. Conclusions When analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety. Trial registration ClinicalTrials.gov NCT02439320 (SAMURAI), registered 18 March 2015 and ClinicalTrials.gov NCT02605174 (SPARTAN), registered 11 November 2015.

Published
2019
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12. Compressive sensing for spatial and spectral flame diagnostics

Author

David J. Starling and Joseph Ranalli

Subjects
Medicine, Science
Abstract

Abstract Combustion research requires the use of state of the art diagnostic tools, including high energy lasers and gated, cooled CCDs. However, these tools may present a cost barrier for laboratories with limited resources. While the cost of high energy lasers and low-noise cameras continues to decline, new imaging technologies are being developed to address both cost and complexity. In this paper, we analyze the use of compressive sensing for flame diagnostics by reconstructing Raman images and calculating mole fractions as a function of radial depth for a highly strained, N2-H2 diffusion flame. We find good agreement with previous results, and discuss the benefits and drawbacks of this technique.

Published
2018
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19. Data from Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Author

Xiang S. Ye, Yong Wang, Juan A. Velasco, Courtney Tate, James J. Starling, Louis F. Stancato, Chuan Shih, Susan E. Pratt, Stephen H. Parsons, Songqing Na, Denis McCann, Mary Mader, Enrique Jambrina, Jeremy R. Graff, Raymond Gilmour, Alfonso De Dios, Edward M. Chan, Harold B. Brooks, Nathan A. Brooks, Bryan D. Anderson, and Robert M. Campbell

Abstract

p38α mitogen-activated protein kinase (MAPK) is activated in cancer cells in response to environmental factors, oncogenic stress, radiation, and chemotherapy. p38α MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2), and regulates the production of cytokines in the tumor microenvironment, such as TNF-α, interleukin-1β (IL-1β), IL-6, and CXCL8 (IL-8). p38α MAPK is highly expressed in human cancers and may play a role in tumor growth, invasion, metastasis, and drug resistance. LY2228820 dimesylate (hereafter LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 MAPK in vitro (IC50 = 5.3 and 3.2 nmol/L, respectively). In cell-based assays, LY2228820 potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC50 = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L. LY2228820 also reduced TNF-α secretion by lipopolysaccharide/IFN-γ–stimulated macrophages (IC50 = 6.3 nmol/L). In mice transplanted with B16-F10 melanoma, tumor phospho-MK2 (p-MK2) was inhibited by LY2228820 in a dose-dependent manner [threshold effective dose (TED)70 = 11.2 mg/kg]. Significant target inhibition (>40% reduction in p-MK2) was maintained for 4 to 8 hours following a single 10 mg/kg oral dose. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non–small cell lung cancer, ovarian, glioma, myeloma, breast). In summary, LY2228820 is a p38 MAPK inhibitor, which has been optimized for potency, selectivity, drug-like properties (such as oral bioavailability), and efficacy in animal models of human cancer. Mol Cancer Ther; 13(2); 364–74. ©2013 AACR.

Published
2023
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22. Supplementary Figure 1 from Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Author

Xiang S. Ye, Yong Wang, Juan A. Velasco, Courtney Tate, James J. Starling, Louis F. Stancato, Chuan Shih, Susan E. Pratt, Stephen H. Parsons, Songqing Na, Denis McCann, Mary Mader, Enrique Jambrina, Jeremy R. Graff, Raymond Gilmour, Alfonso De Dios, Edward M. Chan, Harold B. Brooks, Nathan A. Brooks, Bryan D. Anderson, and Robert M. Campbell

Abstract

PDF file - 43K, Effect of LY2228820 on MK2 phosphorylation in mouse peripheral blood mononuclear cells (PBMC) and from patients with multiple myeloma.

Published
2023
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23. Supplementary Methods, Table 1 from Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Author

Xiang S. Ye, Yong Wang, Juan A. Velasco, Courtney Tate, James J. Starling, Louis F. Stancato, Chuan Shih, Susan E. Pratt, Stephen H. Parsons, Songqing Na, Denis McCann, Mary Mader, Enrique Jambrina, Jeremy R. Graff, Raymond Gilmour, Alfonso De Dios, Edward M. Chan, Harold B. Brooks, Nathan A. Brooks, Bryan D. Anderson, and Robert M. Campbell

Abstract

PDF file - 86K, Supplemental Table 1. Kinases where LY2228820 shows >1000-fold selectivity in vitro (p38 MAPK vs. other kinase).

Published
2023
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24. Supplementary Figures 1 and 2 and Supplementary Tables 1 through 3 from A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models

Author

Jian Du, Alfonso de Dios, Richard B. Gaynor, James J. Starling, Xiang S. Ye, Amit Aggarwal, Song Wu, Shuyu Li, Yuewei Qian, Gregory P. Donoho, Aimee B. Lin, Bart W. Halstead, Sean E. Sissons, Douglas Zeckner, Robert T. Foreman, Timothy I. Meier, Phillip W. Iversen, Damien M. Cronier, Rose T. Ajamie, Graham N. Wishart, Raquel Torrres, Santiago Carballares, Kevin R. Fales, Emiko L. Kreklau, Maria J. Lallena, and Tinggui Yin

Abstract

PDF - 1128K, Figure S1. Knockdown of CDK7 and CDK9 can inhibit RNAP II CTD P-Ser2 and P-Ser5. Figure S2. LY2857785 and flavopiridol inhibit MCL-1, XIAP protein expression and induce CASP-3 and cleaved PARP in AML cell MV-4-11. Table S1. LY2857785 inhibits solid tumor cell proliferation and induces apoptosis. Table S2. 261 probsets gene signature in sens and res cell lines. Table S3. LY2857785 inhibits proliferation of normal human hematopoietic cells in vitro.

Published
2023
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26. Supplementary Figures S1-S4 from The CDK4/6 Inhibitor LY2835219 Overcomes Vemurafenib Resistance Resulting from MAPK Reactivation and Cyclin D1 Upregulation

Author

Sheng-Bin Peng, Richard P. Beckmann, James J. Starling, Edward M. Chan, Sean G. Buchanan, Youyan Zhang, Robert D. Van Horn, Lysiane Huber, Teresa F. Burke, and Vipin Yadav

Abstract

Supplementary figure S1 describes the molecular mechanisms of resistance across vemurafenib-resistant cell line models. Supplementary figure S2 serves as a repeat of figure 3a describing development of in vivo model of resistance, and demonstrates the effect of vemurafenib withdrawl on the resistant tumors. Supplementary figure S3 describes the effect of vemurafenib treatment on MAPK pathway inhibition in A375-RV2 cells. Supplementary figure S4 shows that selective cyclin D1 knockdown or CDK4/6 inhibition induces apoptosis in A375-R1 and M14-R vemurafenib-resistant melanoma cells.

Published
2023
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27. Supplementary Figure 2 from Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Author

Xiang S. Ye, Yong Wang, Juan A. Velasco, Courtney Tate, James J. Starling, Louis F. Stancato, Chuan Shih, Susan E. Pratt, Stephen H. Parsons, Songqing Na, Denis McCann, Mary Mader, Enrique Jambrina, Jeremy R. Graff, Raymond Gilmour, Alfonso De Dios, Edward M. Chan, Harold B. Brooks, Nathan A. Brooks, Bryan D. Anderson, and Robert M. Campbell

Abstract

PDF file - 90K, shRNA silencing of p38a MAPK in U-87MG glioma (Westerns and xenograft tumor growth data).

Published
2023
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28. Supplementary Table 2 from A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models

Author

Jian Du, Alfonso de Dios, Richard B. Gaynor, James J. Starling, Xiang S. Ye, Amit Aggarwal, Song Wu, Shuyu Li, Yuewei Qian, Gregory P. Donoho, Aimee B. Lin, Bart W. Halstead, Sean E. Sissons, Douglas Zeckner, Robert T. Foreman, Timothy I. Meier, Phillip W. Iversen, Damien M. Cronier, Rose T. Ajamie, Graham N. Wishart, Raquel Torrres, Santiago Carballares, Kevin R. Fales, Emiko L. Kreklau, Maria J. Lallena, and Tinggui Yin

Abstract

XLSX - 54K, Table S2. 261 probsets gene signature in sens and res cell lines in Excel format.

Published
2023
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29. Data from A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models

Author

Jian Du, Alfonso de Dios, Richard B. Gaynor, James J. Starling, Xiang S. Ye, Amit Aggarwal, Song Wu, Shuyu Li, Yuewei Qian, Gregory P. Donoho, Aimee B. Lin, Bart W. Halstead, Sean E. Sissons, Douglas Zeckner, Robert T. Foreman, Timothy I. Meier, Phillip W. Iversen, Damien M. Cronier, Rose T. Ajamie, Graham N. Wishart, Raquel Torrres, Santiago Carballares, Kevin R. Fales, Emiko L. Kreklau, Maria J. Lallena, and Tinggui Yin

Abstract

DNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain (CTD) kinases, including CDK9, are serine/threonine kinases known to regulate transcriptional initiation and elongation by phosphorylating Ser 2, 5, and 7 residues on CTD. Given the reported dysregulation of these kinases in some cancers, we asked whether inhibiting CDK9 may induce stress response and preferentially kill tumor cells. Herein, we describe a potent CDK9 inhibitor, LY2857785, that significantly reduces RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target, especially in hematologic malignancies. Mol Cancer Ther; 13(6); 1442–56. ©2014 AACR.

