Author: "H., Stone" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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1,392 results on '"H., Stone"'

1. Acute exacerbations in patients with progressive pulmonary fibrosis

Author: Michael Kreuter, Elizabeth A. Belloli, Elisabeth Bendstrup, Stefania Cerri, Kevin R. Flaherty, Shane Shapera, Jin Woo Song, Heiko Mueller, Klaus B. Rohr, Yasuhiro Kondoh, on behalf of the INBUILD trial investigators, S. Quadrelli, M. Otaola, M.A. Bergna, P. Elias, G. Arce, A. Cazaux, J. Guiot, B. Bondue, C. Dahlqvist, L. Homik, S. Shapera, A. Cantin, M. Kolb, M. Salinas Fénero, R. Maturana Rozas, A. Silva Orellana, Z. Xu, Q. Luo, J. Kang, H. Cai, S. Marchand-Adam, E. Bergot, A. Gamez-Dubuis, F. Riviere, R. Kessler, H. Nunes, C. Marquette, L. Wemeau, S. Jouneau, F. Lebargy, B. Crestani, V. Cottin, M. Reynaud-Gaubert, S. Blaas, F. Bonella, W. Randerath, J. Hetzel, D. Koschel, M. Kreuter, A. Prasse, D. Skowasch, S. Stieglitz, R. Refini, S. Cerri, A. Pesci, S. Tomassetti, C. Vancheri, F. Varone, N. Sakamoto, S. Abe, H. Hayashi, T. Saito, T. Suda, H. Kitamura, M. Okamoto, Y. Kondoh, S. Makino, T. Takeuchi, Y. Yamada, C. Kono, Y. Inoue, H. Sugiura, K. Kishi, H. Takaya, H. Yamauchi, K. Ichikado, K. Tomii, H. Takahashi, S. Izumi, T. Kawamura, Y. Nishioka, Y. Miyazaki, J.W. Song, J.S. Park, Y. Kim, E. Jassem, J. Kus, W. Piotrowski, A. Barczyk, D. Ziora, E. Bazdyrev, S. Moiseev, S. Avdeev, M. Ilkovich, V. Yakusevich, C. Valenzuela, O. Acosta, M. Martínez, L. Gómez, M. Molina-Molina, D.M. Castillo Villegas, M. Aburto, J.A. Rodríguez Portal, A. Villar, A. León Jiménez, J. Sauleda, M. Arias, P. Beirne, H. Stone, B. Hope-Gill, N. Hirani, N. Chaudhuri, A. Gifford, L. Jones, L. Morrison, D. Antin-Ozerkis, N. Bhatt, T. Kulkarni, T. Moua, N. Ettinger, L. Pitts, S. Veeraraghavan, M. Padilla, E.R. Fernández Pérez, G. Giessel, M. Strek, S. Danoff, J. Burk, M. Rossman, N. Patel, E. Belloli, D. Hotchkin, S. Weigt, M.B. Scholand, R. Kaner, B. Sigal, Z. Safdar, L. Tolle, R. Martinez, M. Glassberg, R. Hallowell, J. Golden, M. Schwartz, E. Britt, L. Morrow, Y. Mageto, K. Buch, S. Chaaban, H. Poonyagariyagorn, D. Dilling, O. Shlobin, K. Thavarajah, A. Nambiar, I. Rosas, R. Bascom, J. Oldham, S. Schmidt, J. Dematte D'Amico, J. Falk, C. Glazer, and G. Criner
Subjects: Medicine
Abstract: Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Methods Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan−Meier method. Results Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, treatment and age. Lower DLCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21–2.02) per 10 units lower (p
Published: 2024
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2. Sap flow of sweet cherry reveals distinct effects of humidity and wind under rain covered and netted protected cropping systems

Author: C. H. Stone, D. C. Close, R. Corkrey, and I. Goodwin
Subjects: Medicine, Science
Abstract: Abstract Protected cropping systems (PCS) alter the plant growing environment, though understanding of this in ventilated systems and how the new climate affects tree water uptake is limited. Sap flow sensors and weather stations were deployed in 16-year-old ‘Lapins’ on ‘Colt’ rootstock cherry trees under a ventilated Voen PCS and in an adjacent bird netted PCS. Average and maximum temperatures were consistently higher (14.7 °C and 22.9 °C) while total daily solar radiation and average wind were consistently lower (12.9 MJ/m2 and 0.2 m/s) in rain covered, in contrast to netted, PCS (13.9 °C, 21.3 °C, 13.7 MJ/m2 and 0.9 m/s). Over the season, a threefold lower daily sap flow rate was observed under rain covered PCS. Using generalised additive modelling (GAM), the influence of individual climate parameters on sap flow were predicted. Whilst sap flow was only slightly affected by relative humidity (RH) less than 60%, above this threshold sap flow rapidly declined under rain covered PCS whereas sap flow more gradually declined above 20% RH under netted PCS. Overall, our novel modelling approach led to the discovery of the 60% RH critical threshold on predicted sap flow and the indirect effect that wind speeds have on sap flow under PCS.
Published: 2022
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3. Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome

Author: Naoki Kaneko, Hu Chen, Cory A. Perugino, Takashi Maehara, Ryusuke Munemura, Shiho Yokomizo, Junsei Sameshima, Thomas J. Diefenbach, Katherine R. Premo, Akira Chinju, Yuka Miyahara, Mizuki Sakamoto, Masafumi Moriyama, John H. Stone, Seiji Nakamura, and Shiv Pillai
Subjects: Medicine, Science
Abstract: Abstract Sjögren’s syndrome is a chronic autoimmune disorder whose pathogenesis is poorly understood and that lacks effective therapies. Detailed quantitative and spatial analyses of tissues affected by Sjögren’s syndrome were undertaken, including the quantitation of the frequency of selected cell–cell interactions in the disease milieu. Quantitative analyses of CD4+ T cell subsets and of CD8+ T cells in the labial salivary glands from untreated patients with primary Sjögren’s syndrome revealed that activated CD8+ cytotoxic T cells (CD8+CTLs) were the most prominent T cells in these infiltrates. An accumulation of apoptotic glandular epithelial cells, mainly ductal and acinar cells, was observed, consistent with the impaired salivary secretion often observed in patients with this disease. FasL expressing activated CD8+ T cells were seen to accumulate around Fas expressing apoptotic epithelial cells. Quantitative analyses of apoptotic cell types and of conjugates between cytotoxic T cells and epithelial cells undergoing apoptosis suggest that Sjögren’s syndrome is primarily driven by CD8+CTL mediated execution of epithelial cells mainly represented by ductal and acinar cells.
Published: 2022
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4. Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK

Author: William Waites, Carl A. B. Pearson, Katherine M. Gaskell, Thomas House, Lorenzo Pellis, Marina Johnson, Victoria Gould, Adam Hunt, Neil R. H. Stone, Ben Kasstan, Tracey Chantler, Sham Lal, Chrissy H. Roberts, David Goldblatt, CMMID COVID-19 Working Group, Michael Marks, and Rosalind M. Eggo
Subjects: Medicine, Science
Abstract: Abstract Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.
Published: 2022
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5. Barriers to and facilitators of hormonal and long-acting reversible contraception access and use in the US among reproductive-aged women who use opioids: A scoping review