Published
2023
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30. Supplementary Figures S1 - S7, Tables S1 - S2 from Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120

Author

Sheng-Bin Peng, Gregory D. Plowman, James J. Starling, James R. Henry, Ilaria Conti, Lysiane Huber, Yong Gang Yue, Swee Seong Wong, Igor Mochalkin, Vipin Yadav, Sean Buchanan, Tinggui Yin, Robert D. Van Horn, Youyan Zhang, and Shih-Hsun Chen

Abstract

Supplementary Figure S1. Validation of BRAF deletion in BxPC-3 cells by Sanger's sequencing method. Supplementary Figure S2. BRAF deletion (deltaBRAF), but not WT BRAF, is able to transform cells. Supplementary Figure S3. Validation of in situ PLA in HeLa and HEK293 cells. Supplementary Figure S4. Phospho-CRAF and MAPK activation in selected tumor cells with BRAF alteration or KRAS mutation. Supplementary Figure S5. Phospho-MEK and ERK inhibition by dabrafenib in tumor cells harboring BRAF deletion. Supplementary Figure S6. In vitro effects of MAPK inhibitors on tumor cells harboring BRAF deletions. Supplementary Table S1. Novel somatic BRAF in-frame deletions from cancer cell lines and patient samples. Supplementary Figure S7. LY3009120, but not vemurafenib, exhibited significant tumor growth inhibition and regression in lung and pancreatic tumor xenograft models harboring the BRAF deletions without significant body weight loss. Supplementary Table S2. IC50 of LY3009120 and vemurafenib against tumor cells with atypical BRAF mutations.

Published
2023
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31. Optimal Flow—A Pilot Study Balancing Sheep Movement and Welfare in Abattoirs

Author

Melissa J. Starling, Elyssa Payne, and Paul McGreevy

Subjects
herding dogs, working dogs, livestock handling, livestock stress, animal welfare, lairage, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

Abattoirs are faced with the challenge of moving livestock efficiently through the plant, while also engaging in handling practices that assure good animal welfare. Achieving optimal outcomes for both of these goals can bring them into conflict. An additional source of conflict can arise from the design of the abattoir. These problems are compounded by the dearth of research available to inform how livestock should be handled to achieve all of these goals. We applied the concept of ‘Optimal Flow’ to describe conditions under which rate of movement is maximised while overt signs of distress in sheep are minimised. Effectively, this represents the point at which trade-offs between speed and welfare converge. The current pilot study examined the behavioural interactions between humans (n = 5), livestock herding dogs (n = 7), and sheep (n = 3235) in a large Australian abattoir to describe the factors associated with an increase or decrease in rate of sheep movement per minute. It revealed that distress behaviours in sheep were associated with dog presence and with a decrease in livestock movement rate. However, we found that as sheep density increased, there was increased livestock movement rate as well as an elevated incidence of distress behaviours. Optimal Flow at this abattoir was achieved by maintaining sheep at lower densities. Our report discusses the possible confounds in this interpretation.

Published
2021
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32. Eptinezumab improved patient-reported outcomes in patients with migraine and medication-overuse headache : Subgroup analysis of the randomized PROMISE-2 trial

Author

Amaal J. Starling, Robert P. Cowan, Dawn C. Buse, Hans‐Christoph Diener, Michael J. Marmura, Joe Hirman, Thomas Brevig, and Roger Cady

Subjects
Neurology, Medizin, Neurology (clinical)
Abstract

Objective: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). Background: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. Methods: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). Results: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was “much” or “very much” improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. Conclusions: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.

Published
2023

34. Behavioural risks in male dogs with minimal lifetime exposure to gonadal hormones may complicate population-control benefits of desexing.

Author

Paul D McGreevy, Bethany Wilson, Melissa J Starling, and James A Serpell

Subjects
Medicine, Science
Abstract

Castration of dogs is a widespread practise with clear justification in population control and knock-on benefits for animal welfare. Deleterious behavioural consequences of castration are believed to be negligible. Gonadectomy is widely recommended as part of a multi-factorial approach to prevent problems including aggression in dogs. However, the consequences of early castration on health are still being debated. The current study focused on the reported behaviour of 6,235 male dogs castrated before 520 weeks of life for reasons other than behavioural management, and calculated their percentage lifetime exposure to gonadal hormones (PLGH) as a proportion of their age at the time of being reported to the online Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Forty behaviors differed between entire and castrated dogs, of which 25 were associated with PLGH and 14 with age-at-castration (AAC). Only 2 behaviours, indoor urine marking and howling when left alone, were significantly more likely in dogs with longer PLGH. In contrast, longer PLGH was associated with significantly reduced reporting of 26 (mostly unwelcome) behaviours. Of these, 8 related to fearfulness and 7 to aggression. The current data suggest that dogs' tendency to show numerous behaviours can be influenced by the timing of castration. They indicate how dog behaviour matures when gonadal hormones are allowed to have their effect. The differences reported here between undesirable behaviours of castrated and intact dogs were in the range of 5.04% and 12.31%, suggesting that, for some dogs, partial or complete denial of puberty may reduce indoor urine-marking but have many other undesirable consequences. Veterinarians may use these data to discuss unwelcome consequences with owners of male dogs before castration.

Published
2018
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35. OnabotulinumtoxinA in the treatment of patients with chronic migraine: clinical evidence and experience

Author

Chia-Chun Chiang and Amaal J. Starling

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4–2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Since then, numerous studies have been performed investigating the short-term and long-term benefits, risks and complications of the use of onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose of this narrative review is to describe the currently available clinical evidence for the use of onabotulinumtoxinA injections for treating patients with chronic migraine.

Published
2017
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36. Static Subjective Visual Vertical (SVV) in Patients with Vestibular Migraine

Author

Jamie M. Bogle, Ashley Zaleski King, Nicholas Deep, Peter Weisskopf, and Amaal J. Starling

Subjects
Speech and Hearing
Abstract

Background Vestibular migraine (VM) is one of the common causes of episodic dizziness, but it is underdiagnosed and poorly understood. Previous research suggests that otolith reflex pathway performance is often impaired in this patient group, leading to altered perception of roll plane stimuli. Clinically, this perception can be measured with subjective visual vertical (SVV) testing. Purpose The aim of this study is to compare static SVV performance (absolute mean SVV tilt, variance) in a cohort of patients diagnosed with VM to results obtained from clinically derived normative data. Study Design Retrospective case review. Study Sample Ninety-four consecutive patients between 18 and 65 years of age diagnosed with VM were included in this comparison to clinically derived normative data. Data Collection and Analysis Retrospective chart review was completed. Demographic data, symptom report, and vestibular laboratory results were documented. SVV performance was documented in terms of absolute mean SVV tilt and response variance. Results Abnormal mean SVV tilt was described in 54% (n = 51) of patients with VM. Including abnormal response variance increased those identified with abnormal presentation to 67% (n = 63). Laboratory findings were insignificant for semicircular canal function, but of those with abnormal ocular vestibular myogenic potential results (n = 30), 77% (n = 23) demonstrated both abnormal SVV and utriculo-ocular reflex performance. There were no associations noted for SVV performance and demographic or other self-report variables. Conclusion Absolute mean SVV tilt and response variance are often abnormal in patients diagnosed with VM. These findings support theories suggesting atypical intralabyrinthine integration within the vestibular nuclei and cerebellar nodular pathways.

Published
2022

37. Impact of diabetes on the management and outcomes in atrial fibrillation:an analysis from the ESC-EHRA EORP-AF Long-Term General Registry