Author: Elizabeth Charron, Jacqueline Kent-Marvick, Tyler Gibson, Eliza Taylor, Kelsey Bouwman, Gelina M. Sani, Sara E. Simonsen, Rebecca H. Stone, Jennifer E. Kaiser, and Mary M. McFarland
Subjects: Hormonal contraception, Long-acting reversible contraception, Contraceptive access, Opioids, Opioid use, Opioid use disorder, Medicine
Abstract: Existing research has found that women who use opioids (WWUO) experience challenges to hormonal and long-acting reversible contraception (HC-LARC) access and use. Facilitators of such use are unclear. We conducted a scoping review to comprehensively map the literature on barriers to and facilitators of HC-LARC access and use in the United States among reproductive-aged WWUO. In accordance with the JBI Manual of Evidence Synthesis, we conducted literature searches for empirical articles published from 1990 to 2021. Independent reviewers screened references, first by titles and abstracts, then by full-text, and charted data of eligible articles. We coded and organized HC-LARC barriers and facilitators according to a four-level social-ecological model (SEM) and categorized findings within each SEM level into domains. We screened 4,617 records, of which 28 articles focusing on HC-LARC (n = 18), LARC only (n = 6), or testing an intervention to increase HC-LARC uptake (n = 4) met inclusion criteria. We identified 13 domains of barriers and 11 domains of facilitators across four SEM levels (individual, relationship, community, societal). The most frequently cited barriers and facilitators were methods characteristics, partner and provider relations, transportation, healthcare availability and accessibility, cost, insurance, and stigma. Future studies would benefit from recruiting participants and collecting data in community settings, targeting more diverse populations, and identifying neighborhood, social, and policy barriers and facilitators. Reducing barriers and improving equity in HC-LARC access and use among WWUO is a complex, multifaceted issue that will require targeting factors simultaneously at multiple levels of the social-ecological hierarchy to effect change.
Published: 2023
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6. Risk of relapse of ANCA-associated vasculitis among patients homozygous for the proteinase 3 gene Val119Ile polymorphism

Author: John H Stone, Peter C Grayson, Ulrich Specks, E William St Clair, Peter A Merkel, Philip Seo, Carol A Langford, Paul A Monach, Cees G M Kallenberg, Robert F Spiera, Fernando C Fervenza, Zuoming Deng, Wei Tew, Marta Casal Moura, Stephen R Brooks, and Marco Prunotto
Subjects: Medicine
Abstract: Background The frequency of proteinase 3 gene (PRTN3) polymorphisms in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not fully characterised. We hypothesise that the presence of a PRTN3 gene polymorphism (single nucleotide polymorphism (SNP) rs351111) is relevant for clinical outcomes.Methods DNA variant calling for SNP rs351111 (chr.19:844020, c.355G>A) in PRTN3 gene assessed the allelic frequency in patients with PR3-AAV included in the Rituximab in ANCA-Associated Vasculitis trial. This was followed by RNA-seq variant calling to characterise the mRNA expression. We compared clinical outcomes between patients homozygous for PRTN3-Ile119 or PRTN3-Val119.Results Whole blood samples for DNA calling were available in 188 patients. 75 patients with PR3-AAV had the allelic variant: 62 heterozygous PRTN3-Val119Ile and 13 homozygous for PRTN3-Ile119. RNA-seq was available for 89 patients and mRNA corresponding to the allelic variant was found in 32 patients with PR3-AAV: 25 heterozygous PRTN3-Val119Ile and 7 homozygous for PRTN3-Ile119. The agreement between the DNA calling results and mRNA expression of the 86 patients analysed by both methods was 100%. We compared the clinical outcomes of 64 patients with PR3-AAV: 51 homozygous for PRTN3-Val119 and 13 homozygous for PRTN3-Ile119. The frequency of severe flares at 18 months in homozygous PRTN3-Ile119 was significantly higher when compared with homozygous PRTN3-Val119 (46.2% vs 19.6%, p=0.048). Multivariate analysis identified homozygous PR3-Ile119 as main predictor of severe relapse (HR 4.67, 95% CI 1.16 to 18.86, p=0.030).Conclusion In patients with PR3-AAV, homozygosity for PRTN3-Val119Ile polymorphism appears associated with higher frequency of severe relapse. Further studies are necessary to better understand the association of this observation with the risk of severe relapse.
Published: 2023
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7. Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis

Author: Damian R. Plichta, Juhi Somani, Matthieu Pichaud, Zachary S. Wallace, Ana D. Fernandes, Cory A. Perugino, Harri Lähdesmäki, John H. Stone, Hera Vlamakis, Daniel C. Chung, Dinesh Khanna, Shiv Pillai, and Ramnik J. Xavier
Subjects: Gut microbiome, IgG4-RD, Systemic sclerosis, Autoimmunity, Medicine, Genetics, QH426-470
Abstract: Abstract Background Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors. Methods The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases. Results Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism. Conclusions These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.
Published: 2021
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8. Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis

Author: Alvise Berti, Sophie Hillion, Amber M. Hummel, Young Min Son, Nedra Chriti, Tobias Peikert, Eva M. Carmona, Wayel H. Abdulahad, Peter Heeringa, Kristina M. Harris, E. William St. Clair, Paul Brunetta, Fernando C. Fervenza, Carol A. Langford, Cees G.M. Kallenberg, Peter A. Merkel, Paul A. Monach, Philip Seo, Robert F. Spiera, John H. Stone, Guido Grandi, Jie Sun, Jacques-Olivier Pers, Ulrich Specks, Divi Cornec, and for the RAVE-ITN Research Group
Subjects: Autoimmunity, Immunology, Medicine
Abstract: BACKGROUND Little is known about the autoreactive B cells in antineutrophil cytoplasmic antibody–associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3–reactive (PR3+) B cells.METHODS Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets).RESULTS The frequency of PR3+ B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%–6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%–5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%–2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3+ B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001).CONCLUSION This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells.Trial registration ClinicalTrials.gov NCT00104299.Funding The Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research.
Published: 2021
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9. LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling

Author: Viorel Simion, Haoyang Zhou, Jacob B. Pierce, Dafeng Yang, Stefan Haemmig, Yevgenia Tesmenitsky, Galina Sukhova, Peter H. Stone, Peter Libby, and Mark W. Feinberg
Subjects: Vascular biology, Medicine
Abstract: Long noncoding RNAs (lncRNAs) play important roles in regulating diverse cellular processes in the vessel wall, including atherosclerosis. RNA-Seq profiling of intimal lesions revealed a lncRNA, VINAS (Vascular INflammation and Atherosclerosis lncRNA Sequence), that is enriched in the aortic intima and regulates vascular inflammation. Aortic intimal expression of VINAS fell with atherosclerotic progression and rose with regression. VINAS knockdown reduced atherosclerotic lesion formation by 55% in LDL receptor–deficient (LDLR–/–) mice, independent of effects on circulating lipids, by decreasing inflammation in the vessel wall. Loss- and gain-of-function studies in vitro demonstrated that VINAS serves as a critical regulator of inflammation by modulating NF-κB and MAPK signaling pathways. VINAS knockdown decreased the expression of key inflammatory markers, such as MCP-1, TNF-α, IL-1β, and COX-2, in endothelial cells (ECs), vascular smooth muscle cells, and bone marrow–derived macrophages. Moreover, VINAS silencing decreased expression of leukocyte adhesion molecules VCAM-1, E-selectin, and ICAM-1 and reduced monocyte adhesion to ECs. DEP domain containing 4 (DEPDC4), an evolutionary conserved human ortholog of VINAS with approximately 74% homology, showed similar regulation in human and pig atherosclerotic specimens. DEPDC4 knockdown replicated antiinflammatory effects of VINAS in human ECs. These findings reveal a potentially novel lncRNA that regulates vascular inflammation, with broad implications for vascular diseases.
Published: 2020
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10. Feasibility of reporting results of large randomised controlled trials to participants: experience from the Fluoxetine Or Control Under Supervision (FOCUS) trial

Author: Martin Dennis, D Cohen, A Thompson, M Smith, A Naqvi, Graham Ellis, A Khan, L Hunt, X Huang, J Andrews, J Foot, J Smith, S Wong, A Stevens, D Bailey, S Johnston, S Jones, R Robinson, A Johnson, S Williams, T Smith, A Ahmed, S Bloom, L Sekaran, D Singh, F Smith, R Greenwood, A Singh, R Brown, J White, S Smith, S Arif, S Ross, S Trippier, S Levy, B Patel, M Khan, A Thomas, S Brown, V Jones, D Wood, S Maguire, U Khan, P Nair, A Smith, G Hann, R Williams, M Cooper, S Jackson, M Hassan, P Kumar, A Metcalf, R Patel, A Wright, S Khan, A Bell, C Williams, M Robinson, K Jones, S Alam, R Shah, J Simpson, K Ali, K Miller, K Kennedy, S Ahmed, J Francis, L Thomas, M Scott, S Nelson, S Clayton, L Zhang, B Charles, P Lopez, A Fleming, C Lambert, A Shah, J Wong, David Burgess, L Wilson, A Siddiqui, S Kumar, A Hassan, D Cooke, M Williams, P Cooper, S Graham, S Morrison, M Holland, C Green, C Edwards, K Subramanian, K Patel, J Mitchell, J Stewart, S Keenan, C Duggan, S McKenna, R Murphy, M Ward, S Walker, S Lewis, R Jones, L Wright, M Edwards, N Sattar, J Mcgee, R Butler, M Wilkinson, S Das, C Kelly, R Cowan, C Brown, K Moore, L Denny, M Harrison, S Patel, R Rodriguez, J Allen, M Kalita, Gillian Mead, A Bowring, A Edwards, J Scott, J Drew, D Ward, L Dixon, K Burton, E Brown, E Epstein, R Miller, F Reid, A Jones, P Murphy, A Ali, N Ahmad, S Noor, C Leonard, A Nair, M Naeem, M Johnson, E Douglas, J Thompson, R Evans, C Jenkins, J Wilson, R Anderson, H Wilson, H Stone, J Ward, L Greenhalgh, P Walker, A Hill, K Stagg, S Naqvi, R Scott, M Hughes, P Jones, M Simpson, K Elliott, M Davy, S Young, Karen Innes, Pippa Tyrrell, A David, Steff Lewis, A Bwalya, C Buckley, S Kelly, C Thomas, I Kane, M Hussain, S Shah, J Roberts, D Morales, C McInnes, N Khan, N Weir, L Hill, J McLaughlin, K Kavanagh, R Clarke, P Thompson, J Price, J Ball, L Benton, E Walton, E Walker, L Burgess, K McCormick, L Wade, C Anderson, S Stevenson, R Blackburn, L Brown, B Clarke, T Khan, S Dhar, L Harrison, S Bell, D Buchanan, A Deary, J Drever, R Fraser, C Graham, K Innes, C McGill, D Perry, A Barugh, G Blair, Y Chun, E Maschauer, J Forbes, M Hackett, G Hankey, A House, E Lundström, Peter Sandercock, Judith Williamson, John Forbes, Graeme Hankey, Maree Hackett, Veronica Murray, Ray French, David Stott, Jonathan Emberson, P Sandercock, M MacLeod, F Sullivan, P Langhorne, H Rodgers, N Hunter, R Parakramawansha, A Fazal, P Taylor, W Rutherford, R Buchan, A MacRaild, R Paulton, S Burgess, D McGowan, J Skwarski, F Proudfoot, J Perry, J Bamford, C Bedford, D Waugh, E Veraque, M Kambafwile, L Makawa, P Smalley, M Randall, L Idrovo, T Thirugnana-Chandran, R Vowden, J Jackson, A Bhalla, C Tam, A Rudd, C Gibbs, J Birns, L Lee Carbon, E Cattermole, A Cape, L hurley, K Marks, S Kullane, N Smyth, E Giallombardo, C Eglinton, D Dellafera, P Reidy, M Pitt, L Sykes, A Frith, V Croome, J Duffy, M Hancevic, L Kerwood, C Narh, C Merritt, J Willson, T Jackson, H Bowler, C Kamara, J Howe, K Stocks, G Dunn, K Endean, F Claydon, S Duty, C Doyle, K Harkness, E Richards, M Meegada, A Maatouk, L Barron, K Dakin, R Lindert, A Majid, P Rana, C Brighouse-Johnson, J Greig, M Kyu, S Prasad, B Mclean, I Alam, Z Ahmed, C Roffe, S Brammer, A Barry, C Beardmore, K Finney, H Maguire, P Hollinshead, J Grocott, I Natarajan, J Chembala, R Sanyal, S Lijko, N Abano, A Remegoso, P Ferdinand, S Stevens, C Stephen, P Whitmore, A Butler, C Causley, R Varquez, G Muddegowda, R Carpio, J Hiden, H Denic, J Sword, F Hall, J Cageao, R Curwen, M James, P Mudd, C Roughan, H Kingwell, A Hemsley, C Lohan, S Davenport, T Chapter, M Hough, D Strain, K Gupwell, A Goff, E Cusack, S Todd, R Partridge, G Jennings, K Thorpe, J Stephenson, K Littlewood, M Barber, F Brodie, S Marshall, D Esson, I Coburn, F Ross, V Withers, E Bowie, H Barcroft, L Miller, P Willcoxson, M Keeling, M Donninson, D Daniel, J Coyle, M Elliott, P Wanklyn, J Wightman, E Iveson, A Porteous, N Dyer, M Haritakis, J Bell, C Emms, P Wood, P Cottrell, L Doughty, L Carr, C Anazodo, M O Neill, J Westmoreland, R Mir, C Donne, E Bamford, P Clark Brown, A Stanners, I Ghouri, A Needle, M Eastwood, M Carpenter, P Datta, R Davey, F Razik, G Bateman, J Archer, V Balasubramanian, L Jackson, R Bowers, J Ellam, K Norton, P Guyler, S Tysoe, P Harman, A Kundu, T Dowling, S Chandler, O Omodunbi, T Loganathan, S Kunhunny, D Sinha, M Sheppard, S Kelavkar, K Ng, A Ropun, L Kamuriwo, R Orath Prabakaran, E France, S Rashmi, D Mangion, C Constantin, S Markova, A Hardwick, J Borley, L De Michele Hock, T Lawrence, J Fletcher, K Netherton, R Spencer, H Palmer, M Soliman, S Leach, J Sharma, C Taylor, I Wahishi, A Fields, S Butler, J Hindle, E Watson, C Hewitt, C Cullen, D Hamill, Z Mellor, T Fluskey, V Hankin, A Keeling, R Durairaj, D Shackcloth, R Tangney, T Hlaing, V Sutton, J Ewing, C Patterson, H Ramadan, R Bellfield, U Hamid, M Hooley, R Ghulam, L Masters, W Gaba, O Quinn, M Tate, N Mohammed, S Sethuraman, L Alwis, K Bharaj, R Pattni, F Justin, M Chauhan, L Eldridge, S Mintias, J Palmones, C Holmes, L Guthrie, N Devitt, J Leonard, M Osborn, L Ball, A Steele, E Dodd, A Holloway, P Baker, I Penwarden, S Caine, S Clarke, L Dow, R Wynn-Williams, J Kennedy, A DeVeciana, P Mathieson, I Reckless, R Teal, U Schulz, G Ford, P Mccann, G Cluckie, G Howell, J Ayer, B Moynihan, R Ghatala, G Cloud, N Al-Samarrai, F Watson, T Adedoyin, N Chopra, L Choy, N Clarke, A Dainty, A Blight, J Selvarajah, W Smith, F Moreton, A Welch, D Kalladka, B Cheripelli, A Lush, S El Tawil, N Day, K Montgomery, H Hamilton, D Ritchie, S Ramachandra, K McLeish, B Badiani, M Abdul-Saheb, A Chamberlain, M Mpelembue, R Bathula, M Lang, J Devine, L Southworth, N Epie, E Owoyele, F Guo, A Oshodi, V Sudkeo, K Thavanesan, D Tiwari, C Ovington, E Rogers, R Bower, B Longland, O David, A Hogan, S Loganathan, C Cox, S Orr, M Keltos, K Rashed, B Williams-Yesson, J Board, S De Bruijn, C Vickers, S Board, J Allison, E Keeling, T Duckett, D Donaldson, C Barron, L Balian, T England, A Hedstrom, E Bedford, M Harper, E Melikyan, W Abbott, M Goldsworthy, M Srinivasan, I Mukherjee, U Ghani, A Yeomans, F Hurford, R Chapman, S Shahzad, N Motherwell, L Tonks, R Young, D Dutta, P Brown, F Davis, J Turfrey, M Obaid, B Cartwright, B Topia, J Spurway, C Hughes, S OConnell, K Collins, R Bakawala, K Chatterjee, T Webster, S Haider, P Rushworth, F Macleod, C Perkins, A Nallasivan, E Burns, S Leason, T Carter, S Seagrave, E Sami, S Parkinson, L Armstrong, S Mawer, G Darnbrook, C Booth, B Hairsine, S Williamson, F Farquhar, B Esisi, T Cassidy, B McClelland, G Mankin, M Bokhari, D Sproates, S Hurdowar, N Sukhdeep, S Razak, N Upton, A Hashmi, K Osman, K Fotherby, A Willberry, D Morgan, G Sahota, K Jennings-Preece, D Butler, K Kauldhar, F Harrington, A Mate, J Skewes, K