Author

Wern Yew Ding, Agnieszka Kotalczyk, Giuseppe Boriani, Francisco Marin, Carina Blomström-Lundqvist, Tatjana S. Potpara, Laurent Fauchier, Gregory.Y.H. Lip, G. Boriani, G.Y.H. Lip, L. Tavazzi, A.P. Maggioni, G.-A. Dan, T. Potpara, M. Nabauer, F. Marin, Z. Kalarus, A. Goda, G. Mairesse, T. Shalganov, L. Antoniades, M. Taborsky, S. Riahi, P. Muda, I. García Bolao, O. Piot, K. Etsadashvili, E. Simantirakis, M. Haim, A. Azhari, J. Najafian, M. Santini, E. Mirrakhimov, K.A. Kulzida, A. Erglis, L. Poposka, M. Burg, H. Crijns, Ö. Erküner, D. Atar, R. Lenarczyk, M. Martins Oliveira, D. Shah, E. Serdechnaya, E. Diker, D. Lane, E. Zëra, U. Ekmekçiu, V. Paparisto, M. Tase, H. Gjergo, J. Dragoti, M. Ciutea, N. Ahadi, Z. el Husseini, M. Raepers, J. Leroy, P. Haushan, A. Jourdan, C. Lepiece, L. Desteghe, J. Vijgen, P. Koopman, G. Van Genechten, H. Heidbuchel, T. Boussy, M. De Coninck, H. Van Eeckhoutte, N. Bouckaert, A. Friart, J. Boreux, C. Arend, P. Evrard, L. Stefan, E. Hoffer, J. Herzet, M. Massoz, C. Celentano, M. Sprynger, L. Pierard, P. Melon, B. Van Hauwaert, C. Kuppens, D. Faes, D. Van Lier, A. Van Dorpe, A. Gerardy, O. Deceuninck, O. Xhaet, F. Dormal, E. Ballant, D. Blommaert, D. Yakova, M. Hristov, T. Yncheva, N. Stancheva, S. Tisheva, M. Tokmakova, F. Nikolov, D. Gencheva, B. Kunev, M. Stoyanov, D. Marchov, V. Gelev, V. Traykov, A. Kisheva, H. Tsvyatkov, R. Shtereva, S. Bakalska-Georgieva, S. Slavcheva, Y. Yotov, M. Kubíčková, A. Marni Joensen, A. Gammelmark, L. Hvilsted Rasmussen, P. Dinesen, S. Krogh Venø, B. Sorensen, A. Korsgaard, K. Andersen, C. Fragtrup Hellum, A. Svenningsen, O. Nyvad, P. Wiggers, O. May, A. Aarup, B. Graversen, L. Jensen, M. Andersen, M. Svejgaard, S. Vester, S. Hansen, V. Lynggaard, M. Ciudad, R. Vettus, A. Maestre, S. Castaño, S. Cheggour, J. Poulard, V. Mouquet, S. Leparrée, J. Bouet, J. Taieb, A. Doucy, H. Duquenne, A. Furber, J. Dupuis, J. Rautureau, M. Font, P. Damiano, M. Lacrimini, J. Abalea, S. Boismal, T. Menez, J. Mansourati, G. Range, H. Gorka, C. Laure, C. Vassalière, N. Elbaz, N. Lellouche, K. Djouadi, F. Roubille, D. Dietz, J. Davy, M. Granier, P. Winum, C. Leperchois-Jacquey, H. Kassim, E. Marijon, J. Le Heuzey, J. Fedida, C. Maupain, C. Himbert, E. Gandjbakhch, F. Hidden-Lucet, G. Duthoit, N. Badenco, T. Chastre, X. Waintraub, M. Oudihat, J. Lacoste, C. Stephan, H. Bader, N. Delarche, L. Giry, D. Arnaud, C. Lopez, F. Boury, I. Brunello, M. Lefèvre, R. Mingam, M. Haissaguerre, M. Le Bidan, D. Pavin, V. Le Moal, C. Leclercq, T. Beitar, I. Martel, A. Schmid, N. Sadki, C. Romeyer-Bouchard, A. Da Costa, I. Arnault, M. Boyer, C. Piat, N. Lozance, S. Nastevska, A. Doneva, B. Fortomaroska Milevska, B. Sheshoski, K. Petroska, N. Taneska, N. Bakrecheski, K. Lazarovska, S. Jovevska, V. Ristovski, A. Antovski, E. Lazarova, I. Kotlar, J. Taleski, S. Kedev, N. Zlatanovik, S. Jordanova, T. Bajraktarova Proseva, S. Doncovska, D. Maisuradze, A. Esakia, E. Sagirashvili, K. Lartsuliani, N. Natelashvili, N. Gumberidze, R. Gvenetadze, N. Gotonelia, N. Kuridze, G. Papiashvili, I. Menabde, S. Glöggler, A. Napp, C. Lebherz, H. Romero, K. Schmitz, M. Berger, M. Zink, S. Köster, J. Sachse, E. Vonderhagen, G. Soiron, K. Mischke, R. Reith, M. Schneider, W. Rieker, D. Boscher, A. Taschareck, A. Beer, D. Oster, O. Ritter, J. Adamczewski, S. Walter, A. Frommhold, E. Luckner, J. Richter, M. Schellner, S. Landgraf, S. Bartholome, R. Naumann, J. Schoeler, D. Westermeier, F. William, K. Wilhelm, M. Maerkl, R. Oekinghaus, M. Denart, M. Kriete, U. Tebbe, T. Scheibner, M. Gruber, A. Gerlach, C. Beckendorf, L. Anneken, M. Arnold, S. Lengerer, Z. Bal, C. Uecker, H. Förtsch, S. Fechner, V. Mages, E. Martens, H. Methe, T. Schmidt, B. Schaeffer, B. Hoffmann, J. Moser, K. Heitmann, S. Willems, C. Klaus, I. Lange, M. Durak, E. Esen, F. Mibach, H. Mibach, A. Utech, M. Gabelmann, R. Stumm, V. Ländle, C. Gartner, C. Goerg, N. Kaul, S. Messer, D. Burkhardt, C. Sander, R. Orthen, S. Kaes, A. Baumer, F. Dodos, A. Barth, G. Schaeffer, J. Gaertner, J. Winkler, A. Fahrig, J. Aring, I. Wenzel, S. Steiner, A. Kliesch, E. Kratz, K. Winter, P. Schneider, A. Haag, I. Mutscher, R. Bosch, J. Taggeselle, S. Meixner, A. Schnabel, A. Shamalla, H. Hötz, A. Korinth, C. Rheinert, G. Mehltretter, B. Schön, N. Schön, A. Starflinger, E. Englmann, G. Baytok, T. Laschinger, G. Ritscher, A. Gerth, D. Dechering, L. Eckardt, M. Kuhlmann, N. Proskynitopoulos, J. Brunn, K. Foth, C. Axthelm, H. Hohensee, K. Eberhard, S. Turbanisch, N. Hassler, A. Koestler, G. Stenzel, D. Kschiwan, M. Schwefer, S. Neiner, S. Hettwer, M. Haeussler-Schuchardt, R. Degenhardt, S. Sennhenn, M. Brendel, A. Stoehr, W. Widjaja, S. Loehndorf, A. Logemann, J. Hoskamp, J. Grundt, M. Block, R. Ulrych, A. Reithmeier, V. Panagopoulos, C. Martignani, D. Bernucci, E. Fantecchi, I. Diemberger, M. Ziacchi, M. Biffi, P. Cimaglia, J. Frisoni, I. Giannini, S. Boni, S. Fumagalli, S. Pupo, A. Di Chiara, P. Mirone, F. Pesce, C. Zoccali, V.L. Malavasi, A. Mussagaliyeva, B. Ahyt, Z. Salihova, K. Koshum-Bayeva, A. Kerimkulova, A. Bairamukova, B. Lurina, R. Zuzans, S. Jegere, I. Mintale, K. Kupics, K. Jubele, O. Kalejs, K. Vanhear, M. Cachia, E. Abela, S. Warwicker, T. Tabone, R. Xuereb, D. Asanovic, D. Drakalovic, M. Vukmirovic, N. Pavlovic, L. Music, N. Bulatovic, A. Boskovic, H. Uiterwaal, N. Bijsterveld, J. De Groot, J. Neefs, N. van den Berg, F. Piersma, A. Wilde, V. Hagens, J. Van Es, J. Van Opstal, B. Van Rennes, H. Verheij, W. Breukers, G. Tjeerdsma, R. Nijmeijer, D. Wegink, R. Binnema, S. Said, S. Philippens, W. van Doorn, T. Szili-Torok, R. Bhagwandien, P. Janse, A. Muskens, M. van Eck, R. Gevers, N. van der Ven, A. Duygun, B. Rahel, J. Meeder, A. Vold, C. Holst Hansen, I. Engset, B. Dyduch-Fejklowicz, E. Koba, M. Cichocka, A. Sokal, A. Kubicius, E. Pruchniewicz, A. Kowalik-Sztylc, W. Czapla, I. Mróz, M. Kozlowski, T. Pawlowski, M. Tendera, A. Winiarska-Filipek, A. Fidyk, A. Slowikowski, M. Haberka, M. Lachor-Broda, M. Biedron, Z. Gasior, M. Kołodziej, M. Janion, I. Gorczyca-Michta, B. Wozakowska-Kaplon, M. Stasiak, P. Jakubowski, T. Ciurus, J. Drozdz, M. Simiera, P. Zajac, T. Wcislo, P. Zycinski, J. Kasprzak, A. Olejnik, E. Harc-Dyl, J. Miarka, M. Pasieka, M. Ziemińska-Łuć, W. Bujak, A. Śliwiński, A. Grech, J. Morka, K. Petrykowska, M. Prasał, G. Hordyński, P. Feusette, P. Lipski, A. Wester, W. Streb, J. Romanek, P. Woźniak, M. Chlebuś, P. Szafarz, W. Stanik, M. Zakrzewski, J. Kaźmierczak, A. Przybylska, E. Skorek, H. Błaszczyk, M. Stępień, S. Szabowski, W. Krysiak, M. Szymańska, J. Karasiński, J. Blicharz, M. Skura, K. Hałas, L. Michalczyk, Z. Orski, K. Krzyżanowski, A. Skrobowski, L. Zieliński, M. Tomaszewska-Kiecana, M. Dłużniewski, M. Kiliszek, M. Peller, M. Budnik, P. Balsam, G. Opolski, A. Tymińska, K. Ozierański, A. Wancerz, A. Borowiec, E. Majos, R. Dabrowski, H. Szwed, A. Musialik-Lydka, A. Leopold-Jadczyk, E. Jedrzejczyk-Patej, M. Koziel, M. Mazurek, K. Krzemien-Wolska, P. Starosta, E. Nowalany-Kozielska, A. Orzechowska, M. Szpot, M. Staszel, S. Almeida, H. Pereira, L. Brandão Alves, R. Miranda, L. Ribeiro, F. Costa, F. Morgado, P. Carmo, P. Galvao Santos, R. Bernardo, P. Adragão, G. Ferreira da Silva, M. Peres, M. Alves, M. Leal, A. Cordeiro, P. Magalhães, P. Fontes, S. Leão, A. Delgado, A. Costa, B. Marmelo, B. Rodrigues, D. Moreira, J. Santos, L. Santos, A. Terchet, D. Darabantiu, S. Mercea, V. Turcin Halka, A. Pop Moldovan, A. Gabor, B. Doka, G. Catanescu, H. Rus, L. Oboroceanu, E. Bobescu, R. Popescu, A. Dan, A. Buzea, I. Daha, G. Dan, I. Neuhoff, M. Baluta, R. Ploesteanu, N. Dumitrache, M. Vintila, A. Daraban, C. Japie, E. Badila, H. Tewelde, M. Hostiuc, S. Frunza, E. Tintea, D. Bartos, A. Ciobanu, I. Popescu, N. Toma, C. Gherghinescu, D. Cretu, N. Patrascu, C. Stoicescu, C. Udroiu, G. Bicescu, V. Vintila, D. Vinereanu, M. Cinteza, R. Rimbas, M. Grecu, A. Cozma, F. Boros, M. Ille, O. Tica, R. Tor, A. Corina, A. Jeewooth, B. Maria, C. Georgiana, C. Natalia, D. Alin, D. Dinu-Andrei, M. Livia, R. Daniela, R. Larisa, S. Umaar, T. Tamara, M. Ioachim Popescu, D. Nistor, I. Sus, O. Coborosanu, N. Alina-Ramona, R. Dan, L. Petrescu, G. Ionescu, C. Vacarescu, E. Goanta, M. Mangea, A. Ionac, C. Mornos, D. Cozma, S. Pescariu, E. Solodovnicova, I. Soldatova, J. Shutova, L. Tjuleneva, T. Zubova, V. Uskov, D. Obukhov, G. Rusanova, N. Isakova, S. Odinsova, T. Arhipova, E. Kazakevich, O. Zavyalova, T. Novikova, I. Riabaia, S. Zhigalov, E. Drozdova, I. Luchkina, Y. Monogarova, D. Hegya, L. Rodionova, V. Nevzorova, O. Lusanova, A. Arandjelovic, D. Toncev, L. Vukmirovic, M. Radisavljevic, M. Milanov, N. Sekularac, M. Zdravkovic, S. Hinic, S. Dimkovic, T. Acimovic, J. Saric, S. Radovanovic, A. Kocijancic, B. Obrenovic-Kircanski, D. Kalimanovska Ostric, D. Simic, I. Jovanovic, I. Petrovic, M. Polovina, M. Vukicevic, M. Tomasevic, N. Mujovic, N. Radivojevic, O. Petrovic, S. Aleksandric, V. Kovacevic, Z. Mijatovic, B. Ivanovic, M. Tesic, A. Ristic, B. Vujisic-Tesic, M. Nedeljkovic, A. Karadzic, A. Uscumlic, M. Prodanovic, M. Zlatar, M. Asanin, B. Bisenic, V. Vasic, Z. Popovic, D. Djikic, M. Sipic, V. Peric, B. Dejanovic, N. Milosevic, S. Backovic, A. Stevanovic, A. Andric, B. Pencic, M. Pavlovic-Kleut, V. Celic, M. Pavlovic, M. Petrovic, M. Vuleta, N. Petrovic, S. Simovic, Z. Savovic, S. Milanov, G. Davidovic, V. Iric-Cupic, D. Djordjevic, M. Damjanovic, S. Zdravkovic, V. Topic, D. Stanojevic, M. Randjelovic, R. Jankovic-Tomasevic, V. Atanaskovic, S. Antic, D. Simonovic, M. Stojanovic, S. Stojanovic, V. Mitic, V. Ilic, D. Petrovic, M. Deljanin Ilic, S. Ilic, V. Stoickov, S. Markovic, A. Mijatovic, D. Tanasic, G. Radakovic, J. Peranovic, N. Panic-Jelic, O. Vujadinovic, P. Pajic, S. Bekic, S. Kovacevic, A. García Fernandez, A. Perez Cabeza, M. Anguita, L. Tercedor Sanchez, E. Mau, J. Loayssa, M. Ayarra, M. Carpintero, I. Roldán Rabadan, M. Gil Ortega, A. Tello Montoliu, E. Orenes Piñero, S. Manzano Fernández, F. Marín, A. Romero Aniorte, A. Veliz Martínez, M. Quintana Giner, G. Ballesteros, M. Palacio, O. Alcalde, I. García-Bolao, V. Bertomeu Gonzalez, F. Otero-Raviña, J. García Seara, J. Gonzalez Juanatey, N. Dayal, P. Maziarski, P. Gentil-Baron, M. Koç, E. Onrat, I.E. Dural, K. Yilmaz, B. Özin, S. Tan Kurklu, Y. Atmaca, U. Canpolat, L. Tokgozoglu, A.K. Dolu, B. Demirtas, D. Sahin, O. Ozcan Celebi, G. Gagirci, U.O. Turk, H. Ari, N. Polat, N. Toprak, M. Sucu, O. Akin Serdar, A. Taha Alper, A. Kepez, Y. Yuksel, A. Uzunselvi, S. Yuksel, M. Sahin, O. Kayapinar, T. Ozcan, H. Kaya, M.B. Yilmaz, M. Kutlu, M. Demir, C. Gibbs, S. Kaminskiene, M. Bryce, A. Skinner, G. Belcher, J. Hunt, L. Stancombe, B. Holbrook, C. Peters, S. Tettersell, A. Shantsila, K. Senoo, M. Proietti, K. Russell, P. Domingos, S. Hussain, J. Partridge, R. Haynes, S. Bahadur, R. Brown, S. McMahon, J. McDonald, K. Balachandran, R. Singh, S. Garg, H. Desai, K. Davies, W. Goddard, G. Galasko, I. Rahman, Y. Chua, O. Payne, S. Preston, O. Brennan, L. Pedley, C. Whiteside, C. Dickinson, J. Brown, K. Jones, L. Benham, R. Brady, L. Buchanan, A. Ashton, H. Crowther, H. Fairlamb, S. Thornthwaite, C. Relph, A. McSkeane, U. Poultney, N. Kelsall, P. Rice, T. Wilson, M. Wrigley, R. Kaba, T. Patel, E. Young, J. Law, C. Runnett, H. Thomas, H. McKie, J. Fuller, S. Pick, A. Sharp, A. Hunt, K. Thorpe, C. Hardman, E. Cusack, L. Adams, M. Hough, S. Keenan, A. Bowring, J. Watts, J. Zaman, K. Goffin, H. Nutt, Y. Beerachee, J. Featherstone, C. Mills, J. Pearson, L. Stephenson, S. Grant, A. Wilson, C. Hawksworth, I. Alam, M. Robinson, S. Ryan, R. Egdell, E. Gibson, M. Holland, D. Leonard, B. Mishra, S. Ahmad, H. Randall, J. Hill, L. Reid, M. George, S. McKinley, L. Brockway, W. Milligan, J. Sobolewska, J. Muir, L. Tuckis, L. Winstanley, P. Jacob, S. Kaye, L. Morby, A. Jan, T. Sewell, C. Boos, B. Wadams, C. Cope, P. Jefferey, N. Andrews, A. Getty, A. Suttling, C. Turner, K. Hudson, R. Austin, S. Howe, R. Iqbal, N. Gandhi, K. Brophy, P. Mirza, E. Willard, S. Collins, N. Ndlovu, E. Subkovas, V. Karthikeyan, L. Waggett, A. Wood, A. Bolger, J. Stockport, L. Evans, E. Harman, J. Starling, L. Williams, V. Saul, M. Sinha, L. Bell, S. Tudgay, S. Kemp, L. Frost, T. Ingram, A. Loughlin, C. Adams, M. Adams, F. Hurford, C. Owen, C. Miller, D. Donaldson, H. Tivenan, H. Button, A. Nasser, O. Jhagra, B. Stidolph, C. Brown, C. Livingstone, M. Duffy, P. Madgwick, P. Roberts, E. Greenwood, L. Fletcher, M. Beveridge, S. Earles, D. McKenzie, D. Beacock, M. Dayer, M. Seddon, D. Greenwell, F. Luxton, F. Venn, H. Mills, J. Rewbury, K. James, K. Roberts, L. Tonks, D. Felmeden, W. Taggu, A. Summerhayes, D. Hughes, J. Sutton, L. Felmeden, M. Khan, E. Walker, L. Norris, L. O'Donohoe, A. Mozid, H. Dymond, H. Lloyd-Jones, G. Saunders, D. Simmons, D. Coles, D. Cotterill, S. Beech, S. Kidd, B. Wrigley, S. Petkar, A. Smallwood, R. Jones, E. Radford, S. Milgate, S. Metherell, V. Cottam, C. Buckley, A. Broadley, D. Wood, J. Allison, K. Rennie, L. Balian, L. Howard, L. Pippard, S. Board, T. Pitt-Kerby, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Océan du Large et Variabilité Climatique (OLVAC), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Uppsala University, University of Belgrade [Belgrade], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), and Université de Tours (UT)

Subjects
Kardiologi, General Practice, Cohort, Anticoagulants, MACE, Endocrinology and Diabetes, Prognosis, [SHS]Humanities and Social Sciences, Allmänmedicin, Stroke, Risk Factors, Healthcare resource utilisation, Mortality, Prevalence, Endokrinologi och diabetes, Atrial Fibrillation, Internal Medicine, Diabetes Mellitus, Quality of Life, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, Registries, Aged
Abstract

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Published
2022
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38. Picture Perfect Pups: How Do Attributes of Photographs of Dogs in Online Rescue Profiles Affect Adoption Speed?

Author

Mizuho Nakamura, Navneet Dhand, Bethany J. Wilson, Melissa J. Starling, and Paul D. McGreevy

Subjects
dogs, welfare, adoption, rescue, morphology, breed, photographs, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

To increase the public’s awareness of and exposure to animals needing homes, PetRescue, Australia’s largest online directory of animals in need of adoption, lists all currently available animals from rescue and welfare shelters nationwide. The current study examined the photographs in the PetRescue online profiles of the three most common breeds within these data, namely, Staffordshire bull terriers (n = 3988), Labrador retrievers (n = 2246), and Jack Russell terriers (n = 2088), to identify the inferred preferences of potential adopters. By investigating the attributes of these photographs, we were able to identify visual risk factors associated with protracted lengths of stay (LOS). The longest stays were associated with dogs with erect ears and those photographed in a natural environment, i.e., 18.32 days and 19.57 days, respectively. Dogs photographed in a kennel and with mouths closed had the shortest LOS, i.e., 11.54 d and 14.44 d, respectively. Heightened awareness of the roles of photographic attributes in generating interest among potential adopters may increase the speed of adoption by guiding the creation of online profiles and selection of photos to optimise the promotion of dogs at risk of long stays.

Published
2020
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39. Ten Eleven things to facilitate participation of underrepresented groups in headache medicine research

Author

Christina L. Szperka, Cynthia E. Armand, Jessica Kiarashi, Juliana H. VanderPluym, Olivia Begasse de Dhaem, Amaal J. Starling, Yeonsoo Sara Lee, Elizabeth K. Seng, Larry Charleston, and Thilinie Rajapakse

Subjects
African american, medicine.medical_specialty, Biomedical Research, Racial Groups, Headache, Community-based participatory research, Article, Underserved Population, Neurology, Family medicine, medicine, Humans, Neurology (clinical), Patient Participation, Psychology, Minority Groups
Published
2021
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40. Descriptive Texts in Dog Profiles Associated with Length of Stay Via an Online Rescue Network

Author

Mizuho Nakamura, Navneet K. Dhand, Melissa J. Starling, and Paul D. McGreevy

Subjects
dog, welfare, adoption, descriptors, temperament, breed, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

To increase the public’s awareness of animals needing homes, PetRescue, Australia’s largest online directory of animals in need of adoption, lists animals available from rescue and welfare shelters nationwide. The current study examined the descriptions accompanying online PetRescue profiles. The demographic data and personality descriptors of 70,733 dogs were analysed for associations with LOS in shelters—with long stays being a potential proxy for low appeal. Univariable and multivariable general linear models of log-transformed LOS with personality adjectives and demographic variables were fitted and the predicted means back-transformed for presentation. Further analyses were conducted of a subset of the dataset for the four most common breeds (n = 20,198 dogs) to investigate if the influence of personality adjectives on the LOS differed by breed. The average LOS of dogs was 35.4 days (median 18 days) and was influenced by several adjectives. Across all breeds, the LOS was significantly shorter if the adjectives ‘make you proud’, ‘independent’, ‘lively’, ‘eager’ and ‘clever’ were included in the description. However, the LOS was longer if the terms ‘only dog’, ‘dominant’, ‘sensitive’ and ‘happy-go-lucky’ were included in the description. Some of the association of descriptors with relatively long LOS are difficult to explain. For example, it is unclear why the terms “obedient” and trainable” appear unappealing. The confidence adopters have in these terms and their ability to make the most of such dogs merits further exploration. As expected, the LOS differed in different breeds with the Labrador retrievers having the fastest adoption rate among the most common four breeds with an average LOS of 14.5 days. Breed had interactions with four personality adjectives (gentle, active, quiet and energetic) indicating that the adoption rate of dogs with these descriptors in their online PetRescue profiles differed by breed. This highlights an important knowledge gap, suggesting that potential adopters have differing expectations according to the breed being considered. Increased awareness of the breed-specific influence of personality adjectives on appeal to potential adopters, may enhance adoption success by allowing dogs with risk factors for low appeal to be promoted more intensively than high-appeal dogs.

Published
2019
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41. Real‐world efficacy, tolerability, and safety of ubrogepant

Author

Chia-Chun Chiang, Marlene Girardo, David W. Dodick, Jaxon K. Quillen, Karissa N. Arca, Amaal J. Starling, and Rachel B. Dunn

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Pyridines, Population, law.invention, Cohort Studies, Tertiary Care Centers, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Chronic Migraine, Randomized controlled trial, Calcitonin Gene-Related Peptide Receptor Antagonists, law, Surveys and Questionnaires, Internal medicine, Product Surveillance, Postmarketing, medicine, Humans, Pyrroles, 030212 general & internal medicine, education, Adverse effect, Aged, Aged, 80 and over, education.field_of_study, business.industry, Arizona, Headache, Middle Aged, medicine.disease, Migraine with aura, Clinical trial, Treatment Outcome, Neurology, Tolerability, Migraine, Chronic Disease, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVE To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center. BACKGROUND The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real-world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine-specific medications. METHOD This was a post-market cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1-3 months after the prescription to answer a list of standardized questions. Demographic information and additional headache history were obtained from chart review. RESULTS We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being "very satisfied" with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a "good responder" to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine

Published
2021
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42. Conceptualising the Impact of Arousal and Affective State on Training Outcomes of Operant Conditioning

Author

Paul D. McGreevy, Denis Cody, Melissa J. Starling, and Nicholas Branson

Subjects
arousal, affective state, operant conditioning, animal training, dogs, horses, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

Animal training relies heavily on an understanding of species-specific behaviour as it integrates with operant conditioning principles. Following on from recent studies showing that affective states and arousal levels may correlate with behavioural outcomes, we explore the contribution of both affective state and arousal in behavioural responses to operant conditioning. This paper provides a framework for assessing how affective state and arousal may influence the efficacy of operant training methods. It provides a series of three-dimensional conceptual graphs as exemplars to describing putative influences of both affective state and arousal on the likelihood of dogs and horses performing commonly desired behaviours. These graphs are referred to as response landscapes, and they highlight the flexibility available for improving training efficacy and the likely need for different approaches to suit animals in different affective states and at various levels of arousal. Knowledge gaps are discussed and suggestions made for bridging them.

Published
2013
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43. Effects of pre-conditioning on behavior and physiology of horses during a standardised learning task.

Author

Kate Fenner, Holly Webb, Melissa J Starling, Rafael Freire, Petra Buckley, and Paul D McGreevy

Subjects
Medicine, Science
Abstract

Rein tension is used to apply pressure to control both ridden and unridden horses. The pressure is delivered by equipment such as the bit, which may restrict voluntary movement and cause changes in behavior and physiology. Managing the effects of such pressure on arousal level and behavioral indicators will optimise horse learning outcomes. This study examined the effect of training horses to turn away from bit pressure on cardiac outcomes and behavior (including responsiveness) over the course of eight trials in a standardised learning task. The experimental procedure consisted of a resting phase, treatment/control phase, standardised learning trials requiring the horses (n = 68) to step backwards in response to bit pressure and a recovery phase. As expected, heart rate increased (P = 0.028) when the handler applied rein tension during the treatment phase. The amount of rein tension required to elicit a response during treatment was higher on the left than the right rein (P = 0.009). Total rein tension required for trials reduced (P < 0.001) as they progressed, as did time taken (P < 0.001) and steps taken (P < 0.001). The incidence of head tossing decreased (P = 0.015) with the progression of the trials and was higher (P = 0.018) for the control horses than the treated horses. These results suggest that preparing the horses for the lesson and slightly raising their arousal levels, improved learning outcomes.

Published
2017
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44. Variability of the modified Balance Error Scoring System at baseline using objective and subjective balance measures

Author

Amaal J Starling, Danielle F Leong, Jamie M Bogle, and Bert B Vargas

Subjects
athlete, baseline, concussion evaluation, modified Balance Error Scoring System, postural control, sports concussion, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Aim: To investigate preseason modified Balance Error Scoring System (mBESS) performance in a collegiate football cohort; to compare scores to an objective mobile balance measurement tool. Materials & methods: Eighty-two athletes completed simultaneous balance testing using mBESS and the King–Devick Balance Test, an objective balance measurement tool. Errors on mBESS and objective measurements in the double-leg, single-leg (SS) and tandem stances were compared. Results: Mean mBESS error score was 7.23 ± 4.65. The SS accounted for 74% of errors and 21% of athletes demonstrated the maximum error score. There was no significant correlation between mBESS score and objective balance score. Conclusion: The high variability and large number of errors in the SS raises concerns over the utility of the SS in identifying suspected concussion.