Adie, K Bond, G Courtauld, C Schofield, L Lucas, A James, S Ellis, B Maund, L Allsop, C Brodie, E Driver, K Harris, M Drake, E Thomas, M Burn, A Hamilton, S Mahalingam, A Benford, D Hilton, A Misra, L Hazell, K Ofori, M Mathew, S Dayal, I Burn, D Bruce, R Burnip, R Hayman, P Earnshaw, P Gamble, S Dima, M Dhakal, G Rogers, L Stephenson, R Nendick, Y Pai, K Nyo, V Cvoro, M Couser, A Tachtatzis, K Ullah, R Cain, N Chapman, S Pound, S McAuley, D Hargroves, B Ransom, K Mears, K Griffiths, L Cowie, T Hammond, T Webb, I Balogun, H Rudenko, A Thomson, D Ceccarelli, A Gillian, E Beranova, A Verrion, N Chattha, N Schumacher, A Bahk, D Sims, R Tongue, M Willmot, C Sutton, E Littleton, J Khaira, S Maiden, J Cunningham, Y Chin, M Bates, K Ahlquist, J Breeds, T Sargent, L Latter, A Pitt Ford, T Levett, N Gainsborough, A Dunne, E Barbon, S Hervey, S Ragab, T Sandell, C Dickson, S Power, J Dube, N Evans, B Wadams, S Elitova, B Aubrey, T Garcia, J Mcilmoyle, C Dickinson, C Jeffs, J Howard, C Armer, J Frudd, A Potter, S Donaldson, D Collas, S Sundayi, L Denham, D Oza, M Bhandari, S Ispoglou, K Sharobeem, A Hayes, J Howard-Brown, S Shanu, S Billingham, G Howard, E Wood, V Pressly, P Crawford, H Burton, A Walters, J Marigold, R Said, C Allen, S Evans, S Egerton, J Hakkak, R Lampard, S Tsang, R Creeden, I Gartrell, F Price, J Pryor, A Hedges, L Moseley, L Mercer, E Warburton, D Handley, S Finlay, N Hannon, A Espanol, H Markus, D Chandrasena, J Sesay, D Hayden, H Hayhoe, J Macdonald, M Bolton, C Farron, E Amis, D Day, A Culbert, L Whitehead, S Crisp, J OConnell, E Osborne, R Beard, P Corrigan, L Mokoena, M Myint, R Krishnamurthy, A Azim, S Whitworth, A Nicolson, M Krasinska-Chavez, J Imam, S Chaplin, J Curtis, L Wood, A Byrne, C McGhee, A Smart, F Donaldson, J Blackburn, C Copeland, P Fitzsimmons, G Fletcher, A Manoj, P Cox, L Trainor, H Allsop, U Sukys, S Valentine, D Jarrett, K Dodsworth, M Wands, C Watkinson, W Golding, J Tandy, K Yip, C James, Y Davies, A Suttling, K Nagaratnam, N Mannava, N Haque, N Shields, K Preston, G Mason, K Short, G Uitenbosch, G Lumsdale, H Emsley, S Sultan, B Walmsley, D Doyle, A McLoughlin, L Hough, B Gregary, S Raj, A Maney, S Blane, G Gamble, A Hague, B Duran, R Whiting, M Harvey, J Homan, L Foote, L Graham, C Lane, L Kemp, J Rowe, H Durman, L Brotherton, N Hunt, A Whitcher, C Pawley, P Sutton, S Mcdonald, D Pak, A Wiltshire, J Balami, C Self, J Jagger, G Healey, M Crofts, A Chakrabarti, C Hmu, J Keshet-Price, G Ravenhill, C Grimmer, T Soe, I Potter, P Tam, M Langley, M Christie, J Irvine, A Joyson, F Annison, D Christie, C Meneses, V Taylor, J Furnace, H Gow, J Reid, Y Abousleiman, S Goshawk, J Purcell, T Beadling, S Collins, S Sangaralingham, E Munuswamy Vaiyapuri, M Landicho, Y Begum, S Mutton, J Lowe, I Wiggam, S Tauro, S Cuddy, B Wells, A Mohd Nor, N Persad, M Weinling, S Weatherby, D Lashley, A Pace, A Mucha, J Baker, M Marner, J Westcott, N Wilmshurst, D Chadha, M Fairweather, D Walstow, R Fong, M Krishnan, H Thompson Jones, C Lynda, C Clements, T Anjum, S Sharon, D Lynne, S Tucker, D Colwill, E Vasileiadis, A Parry, C Mason, M Holden, K Petrides, T Nishiyama, H Mehta, S Mumani, C Almadenboyle, S Carson, M Stirling, E Tenbruck, D Broughton, A Annamalai, D Tryambake, A Skotnicka, A Sigsworth, S Whitehouse, J Pagan, A Pusalkar, H Beadle, K Chan, P Dangri, A Asokanathan, A Rana, S Gohil, K Crabtree, A Cook, M Massyn, P Aruldoss, S Dabbagh, T Black, C Clarke, R Fennelly, L Nardone, V DiMartino, A Anthony, D Mead, M Tribbeck, B Affley, C Sunderland, E Young, L Goldenberg, P Wilkinson, L Abbott, R Nari, S Lock, A Shakhon, R Pereira, M DSouza, S Dunn, N Cron, A Mckenna, R Sivakumar, S Cook, J Ngeh, R Saksena, J Ketley-O'Donel, R Needle, E Chinery, L Howaniec, C Watchurst, R Erande, M Brezitski, N Passeron, E Elliott, N Oji, D Austin, A Banaras, C Hogan, T Corbett, M Kidd, G Hull, S Punekar, J Nevinson, H Penney, W Wareing, N Hayes, K Bunworth, L Connell, K Mahawish, G Drummond, N Sengupta, M Metiu, C Gonzalez, J Margalef, S Funnell, G Peters, I Chadbourn, H Proeschel, P Ashcroft, S Sharpe, P Cook, D Jenkinson, D Kelly, H Bray, G Gunathilagan, S Tilbey, S Abubakar, A Rajapakse, A Nasar, J Janbieh, L Otter, I Wynter, S Haigh, R Boulton, J Burgoyne, A Boulton, J Vassallo, A Hasan, L Orrell, S Qamar, D Leonard, E Hewitt, M Haque, J Awolesi, E Bradshaw, A Kent, A Hynes, E Nurse, S Raza, U Pallikona, B Edwards, G Morgan, H Tench, R Loosley, K Dennett, T Trugeon-Smith, D Robson, R Rayessa, A Abdul-Hamid, V Lowthorpe, K Mitchelson, E Clarkson, H Rhian, R Kirthivasan, J Topliffe, R Keskeys, F McNeela, E Bohannan, L Cooper, G Zachariah, F Cairns, T James, L Fergey, S Smolen, A Lyle, E Cannon, S Omer, S Mavinamane, S Meenakshisundaram, L Ranga, J Bate, M Hargreaves, S Dealing, S Amlani, G Gulli, M Hawkes-Blackburn, L Francis, S Holland, A Peacocke, J Amero, M Burova, O Speirs, S Brotheridge, S Al Hussayni, H Lyon, C Hare, J Featherstone, M Goorah, J Walford, D Rusk, D Sutton, F Patel, S Duberley, K Hayes, E Ahmed El Nour, S Dyer, E Temlett, J Paterson, S Honour, C Box, R Furness, E Orugun, H Crowther, R Glover, C Brewer, S Thornthwaite, M Sein, K Haque, L Bailey, E Gibson, L Brookes, K Rotchell, K Waltho, C Lindley, P Harlekar, C Culmsee, L Booth, J Ritchie, N Mackenzie, J Barker, M Haley, D Cotterill, L Lane, D Simmons, R Warinton, G Saunders, H Dymond, S Kidd, C Little, Y Neves-Silva, B Nevajda, M Villaruel, U Umasankar, A Man, N Gadi, N Christmas, R Ladner, R Rangasamy, G Butt, W Alvares, M Power, S Hagan, K Dynan, D Wilson, S Crothers, B Wroath, G Douris, D Vahidassr, B Gallen, C McGoldrick, M Bhattad, J Putteril, R Gallifent, E Makanju, M Lepore, C McRedmond, L Arundell, A Goulding, K Kawafi, P Jacob, L Turner, N Saravanan, L Johnson, D Morse, R Namushi, S Humphrey, M Salehin, S Tinsley, T Jones, L Garcia-Alen, L Kalathil, N Gautam, J Horton, J Meir, E Margerum, A Ritchings, K Amor, V Nadarajan, J Laurence, S Fung Lo, S Melander, P Nicholas, E Woodford, G McKenzie, V Le, J Crause, P OMahony, C Orefo, C McDonald, E Osikominu, G Appiatse, A Wardale, M Augustin, R Luder, M Bhargava, G Bhome, V Johnson, D Chesser, H Bridger, E Murali, A Burns, J Graham, M Duffy, E Pitcher, J Gaylard, J Newman, S Punnoose, S Oakley, V Murray, C Bent, R Walker, K Purohit, A Rees, S Besley, O Chohan, L Argandona, L Cuenoud, H Hassan, E Erumere, A OCallaghan, O Redjep, G Auld, P Gompertz, A Song, R Hungwe, H Kabash, T Tarkas, G Livingstone, F Butler, S Bradfield, L Gordon, J Schmit, A Wijewardane, C Medcalf, T Edmunds, R Wills, and C Peixoto
Subjects: Medicine
Abstract: Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.
Published: 2020
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11. Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning.