Published
2016
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45. Migraine Headache Day Response Rates and the Implications to Patient Functioning: An Evaluation of 3 Randomized Phase 3 Clinical Trials of Galcanezumab in Patients With Migraine

Author

Mallikarjuna Rettiganti, Martha D. Port, Janet H. Ford, David W. Ayer, Tobias Kurth, Linda Wietecha, Amaal J. Starling, and Dustin D. Ruff

Subjects
medicine.medical_specialty, calcitonin gene‐related peptide, Research Submissions, Calcitonin gene-related peptide, Placebo, 03 medical and health sciences, 0302 clinical medicine, Chronic Migraine, Quality of life, Internal medicine, medicine, Clinical endpoint, galcanezumab, 030212 general & internal medicine, business.industry, medicine.disease, Research Submission, Clinical trial, Clinical research, Neurology, Migraine, episodic migraine, Neurology (clinical), chronic migraine, patient‐reported outcomes, business, 030217 neurology & neurosurgery
Abstract

Objective This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient‐reported outcomes of health‐related quality of life (HRQoL) and disability categories. Background Migraine causes considerable disease‐related disability and negatively impacts HRQoL of patients. Calcitonin gene‐related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients. Methods Analyses used data from 3 double‐blind, placebo (PBO)‐controlled, phase 3 studies in adults with episodic migraine (EM) (EVOLVE‐1: N = 858 and EVOLVE‐2: N = 915) or chronic migraine (CM) (REGAIN: N = 1113). Patients were randomized 2:1:1 to subcutaneous injection of PBO, galcanezumab (GMB) 120 mg, or GMB 240 mg once monthly for 6 months in EVOLVE‐1 and ‐2 and for 3 months in REGAIN. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Patients were divided into 4 response‐level groups based on percent change from baseline (

Published
2020
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47. Is King-Devick Testing, Compared With Other Sideline Screening Tests, Superior for the Assessment of Sports-related Concussion?

Author

Karissa N. Arca, Lisa A. Marks, Marie D. Acierno, Amaal J. Starling, Bart M. Demaerschalk, and Cumara B. O’Carroll

Subjects
Male, medicine.medical_specialty, MEDLINE, Neuropsychological Tests, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Sport related concussion, 03 medical and health sciences, 0302 clinical medicine, Concussion, Humans, Medicine, Brain Concussion, Vision, Ocular, Modalities, biology, business.industry, Athletes, General Medicine, Evidence-based medicine, medicine.disease, biology.organism_classification, Test (assessment), Critical appraisal, Physical therapy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Sports
Abstract

Background Concussion affects almost 4 million individuals annually. There are many sideline screening tools available to assist in the detection of sports-related concussion. The King-Devick (K-D) test in association with Mayo Clinic utilizes rapid number naming to test saccadic eye movements in order to screen for concussion. An ideal screening tool for concussion would correctly identify all athletes with active concussion. The accuracy of K-D testing compared with other sideline screening tools is undetermined. Objective To critically assess current evidence regarding the utility of K-D testing as a sideline screening tool for acute concussion and compare K-D testing to other sideline concussion assessments. Methods The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of concussion neurology and neuro-ophthalmology. Results A recent meta-analysis was selected for critical appraisal. Cohorts analyzing athletes with sports-related concussion were selected, and utilized K-D testing as the main baseline and sideline assessment of concussion. K-D testing was found to have a high sensitivity and specificity for detecting concussion when there was worsening from baseline. Conclusion K-D testing has high sensitivity and specificity for detecting sideline concussion. Compared with other sideline screening tools that do not include vision testing, it has greater accuracy. Screening for concussion is optimized when multiple testing modalities are used in conjunction.

Published
2020
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48. Cutaneous heat and light-induced pain thresholds in post-traumatic headache attributed to mild traumatic brain injury

Author

Amaal J. Starling, Melissa M. Cortez, Nicholas R. Jarvis, Nan Zhang, Frank Porreca, Catherine D. Chong, and Todd J. Schwedt

Subjects
Cohort Studies, Pain Threshold, Hot Temperature, Neurology, Hyperalgesia, Photophobia, Humans, Pain, Post-Traumatic Headache, Neurology (clinical), Brain Concussion
Abstract

The purpose of this study was to characterize cutaneous heat and light-induced pain thresholds in people with post-traumatic headache (PTH) compared with healthy controls (HCs).Photophobia and allodynia are common in PTH, and there is emerging evidence to support multimodal sensory dysfunction.In this age- and sex-matched cohort study, individuals with PTH (n = 20) and HCs (n = 20), aged 18-65 years, were recruited from an institutional database of research volunteers, from the concussion clinic, and via the use of approved flyers posted on the Mayo Clinic Campus in Scottsdale, Arizona. Participants were assessed using the Allodynia Symptom Checklist (ASC-12), Photosensitivity Assessment Questionnaire (PAQ), State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). Quantitative sensory testing quantified heat pain thresholds. A light stimulation device quantified light-induced pain thresholds. Subsequently, heat pain thresholds were obtained immediately, 10, and 40 min after a bright light stressor.The mean photophobia symptom severity score, based on the PAQ, was higher in participants with PTH compared with HCs, mean 0.62 (SD = 0.25) versus mean 0.24 (SD = 0.24), p 0.001. Light-induced pain thresholds were lower in participants with PTH (median = 90.5 lux and quartiles = 17.8 to 378.5) compared with HCs (median = 863.5 lux and quartiles = 519.9 to 4906.5) and were independent from BDI and STAI (p 0.001). Allodynia scores did not differ between participants with PTH and HCs after adjusting for BDI and STAI scores. Baseline forehead heat pain thresholds were not different, participants with PTH mean 41.9°C (SD = 0.89) versus HCs mean 44.3°C (SD = 0.89), p = 0.061; however, forearm heat pain thresholds were lower in participants with PTH compared with HCs, mean 40.8°C (SD = 0.80) versus mean 44.4°C (SD = 0.80), p = 0.002. The forehead heat pain threshold change from baseline post bright light stressor in participants with PTH versus HCs was different immediately (mean -1.2 (SD = 0.53), p = 0.025), 10 min (mean -1.8 (SD = 0.74), p = 0.015), and 40 min (mean -1.8 (SD = 0.88), p = 0.047). The forearm heat pain threshold change immediately post bright light stressor in participants with PTH versus HCs was different, mean -1.9°C (SD = 0.58), p = 0.001, however, not different at 10 and 40 min.Photophobia is higher and light-induced pain thresholds are lower in participants with PTH. Exposure to a light stressor reduced heat pain thresholds in participants with PTH immediately post bright light stressor, but not in HCs. This study provides evidence for multimodal sensory dysfunction in people with PTH.

Published
2022

49. Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EORP atrial fibrillation general long-term registry