Author: Lohendran Baskaran, Subhi J Al'Aref, Gabriel Maliakal, Benjamin C Lee, Zhuoran Xu, Jeong W Choi, Sang-Eun Lee, Ji Min Sung, Fay Y Lin, Simon Dunham, Bobak Mosadegh, Yong-Jin Kim, Ilan Gottlieb, Byoung Kwon Lee, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo Marques, Sanghoon Shin, Jung Hyun Choi, Kavitha Chinnaiyan, Martin Hadamitzky, Edoardo Conte, Daniele Andreini, Gianluca Pontone, Matthew J Budoff, Jonathon A Leipsic, Gilbert L Raff, Renu Virmani, Habib Samady, Peter H Stone, Daniel S Berman, Jagat Narula, Jeroen J Bax, Hyuk-Jae Chang, James K Min, and Leslee J Shaw
Subjects: Medicine, Science
Abstract: OBJECTIVES:To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND:Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS:Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS:The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS:An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level.
Published: 2020
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12. Towards UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): protocol for an evaluation of the requirements for arthroplasty follow-up, and the production of consensus-based recommendations

Author: Andrew Judge, Sarah R Kingsbury, Nigel K Arden, Jamie Matu, Jamie O’Shea, Rafael Pinedo-Villanueva, Lindsay K Smith, Christine M Thomas, Robert M West, and Martin H Stone
Subjects: Medicine
Abstract: IntroductionHip and knee arthroplasties have revolutionised the management of degenerative joint diseases and, due to an ageing population, are becoming increasingly common. Follow-up of joint prostheses is to identify problems in symptomatic or asymptomatic patients due to infection, osteolysis, bone loss or potential periprosthetic fracture, enabling timely intervention to prevent catastrophic failure at a later date. Early revision is usually more straight-forward surgically and less traumatic for the patient. However, routine long-term follow-up is costly and requires considerable clinical time. Therefore, some centres in the UK have curtailed this aspect of primary hip and knee arthroplasty services, doing so without an evidence base that such disinvestment is clinically or cost-effective.MethodsGiven the timeline from joint replacement to revision, conducting a randomised controlled trial (RCT) to determine potential consequences of disinvestment in hip and knee arthroplasty follow-up is not feasible. Furthermore, the low revision rates of modern prostheses, less than 10% at 10 years, would necessitate thousands of patients to adequately power such a study. The huge variation in follow-up practice across the UK also limits the generalisability of an RCT. This study will therefore use a mixed-methods approach to examine the requirements for arthroplasty follow-up and produce evidence-based and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Four interconnected work packages will be completed: (1) a systematic literature review; (2a) analysis of routinely collected National Health Service data from five national data sets to understand when and which patients present for revision surgery; (2b) prospective data regarding how patients currently present for revision surgery; (3) economic modelling to simulate long-term costs and quality-adjusted life years associated with different follow-up care models and (4) a Delphi-consensus process, involving all stakeholders, to develop a policy document which includes a stratification algorithm to determine appropriate follow-up care for an individual patient.Ethics and DisseminationFavourable ethical opinion has been obtained for WP2a (RO-HES) (220520) and WP2B (220316) from the National Research Ethics Committee. Following advice from the Confidentiality Advisory Group (17/CAG/0122), data controllers for the data sets used in WP2a (RO-HES) – NHS Digital and The Phoenix Partnership – confirmed that Section 251 support was not required as no identifiable data was flowing into or out of these parties. Application for approval of WP2a (RO-HES) from the Independent Group Advising on the Release of Data (IGARD) at NHS Digital is in progress (DARS-NIC-147997). Section 251 support (17/CAG/0030) and NHS Digital approval (DARS-NIC-172121-G0Z1H-v0.11) have been obtained for WP2a (NJR-HES-PROMS). ISAC (11_050MnA2R2) approval has been obtained for WP2a (CPRD-HES).
Published: 2019
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13. Individual components of the SWI/SNF chromatin remodelling complex have distinct roles in memory neurons of the Drosophila mushroom body