Author

Marco Vitolo, Vincenzo L. Malavasi, Marco Proietti, Igor Diemberger, Laurent Fauchier, Francisco Marin, Michael Nabauer, Tatjana S. Potpara, Gheorghe-Andrei Dan, Zbigniew Kalarus, Luigi Tavazzi, Aldo Pietro Maggioni, Deirdre A. Lane, Gregory Y.H. Lip, Giuseppe Boriani, G. Boriani, G.Y.H. Lip, L. Tavazzi, A.P. Maggioni, G-A. Dan, T. Potpara, M. Nabauer, F. Marin, Z. Kalarus, L. Fauchier, A. Goda, G. Mairesse, T. Shalganov, L. Antoniades, M. Taborsky, S. Riahi, P. Muda, I. García Bolao, O. Piot, K. Etsadashvili, M. Haim, A. Azhari, J. Najafian, M. Santini, E. Mirrakhimov, K. Kulzida, A. Erglis, L. Poposka, M.R. Burg, H. Crijns, Ö. Erküner, D. Atar, R. Lenarczyk, M. Martins Oliveira, D. Shah, E. Serdechnaya, E. Diker, E. Zëra, U. Ekmekçiu, V. Paparisto, M. Tase, H. Gjergo, J. Dragoti, M. Ciutea, N. Ahadi, Z. el Husseini, M. Raepers, J. Leroy, P. Haushan, A. Jourdan, C. Lepiece, L. Desteghe, J. Vijgen, P. Koopman, G. Van Genechten, H. Heidbuchel, T. Boussy, M. De Coninck, H. Van Eeckhoutte, N. Bouckaert, A. Friart, J. Boreux, C. Arend, P. Evrard, L. Stefan, E. Hoffer, J. Herzet, M. Massoz, C. Celentano, M. Sprynger, L. Pierard, P. Melon, B. Van Hauwaert, C. Kuppens, D. Faes, D. Van Lier, A. Van Dorpe, A. Gerardy, O. Deceuninck, O. Xhaet, F. Dormal, E. Ballant, D. Blommaert, D. Yakova, M. Hristov, T. Yncheva, N. Stancheva, S. Tisheva, M. Tokmakova, F. Nikolov, D. Gencheva, B. Kunev, M. Stoyanov, D. Marchov, V. Gelev, V. Traykov, A. Kisheva, H. Tsvyatkov, R. Shtereva, S. Bakalska-Georgieva, S. Slavcheva, Y. Yotov, M. Kubíčková, A. Marni Joensen, A. Gammelmark, L. Hvilsted Rasmussen, P. Dinesen, S. Krogh Venø, B. Sorensen, A. Korsgaard, K. Andersen, C. Fragtrup Hellum, A. Svenningsen, O. Nyvad, P. Wiggers, O. May, A. Aarup, B. Graversen, L. Jensen, M. Andersen, M. Svejgaard, S. Vester, S. Hansen, V. Lynggaard, M. Ciudad, R. Vettus, A. Maestre, S. Castaño, S. Cheggour, J. Poulard, V. Mouquet, S. Leparrée, J. Bouet, J. Taieb, A. Doucy, H. Duquenne, A. Furber, J. Dupuis, J. Rautureau, M. Font, P. Damiano, M. Lacrimini, J. Abalea, S. Boismal, T. Menez, J. Mansourati, G. Range, H. Gorka, C. Laure, C. Vassalière, N. Elbaz, N. Lellouche, K. Djouadi, F. Roubille, D. Dietz, J. Davy, M. Granier, P. Winum, C. Leperchois-Jacquey, H. Kassim, E. Marijon, J. Le Heuzey, J. Fedida, C. Maupain, C. Himbert, E. Gandjbakhch, F. Hidden-Lucet, G. Duthoit, N. Badenco, T. Chastre, X. Waintraub, M. Oudihat, J. Lacoste, C. Stephan, H. Bader, N. Delarche, L. Giry, D. Arnaud, C. Lopez, F. Boury, I. Brunello, M. Lefèvre, R. Mingam, M. Haissaguerre, M. Le Bidan, D. Pavin, V. Le Moal, C. Leclercq, T. Beitar, I. Martel, A. Schmid, N. Sadki, C. Romeyer-Bouchard, A. Da Costa, I. Arnault, M. Boyer, C. Piat, N. Lozance, S. Nastevska, A. Doneva, B. Fortomaroska Milevska, B. Sheshoski, K. Petroska, N. Taneska, N. Bakrecheski, K. Lazarovska, S. Jovevska, V. Ristovski, A. Antovski, E. Lazarova, I. Kotlar, J. Taleski, S. Kedev, N. Zlatanovik, S. Jordanova, T. Bajraktarova Proseva, S. Doncovska, D. Maisuradze, A. Esakia, E. Sagirashvili, K. Lartsuliani, N. Natelashvili, N. Gumberidze, R. Gvenetadze, N. Gotonelia, N. Kuridze, G. Papiashvili, I. Menabde, S. Glöggler, A. Napp, C. Lebherz, H. Romero, K. Schmitz, M. Berger, M. Zink, S. Köster, J. Sachse, E. Vonderhagen, G. Soiron, K. Mischke, R. Reith, M. Schneider, W. Rieker, D. Boscher, A. Taschareck, A. Beer, D. Oster, O. Ritter, J. Adamczewski, S. Walter, A. Frommhold, E. Luckner, J. Richter, M. Schellner, S. Landgraf, S. Bartholome, R. Naumann, J. Schoeler, D. Westermeier, F. William, K. Wilhelm, M. Maerkl, R. Oekinghaus, M. Denart, M. Kriete, U. Tebbe, T. Scheibner, M. Gruber, A. Gerlach, C. Beckendorf, L. Anneken, M. Arnold, S. Lengerer, Z. Bal, C. Uecker, H. Förtsch, S. Fechner, V. Mages, E. Martens, H. Methe, T. Schmidt, B. Schaeffer, B. Hoffmann, J. Moser, K. Heitmann, S. Willems, C. Klaus, I. Lange, M. Durak, E. Esen, F. Mibach, H. Mibach, A. Utech, M. Gabelmann, R. Stumm, V. Ländle, C. Gartner, C. Goerg, N. Kaul, S. Messer, D. Burkhardt, C. Sander, R. Orthen, S. Kaes, A. Baumer, F. Dodos, A. Barth, G. Schaeffer, J. Gaertner, J. Winkler, A. Fahrig, J. Aring, I. Wenzel, S. Steiner, A. Kliesch, E. Kratz, K. Winter, P. Schneider, A. Haag, I. Mutscher, R. Bosch, J. Taggeselle, S. Meixner, A. Schnabel, A. Shamalla, H. Hötz, A. Korinth, C. Rheinert, G. Mehltretter, B. Schön, N. Schön, A. Starflinger, E. Englmann, G. Baytok, T. Laschinger, G. Ritscher, A. Gerth, D. Dechering, L. Eckardt, M. Kuhlmann, N. Proskynitopoulos, J. Brunn, K. Foth, C. Axthelm, H. Hohensee, K. Eberhard, S. Turbanisch, N. Hassler, A. Koestler, G. Stenzel, D. Kschiwan, M. Schwefer, S. Neiner, S. Hettwer, M. Haeussler-Schuchardt, R. Degenhardt, S. Sennhenn, M. Brendel, A. Stoehr, W. Widjaja, S. Loehndorf, A. Logemann, J. Hoskamp, J. Grundt, M. Block, R. Ulrych, A. Reithmeier, V. Panagopoulos, C. Martignani, D. Bernucci, E. Fantecchi, I. Diemberger, M. Ziacchi, M. Biffi, P. Cimaglia, J. Frisoni, I. Giannini, S. Boni, S. Fumagalli, S. Pupo, A. Di Chiara, P. Mirone, F. Pesce, C. Zoccali, V.L. Malavasi, A. Mussagaliyeva, B. Ahyt, Z. Salihova, K. Koshum-Bayeva, A. Kerimkulova, A. Bairamukova, B. Lurina, R. Zuzans, S. Jegere, I. Mintale, K. Kupics, K. Jubele, O. Kalejs, K. Vanhear, M. Burg, M. Cachia, E. Abela, S. Warwicker, T. Tabone, R. Xuereb, D. Asanovic, D. Drakalovic, M. Vukmirovic, N. Pavlovic, L. Music, N. Bulatovic, A. Boskovic, H. Uiterwaal, N. Bijsterveld, J. De Groot, J. Neefs, N. van den Berg, F. Piersma, A. Wilde, V. Hagens, J. Van Es, J. Van Opstal, B. Van Rennes, H. Verheij, W. Breukers, G. Tjeerdsma, R. Nijmeijer, D. Wegink, R. Binnema, S. Said, S. Philippens, W. van Doorn, T. Szili-Torok, R. Bhagwandien, P. Janse, A. Muskens, M. van Eck, R. Gevers, N. van der Ven, A. Duygun, B. Rahel, J. Meeder, A. Vold, C. Holst Hansen, I. Engset, B. Dyduch-Fejklowicz, E. Koba, M. Cichocka, A. Sokal, A. Kubicius, E. Pruchniewicz, A. Kowalik-Sztylc, W. Czapla, I. Mróz, M. Kozlowski, T. Pawlowski, M. Tendera, A. Winiarska-Filipek, A. Fidyk, A. Slowikowski, M. Haberka, M. Lachor-Broda, M. Biedron, Z. Gasior, M. Kołodziej, M. Janion, I. Gorczyca-Michta, B. Wozakowska-Kaplon, M. Stasiak, P. Jakubowski, T. Ciurus, J. Drozdz, M. Simiera, P. Zajac, T. Wcislo, P. Zycinski, J. Kasprzak, A. Olejnik, E. Harc-Dyl, J. Miarka, M. Pasieka, M. Ziemińska-Łuć, W. Bujak, A. Śliwiński, A. Grech, J. Morka, K. Petrykowska, M. Prasał, G. Hordyński, P. Feusette, P. Lipski, A. Wester, W. Streb, J. Romanek, P. Woźniak, M. Chlebuś, P. Szafarz, W. Stanik, M. Zakrzewski, J. Kaźmierczak, A. Przybylska, E. Skorek, H. Błaszczyk, M. Stępień, S. Szabowski, W. Krysiak, M. Szymańska, J. Karasiński, J. Blicharz, M. Skura, K. Hałas, L. Michalczyk, Z. Orski, K. Krzyżanowski, A. Skrobowski, L. Zieliński, M. Tomaszewska-Kiecana, M. Dłużniewski, M. Kiliszek, M. Peller, M. Budnik, P. Balsam, G. Opolski, A. Tymińska, K. Ozierański, A. Wancerz, A. Borowiec, E. Majos, R. Dabrowski, H. Szwed, A. Musialik-Lydka, A. Leopold-Jadczyk, E. Jedrzejczyk-Patej, M. Koziel, M. Mazurek, K. Krzemien-Wolska, P. Starosta, E. Nowalany-Kozielska, A. Orzechowska, M. Szpot, M. Staszel, S. Almeida, H. Pereira, L. Brandão