Author: Melissa C. Chubak, Kevin C. J. Nixon, Max H. Stone, Nicholas Raun, Shelby L. Rice, Mohammed Sarikahya, Spencer G. Jones, Taylor A. Lyons, Taryn E. Jakub, Roslyn L. M. Mainland, Maria J. Knip, Tara N. Edwards, and Jamie M. Kramer
Subjects: SWI/SNF complex, Drosophila melanogaster, Mushroom body, Memory, Neuron remodelling, Intellectual disability, Medicine, Pathology, RB1-214
Abstract: Technology has led to rapid progress in the identification of genes involved in neurodevelopmental disorders such as intellectual disability (ID), but our functional understanding of the causative genes is lagging. Here, we show that the SWI/SNF chromatin remodelling complex is one of the most over-represented cellular components disrupted in ID. We investigated the role of individual subunits of this large protein complex using targeted RNA interference in post-mitotic memory-forming neurons of the Drosophila mushroom body (MB). Knockdown flies were tested for defects in MB morphology, short-term memory and long-term memory. Using this approach, we identified distinct roles for individual subunits of the Drosophila SWI/SNF complex. Bap60, Snr1 and E(y)3 are required for pruning of the MBγ neurons during pupal morphogenesis, while Brm and Osa are required for survival of MBγ axons during ageing. We used the courtship conditioning assay to test the effect of MB-specific SWI/SNF knockdown on short- and long-term memory. Several subunits, including Brm, Bap60, Snr1 and E(y)3, were required in the MB for both short- and long-term memory. In contrast, Osa knockdown only reduced long-term memory. Our results suggest that individual components of the SWI/SNF complex have different roles in the regulation of structural plasticity, survival and functionality of post-mitotic MB neurons. This study highlights the many possible processes that might be disrupted in SWI/SNF-related ID disorders. Our broad phenotypic characterization provides a starting point for understanding SWI/SNF-mediated gene regulatory mechanisms that are important for development and function of post-mitotic neurons.
Published: 2019
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14. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah 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Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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15. Weightlifting for Children and Adolescents: A Narrative Review

Author: Michael H. Stone, Kyle C. Pierce, and W. Guy Hornsby
Subjects: Severe injury, Adolescent, Weight Lifting, biology, Athletes, business.industry, Resistance training, Resistance Training, Physical Therapy, Sports Therapy and Rehabilitation, Athletic Performance, biology.organism_classification, Developmental psychology, Growth development, Special Issue: Training the Adolescent Athlete, Humans, Medicine, Orthopedics and Sports Medicine, Narrative review, Muscle Strength, Child, Training program, Construct (philosophy), business, Exercise
Abstract: The involvement of youth in the sport of weightlifting and the use of weightlifting methods as part of training for youth sport performance appears to be increasing. Weightlifting for children and adolescents has been criticized in some circles and is a controversial aspect of resistance training for young people. Although injuries can occur during weightlifting and related activities, the incidence and rate of injury appear to be relatively low and severe injury is uncommon. A number of performance, physical, and physiological variables, such as body composition, strength, and power, are improved by weightlifting training in children, adolescents, and young athletes. Manipulating program variables, when appropriate, can have a substantial and profound influence on the psychological, physiological, physical, and performance aspects of weightlifters. An understanding of the sport, scientific training principles, and musculoskeletal growth development is necessary to properly construct a reasonable and appropriate training program. A scientific background aids in providing an evidenced basis and sound rationale in selecting appropriate methods and directing adaptations toward more specific goals and enables the coach to make choices about training and competition that might not otherwise be possible. If weightlifting training and competition are age group appropriate and are properly supervised, the sport can be substantially safe and efficacious.
Published: 2021
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16. <scp>Pharmacist‐prescribed</scp> hormonal contraception services: A systematic review of implementation studies

Author: Jenny L. Newlon, Jason B. Reed, Rebecca H. Stone, Kennedi G. Satterfield, and Ashley H. Meredith
Subjects: medicine.medical_specialty, business.industry, Hormonal contraception, Family medicine, Pharmacist, Pharmaceutical Science, Medicine, Pharmacology (medical), Pharmacy, business
Published: 2021
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17. Validation of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis as the Cause of <scp>End‐Stage</scp> Renal Disease in the <scp>US</scp> Renal Data System

Author: Xiaoqing Fu, Yuqing Zhang, Hyon K. Choi, John H. Stone, Zachary S. Wallace, and Claire Cook
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Brief Report, viruses, Diseases of the musculoskeletal system, Disease, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, End stage renal disease, RC925-935, Rheumatology, Internal medicine, Cohort, medicine, Brief Reports, Renal biopsy, Granulomatosis with polyangiitis, Vasculitis, business, Nephritis, Anti-neutrophil cytoplasmic antibody
Abstract: Objective The objective of this study was to validate the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). Methods We identified patients with ESRD in the Mass General Brigham (MGB) health care system who were enrolled in the USRDS. The health records of those with AAV listed as the primary cause of ESRD in the USRDS were reviewed to confirm the diagnosis and estimate positive predictive value (PPV). Sensitivity was estimated by evaluating the primary cause of ESRD listed in the USRDS for patients with ESRD due to AAV in the MGB AAV cohort. Results We identified 89 MGB patients with ESRD due to AAV in the USRDS. Of these, 85 cases were confirmed to be true cases of AAV (PPV = 94%). Among the patients classified as having AAV, 84 (99%) had an ANCA test, which was predominantly myeloperoxidase/P-ANCA (47 [55%]); 36 (42%) had a renal biopsy, and all biopsies were supportive of the diagnosis. The majority (81 [90%]) was identified as AAV by International Classification of Diseases Ninth Revision or International Classification of Diseases 10th Revision codes for granulomatosis with polyangiitis (446.4 or M313.1). Of the 77 MGB AAV cohort patients with ESRD who were linked to the USRDS, 41 (53%) had AAV listed as the cause of ESRD; in the remainder, ESRD was attributed to nonspecific nephritis. Conclusion The diagnosis of AAV as the cause of ESRD in the USRDS has a high PPV; sensitivity was moderate. These findings support the continued use of the USRDS to study ESRD due to AAV.
Published: 2021
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18. Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis

Author: Gabriele Capurso, Marco Lanzillotta, Paolo Giorgio Arcidiacono, Zachary S. Wallace, Lorenzo Dagna, John H. Stone, Massimo Falconi, Omer Karadag, Andreu Fernández-Codina, and Emanuel Della-Torre
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, law.invention, Randomized controlled trial, Recurrence, law, Internal medicine, medicine, Humans, Adverse effect, Glucocorticoids, Autoimmune pancreatitis, Hepatology, business.industry, Gastroenterology, Publication bias, medicine.disease, Immunoglobulin G, Meta-analysis, IgG4-related disease, Rituximab, Immunoglobulin G4-Related Disease, business, Cohort study, medicine.drug
Abstract: Background Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment. Methods The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates. Results Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5–93.9) with no heterogeneity (I2 = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5–40.3) with moderate heterogeneity (I2 = 51%). A higher rate of relapse (35.9%, 95%CI 17.3–60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8–53) with substantial heterogeneity (I2 = 73.6%). No publication bias was observed. Conclusion Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.
Published: 2021
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19. Hybrid and Total Endovascular Approaches to Tandem Carotid Artery Lesions Have Similar Short- and Long-Term Outcomes