Alves, R. Miranda, L. Ribeiro, F. Costa, F. Morgado, P. Carmo, P. Galvao Santos, R. Bernardo, P. Adragão, G. Ferreira da Silva, M. Peres, M. Alves, M. Leal, A. Cordeiro, P. Magalhães, P. Fontes, S. Leão, A. Delgado, A. Costa, B. Marmelo, B. Rodrigues, D. Moreira, J. Santos, L. Santos, A. Terchet, D. Darabantiu, S. Mercea, V. Turcin Halka, A. Pop Moldovan, A. Gabor, B. Doka, G. Catanescu, H. Rus, L. Oboroceanu, E. Bobescu, R. Popescu, A. Dan, A. Buzea, I. Daha, G. Dan, I. Neuhoff, M. Baluta, R. Ploesteanu, N. Dumitrache, M. Vintila, A. Daraban, C. Japie, E. Badila, H. Tewelde, M. Hostiuc, S. Frunza, E. Tintea, D. Bartos, A. Ciobanu, I. Popescu, N. Toma, C. Gherghinescu, D. Cretu, N. Patrascu, C. Stoicescu, C. Udroiu, G. Bicescu, V. Vintila, D. Vinereanu, M. Cinteza, R. Rimbas, M. Grecu, A. Cozma, F. Boros, M. Ille, O. Tica, R. Tor, A. Corina, A. Jeewooth, B. Maria, C. Georgiana, C. Natalia, D. Alin, D. Dinu-Andrei, M. Livia, R. Daniela, R. Larisa, S. Umaar, T. Tamara, M. Ioachim Popescu, D. Nistor, I. Sus, O. Coborosanu, N. Alina-Ramona, R. Dan, L. Petrescu, G. Ionescu, C. Vacarescu, E. Goanta, M. Mangea, A. Ionac, C. Mornos, D. Cozma, S. Pescariu, E. Solodovnicova, I. Soldatova, J. Shutova, L. Tjuleneva, T. Zubova, V. Uskov, D. Obukhov, G. Rusanova, N. Isakova, S. Odinsova, T. Arhipova, E. Kazakevich, O. Zavyalova, T. Novikova, I. Riabaia, S. Zhigalov, E. Drozdova, I. Luchkina, Y. Monogarova, D. Hegya, L. Rodionova, V. Nevzorova, O. Lusanova, A. Arandjelovic, D. Toncev, L. Vukmirovic, M. Radisavljevic, M. Milanov, N. Sekularac, M. Zdravkovic, S. Hinic, S. Dimkovic, T. Acimovic, J. Saric, S. Radovanovic, A. Kocijancic, B. Obrenovic-Kircanski, D. Kalimanovska Ostric, D. Simic, I. Jovanovic, I. Petrovic, M. Polovina, M. Vukicevic, M. Tomasevic, N. Mujovic, N. Radivojevic, O. Petrovic, S. Aleksandric, V. Kovacevic, Z. Mijatovic, B. Ivanovic, M. Tesic, A. Ristic, B. Vujisic-Tesic, M. Nedeljkovic, A. Karadzic, A. Uscumlic, M. Prodanovic, M. Zlatar, M. Asanin, B. Bisenic, V. Vasic, Z. Popovic, D. Djikic, M. Sipic, V. Peric, B. Dejanovic, N. Milosevic, S. Backovic, A. Stevanovic, A. Andric, B. Pencic, M. Pavlovic-Kleut, V. Celic, M. Pavlovic, M. Petrovic, M. Vuleta, N. Petrovic, S. Simovic, Z. Savovic, S. Milanov, G. Davidovic, V. Iric-Cupic, D. Djordjevic, M. Damjanovic, S. Zdravkovic, V. Topic, D. Stanojevic, M. Randjelovic, R. Jankovic-Tomasevic, V. Atanaskovic, S. Antic, D. Simonovic, M. Stojanovic, S. Stojanovic, V. Mitic, V. Ilic, D. Petrovic, M. Deljanin Ilic, S. Ilic, V. Stoickov, S. Markovic, A. Mijatovic, D. Tanasic, G. Radakovic, J. Peranovic, N. Panic-Jelic, O. Vujadinovic, P. Pajic, S. Bekic, S. Kovacevic, A. García Fernandez, A. Perez Cabeza, M. Anguita, L. Tercedor Sanchez, E. Mau, J. Loayssa, M. Ayarra, M. Carpintero, I. Roldán Rabadan, M. Gil Ortega, A. Tello Montoliu, E. Orenes Piñero, S. Manzano Fernández, F. Marín, A. Romero Aniorte, A. Veliz Martínez, M. Quintana Giner, G. Ballesteros, M. Palacio, O. Alcalde, I. García-Bolao, V. Bertomeu Gonzalez, F. Otero-Raviña, J. García Seara, J. Gonzalez Juanatey, N. Dayal, P. Maziarski, P. Gentil-Baron, M. Koç, E. Onrat, I.E. Dural, K. Yilmaz, B. Özin, S. Tan Kurklu, Y. Atmaca, U. Canpolat, L. Tokgozoglu, A.K. Dolu, B. Demirtas, D. Sahin, O. Ozcan Celebi, G. Gagirci, U.O. Turk, H. Ari, N. Polat, N. Toprak, M. Sucu, O. Akin Serdar, A. Taha Alper, A. Kepez, Y. Yuksel, A. Uzunselvi, S. Yuksel, M. Sahin, O. Kayapinar, T. Ozcan, H. Kaya, M.B. Yilmaz, M. Kutlu, M. Demir, C. Gibbs, S. Kaminskiene, M. Bryce, A. Skinner, G. Belcher, J. Hunt, L. Stancombe, B. Holbrook, C. Peters, S. Tettersell, A. Shantsila, D. Lane, K. Senoo, M. Proietti, K. Russell, P. Domingos, S. Hussain, J. Partridge, R. Haynes, S. Bahadur, R. Brown, S. McMahon, J. McDonald, K. Balachandran, R. Singh, S. Garg, H. Desai, K. Davies, W. Goddard, G. Galasko, I. Rahman, Y. Chua, O. Payne, S. Preston, O. Brennan, L. Pedley, C. Whiteside, C. Dickinson, J. Brown, K. Jones, L. Benham, R. Brady, L. Buchanan, A. Ashton, H. Crowther, H. Fairlamb, S. Thornthwaite, C. Relph, A. McSkeane, U. Poultney, N. Kelsall, P. Rice, T. Wilson, M. Wrigley, R. Kaba, T. Patel, E. Young, J. Law, C. Runnett, H. Thomas, H. McKie, J. Fuller, S. Pick, A. Sharp, A. Hunt, K. Thorpe, C. Hardman, E. Cusack, L. Adams, M. Hough, S. Keenan, A. Bowring, J. Watts, J. Zaman, K. Goffin, H. Nutt, Y. Beerachee, J. Featherstone, C. Mills, J. Pearson, L. Stephenson, S. Grant, A. Wilson, C. Hawksworth, I. Alam, M. Robinson, S. Ryan, R. Egdell, E. Gibson, M. Holland, D. Leonard, B. Mishra, S. Ahmad, H. Randall, J. Hill, L. Reid, M. George, S. McKinley, L. Brockway, W. Milligan, J. Sobolewska, J. Muir, L. Tuckis, L. Winstanley, P. Jacob, S. Kaye, L. Morby, A. Jan, T. Sewell, C. Boos, B. Wadams, C. Cope, P. Jefferey, N. Andrews, A. Getty, A. Suttling, C. Turner, K. Hudson, R. Austin, S. Howe, R. Iqbal, N. Gandhi, K. Brophy, P. Mirza, E. Willard, S. Collins, N. Ndlovu, E. Subkovas, V. Karthikeyan, L. Waggett, A. Wood, A. Bolger, J. Stockport, L. Evans, E. Harman, J. Starling, L. Williams, V. Saul, M. Sinha, L. Bell, S. Tudgay, S. Kemp, L. Frost, T. Ingram, A. Loughlin, C. Adams, M. Adams, F. Hurford, C. Owen, C. Miller, D. Donaldson, H. Tivenan, H. Button, A. Nasser, O. Jhagra, B. Stidolph, C. Brown, C. Livingstone, M. Duffy, P. Madgwick, P. Roberts, E. Greenwood, L. Fletcher, M. Beveridge, S. Earles, D. McKenzie, D. Beacock, M. Dayer, M. Seddon, D. Greenwell, F. Luxton, F. Venn, H. Mills, J. Rewbury, K. James, K. Roberts, L. Tonks, D. Felmeden, W. Taggu, A. Summerhayes, D. Hughes, J. Sutton, L. Felmeden, M. Khan, E. Walker, L. Norris, L. O'Donohoe, A. Mozid, H. Dymond, H. Lloyd-Jones, G. Saunders, D. Simmons, D. Coles, D. Cotterill, S. Beech, S. Kidd, B. Wrigley, S. Petkar, A. Smallwood, R. Jones, E. Radford, S. Milgate, S. Metherell, V. Cottam, C. Buckley, A. Broadley, D. Wood, J. Allison, K. Rennie, L. Balian, L. Howard, L. Pippard, S. Board, and T. Pitt-Kerby

Subjects
Male, AF registry, Atrial fibrillation, Biomarkers, Death, Major adverse cardiovascular events, outcomes, Troponins, Troponin, Risk Factors, Atrial Fibrillation, Internal Medicine, Humans, Female, Prospective Studies, Registries, Aged
Abstract

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Published
2022
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50. Associations between Domestic-Dog Morphology and Behaviour Scores in the Dog Mentality Assessment.

Author

Holly R Stone, Paul D McGreevy, Melissa J Starling, and Bjorn Forkman

Subjects
Medicine, Science
Abstract

The domestic dog shows a wide range of morphologies, that humans have selected for in the process of creating unique breeds. Recent studies have revealed correlations between changes in morphology and behaviour as reported by owners. For example, as height and weight decrease, many undesirable behaviours (non-social fear, hyperactivity and attention seeking) become more apparent. The current study aimed to explore more of these correlations, but this time used reports from trained observers. Phenotypic measurements were recorded from a range of common dog breeds (n = 45) and included cephalic index (CI: the ratio of skull width to skull length), bodyweight, height and sex. These data were then correlated with results from the Dog Mentality Assessment (DMA), which involves trained observers scoring a dog's reaction to stimuli presented over 10 standardised subtests. Each subtest is designed to evoke a behavioural response. Backward elimination and weighted step-wise regression revealed that shorter dogs demonstrated more aggressive tendencies, reacting defensively toward both assistants dressed as ghosts (p = 0.045), and to a dummy (p = 0.008). Taller dogs were more affectionate when greeting and being handled by humans (p = 0.007, p =

Published
2016
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