Author: Mark F. Conrad, Jahan Mohebali, Adam Tanious, Charles DeCarlo, Laura T. Boitano, David H. Stone, and W. Darrin Clouse
Subjects: Carotid Artery Diseases, Male, medicine.medical_specialty, Time Factors, Carotid arteries, medicine.medical_treatment, Carotid endarterectomy, 030204 cardiovascular system & hematology, Risk Assessment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Long term outcomes, Humans, cardiovascular diseases, Stroke, Aged, Endarterectomy, Carotid, business.industry, Mortality rate, Endovascular Procedures, Mean age, General Medicine, Middle Aged, medicine.disease, Surgery, Stenosis, Treatment Outcome, Female, Stents, Carotid stenting, Cardiology and Cardiovascular Medicine, business
Abstract: Addition of ipsilateral proximal endovascular intervention (PEI, common carotid/innominate) increases the risk of perioperative stroke/death for both carotid endarterectomy (CEA) and carotid stenting (CAS). However, these approaches have not been directly compared and is the subject of this study.VQI (2005-2020) was queried for CEA and CAS with PEI, excluding emergent, bilateral, and repeat procedures, patients with prior ipsilateral CAS, ICA lesions with stenosis50%, and transcarotid ICA stents. Primary outcome were the composite of perioperative stroke/death and long-term stroke/reintervention/death. Operative approach was evaluated with logistic regression, adjusted propensity scores, symptomatic status, and stenosis70%. Long-term outcomes were compared with Kaplan-Meier Analysis.There were 1,433 patients (795 endovascular;638 hybrid); mean age 69.8±9.4 years. Patients undergoing hybrid procedures were more likely to be female (49.4% vs. 37.5%; P0.001), less likely to have diabetes (29.5% vs. 38.2%; P P0.001), less likely to have a prior ipsilateral CEA (3.8% vs. 32.2%; P0.001), less likely to be symptomatic (34.6% vs. 52.8%; P0.001), and less likely to have70% stenosis (77.3% vs. 95.6%%; P0.001). Perioperative stroke/death was 3.6% for hybrid and 3.9% for endovascular approaches (P = 0.77). In the multivariable model, hybrid operative approach (compared to the total endovascular approach) was not significantly associated with stroke/death (OR 1.29; 95%CI: 0.55-3.07; P = 0.56). For the 981 patients with long-term follow-up (556 endovascular; 425 hybrid), 1-year freedom from stroke/reintervention/death was 94.0% (95%CI: 90.9%-96.0%) for hybrid approach vs. 92.3% (95%CI: 89.5%-94.4%) for endovascular approach (P = 0.27).Although simultaneous repair of tandem carotid lesions portends worse outcomes when compared to CEA or CAS alone, there was no difference in short or long-term stroke and death rates with a hybrid or totally endovascular approach. Therefore, it is reasonable to use either approach in the select patients who require simultaneous repair of both lesions.
Published: 2021
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20. Stress testing before abdominal aortic aneurysm repair does not lead to a reduction in perioperative cardiac events

Author: Stanislav Henkin, Jocelyn M. Beach, Bjoern D. Suckow, Falen Demsas, Philip P. Goodney, David H. Stone, Jesse A. Columbo, and Zachary J. Wanken
Subjects: Male, Percentile, medicine.medical_specialty, Time Factors, Stress testing, Myocardial Infarction, Myocardial Ischemia, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Humans, Medicine, Registries, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Healthcare Disparities, Practice Patterns, Physicians', Stroke, Aged, Retrospective Studies, Aged, 80 and over, Heart Failure, business.industry, Endovascular Procedures, Perioperative, Middle Aged, medicine.disease, Abdominal aortic aneurysm, Treatment Outcome, Heart Disease Risk Factors, Heart failure, Exercise Test, Cardiology, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Vascular Surgical Procedures, Mace, Aortic Aneurysm, Abdominal
Abstract: Stress testing is often used before abdominal aortic aneurysm (AAA) repair. Whether stress testing leads to a reduction in cardiac events after AAA repair has remained unclear. Our objective was to study the national stress test usage rates and compare the perioperative outcomes between centers with high and low usage of stress testing.We used the Vascular Quality Initiative to study patients who had undergone elective endovascular AAA repair (EVAR) or open AAA repair (OAR). We measured the usage rates of stress testing across centers and compared the Vascular Study Group of New England cardiac risk index (VSG-CRI) among patients who had and had not undergone preoperative stress testing. We determined the rate of major adverse cardiac events (MACE), a composite of perioperative myocardial infarction, stroke, heart failure exacerbation, and death across the centers. We compared the MACE and 1-year mortality between the centers in the highest quintile of stress test usage and the lowest quintile.We studied 43,396 EVAR patients and 8935 OAR patients across 324 centers. The median proportion of stress test usage across centers before EVAR was 35.9% and varied from 10.2% (5th percentile) to 73.7% (95th percentile), with similar variability for OAR (median, 57.9%; 5th percentile, 13.0%; 95th percentile, 86.0%). The mean VSG-CRI for the EVAR group with preoperative stress testing was 5.6 ± 2.1 compared with 5.4 ± 2.1 (P .001) for the EVAR group without preoperative stress testing. The findings were similar for OAR, with a VSG-CRI of 5.1 ± 2.0 vs 4.8 ± 2.1 (P .001) for those with and without preoperative stress testing, respectively. The rate of MACE was 1.8% after EVAR and 11.6% after OAR. The 1-year mortality was 4.6% for EVAR and 6.6% for OAR. The centers in the highest quintile of stress testing had a higher adjusted likelihood of MACE after both EVAR (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.37-2.30) and OAR (OR, 1.99; 95% CI, 1.53-2.59) but similar 1-year mortality (EVAR: OR, 1.18; 95% CI, 1.02-1.37; OAR: OR, 0.87; 95% CI, 0.65-1.17) compared with the centers in the lowest quintile. The VSG-CRI was not different between the high stress test centers (EVAR, 5.5 ± 2.1; OAR: 5.0 ± 2.0), and low stress test centers (EVAR, 5.5 ± 2.1; P = .403; OAR, 4.9 ± 2.0; P = .563).Stress test usage before AAA repair varied widely across Vascular Quality Initiative centers despite similar patient risk profiles. No reduction was observed in MACE or 1-year mortality among centers with high stress test usage. The value of routine stress testing before AAA repair should be reconsidered, and stress testing should be used more selectively, given these findings and the associated costs of widespread testing.
Published: 2021
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21. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Author: Yih Chang Lin, Maria Ibarra, Robert P. Sundel, Amy S. Turner, Ann Warner, Carol A. Langford, Andy Abril, Gordon H. Guyatt, Doyt L. Conn, Amy M. Archer, John H. Stone, Nedaa Husainat, Kathy A. Full, Reem A. Mustafa, Kevin Byram, Jason M. Springer, Rennie L. Rhee, Anisha B. Dua, Mohamad A. Kalot, Peter A. Merkel, Marat Turgunbaev, Sangeeta Sule, Mehrdad Maz, Susan Kim, Sharon A. Chung, Mark Gorelik, Peter C. Grayson, Omar I. Vitobaldi, Philip Seo, Alexandra Villa-Forte, Lisa Imundo, and Karen E. James
Subjects: medicine.medical_specialty, Consensus, Clinical Decision-Making, Immunology, Population, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Severity of Illness Index, Antibodies, Antineutrophil Cytoplasmic, Decision Support Techniques, Rheumatology, Maintenance therapy, medicine, Humans, Immunology and Allergy, Intensive care medicine, education, Anti-neutrophil cytoplasmic antibody, education.field_of_study, Evidence-Based Medicine, business.industry, Guideline, medicine.disease, Treatment Outcome, Adjunctive treatment, Microscopic polyangiitis, business, Granulomatosis with polyangiitis, Mepolizumab, Biomarkers, Immunosuppressive Agents, medicine.drug
Abstract: Objective To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. Conclusion This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.
Published: 2021
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22. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis

Author: Yih Chang Lin, Kevin Byram, Peter C. Grayson, Kathy A. Full, Jason M. Springer, Sharon A. Chung, Robert P. Sundel, Marat Turgunbaev, Maria Ibarra, Sangeeta Sule, Rennie L. Rhee, Amy S. Turner, Mark Gorelik, Mohamad A. Kalot, Peter A. Merkel, Carol A. Langford, Nedaa Husainat, Mehrdad Maz, Ann Warner, Amy M. Archer, Andy Abril, Doyt L. Conn, Karen E. James, Reem A. Mustafa, Anisha B. Dua, Philip Seo, Alexandra Villa-Forte, Gordon H. Guyatt, John H. Stone, Susan Kim, Lisa Imundo, and Omar I. Vitobaldi
Subjects: medicine.medical_specialty, Consensus, Clinical Decision-Making, Giant Cell Arteritis, Immunology, Population, MEDLINE, Decision Support Techniques, Rheumatology, Internal medicine, Humans, Immunology and Allergy, Medicine, Disease management (health), skin and connective tissue diseases, Intensive care medicine, education, Grading (education), Glucocorticoids, education.field_of_study, Evidence-Based Medicine, business.industry, Disease Management, Guideline, medicine.disease, Takayasu Arteritis, United States, Giant cell arteritis, Treatment Outcome, Drug Therapy, Combination, business, Vasculitis, Immunosuppressive Agents
Abstract: Objective To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.
Published: 2021
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23. Training for Muscular Strength: Methods for Monitoring and Adjusting Training Intensity

Author: W. Guy Hornsby, Christopher R. Bellon, Sophia Nimphius, Timothy J. Suchomel, and Michael H. Stone
Subjects: medicine.medical_specialty, biology, Sports medicine, Athletes, Resistance training, Training (meteorology), Physical Therapy, Sports Therapy and Rehabilitation, 030229 sport sciences, biology.organism_classification, Physical strength, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, One-repetition maximum, Training intensity, medicine, Orthopedics and Sports Medicine, 030212 general & internal medicine, Psychology
Abstract: Linear loading, the two-for-two rule, percent of one repetition maximum (1RM), RM zones, rate of perceived exertion (RPE), repetitions in reserve, set-repetition best, autoregulatory progressive resistance exercise (APRE), and velocity-based training (VBT) are all methods of adjusting resistance training intensity. Each method has advantages and disadvantages that strength and conditioning practitioners should be aware of when measuring and monitoring strength characteristics. The linear loading and 2-for-2 methods may be beneficial for novice athletes; however, they may be limited in their capacity to provide athletes with variation and detrimental if used exclusively for long periods of time. The percent of 1RM and RM zone methods may provide athletes with more variation and greater potential for strength-power adaptations; however, they fail to account for daily changes in athlete's performance capabilities. An athlete's daily readiness can be addressed to various extents by both subjective (e.g., RPE, repetitions in reserve, set-repetition best, and APRE) and objective (e.g., VBT) load adjustment methods. Future resistance training monitoring may aim to include a combination of measures that quantify outcome (e.g., velocity, load, time, etc.) with process (e.g., variability, coordination, efficiency, etc.) relevant to the stage of learning or the task being performed. Load adjustment and monitoring methods should be used to supplement and guide the practitioner, quantify what the practitioner 'sees', and provide longitudinal data to assist in reviewing athlete development and providing baselines for the rate of expected development in resistance training when an athlete returns to sport from injury or large training load reductions.
Published: 2021
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24. Ustekinumab for the Treatment of Giant Cell Arteritis

Author: Sebastian Unizony, John H. Stone, Mark Matza, and Ana D. Fernandes
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.disease, Gastroenterology, Clinical trial, 03 medical and health sciences, Giant cell arteritis, 0302 clinical medicine, Rheumatology, Prednisone, Internal medicine, Erythrocyte sedimentation rate, Ustekinumab, medicine, Clinical endpoint, Adverse effect, business, Prospective cohort study, medicine.drug
Abstract: Objective To evaluate the efficacy and safety of ustekinumab (UST) in giant cell arteritis (GCA). Methods We conducted a prospective, open-label trial of UST in patients with active new-onset or relapsing GCA. Active disease was defined as the presence of GCA symptoms and elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level within 6 weeks of baseline. All patients received a 24-week prednisone taper and subcutaneous UST 90 mg at baseline and at weeks 4, 12, 20, 28, 36, and 44. The primary endpoint, prednisone-free remission, was defined as the absence of relapse through week 52 and normalization of the ESR and CRP level. Relapse was defined as the recurrence of GCA symptoms requiring treatment intensification. A sensitivity analysis excluding ESR/CRP level normalization from the prednisone-free remission definition was performed. Results The study enrolled 13 patients (target sample size 20). Enrollment was closed prematurely after 7 of the initial 10 patients relapsed. Five patients (39%) had new-onset disease. The initial prednisone doses were 20 mg (1 patient), 40 mg (9 patients), and 60 mg (3 patients). All patients entered disease remission within 4 weeks of baseline. Only 3 (23%) achieved the primary endpoint. Of the 10 patients (77%) who failed to achieve the primary endpoint, 7 relapsed after a mean period of 23 weeks. The remaining 3 patients met the alternative definition of prednisone-free remission that did not require ESR/CRP level normalization. One serious adverse event occurred. Conclusion UST combined with 24 weeks of prednisone was associated with a high rate of treatment failure in this prospective GCA trial.
Published: 2021
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25. Evaluation of GLP-1 Receptor Agonists in Combination With Multiple Daily Insulin Injections for Type 2 Diabetes

Author: Kimberly Sassenrath, Rebecca H. Stone, and Beth Bryles Phillips
Subjects: Glycated Hemoglobin, business.industry, Insulin, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Pharmacology, medicine.disease, Glucagon-Like Peptide-1 Receptor, Hypoglycemia, 03 medical and health sciences, High dose insulin, 0302 clinical medicine, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Pharmacology (medical), 030212 general & internal medicine, business, Receptor, Glucagon-like peptide 1 receptor
Abstract: Objective: To assess the available literature evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with multiple daily insulin injections (MDII). Data Sources: A literature search of MEDLINE and Embase was performed (2004 to May 2020) using the following search terms: glucagon-like 1 receptor agonist, liraglutide, albiglutide, dulaglutide, exenatide, semaglutide, diabetes mellitus, and prandial insulin or bolus insulin. Additional references were obtained from cross-referencing the bibliographies of selected articles. Study Selection and Data Extraction: All information obtained from the searches were reviewed. All relevant trials are included in this review. Data Synthesis: Eight studies met criteria for inclusion. The addition of a GLP-1 RA to multiple daily insulin injections was associated with a reduction in A1c in 7 out of 8 studies, and weight loss in 5 studies. In studies that allowed insulin adjustment after the addition of GLP-1 RA, the average total daily insulin dose was reduced in 3 studies. When evaluated, hypoglycemia frequency or other adverse events were not increased when GLP-1 RAs were added to MDII. Relevance to Patient Care and Clinical Practice: Guidelines do not offer recommendations regarding the use of GLP-1 RAs in combination with MDII regimens. This review evaluates current studies demonstrating efficacy and safety considerations of this combination. Conclusions: While some studies did demonstrate an improvement in A1c and reduction in insulin doses without increased hypoglycemia, larger randomized controlled trials are needed to adequately assess the benefit and safety of GLP-1 RAs in combination with MDII.
Published: 2021
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26. Tocilizumab vs placebo for the treatment of giant cell arteritis with polymyalgia rheumatica symptoms, cranial symptoms or both in a randomized trial

Author: John H. Stone, Yves Luder, Andrey Pavlov, Robert Spiera, Jian Han, Min Bao, and Sebastian Unizony
Subjects: musculoskeletal diseases, medicine.medical_specialty, Giant Cell Arteritis, education, Antibodies, Monoclonal, Humanized, Placebo, Gastroenterology, law.invention, Polymyalgia rheumatica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, Randomized controlled trial, Prednisone, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, skin and connective tissue diseases, 030203 arthritis & rheumatology, business.industry, medicine.disease, Clinical trial, Giant cell arteritis, Anesthesiology and Pain Medicine, chemistry, Polymyalgia Rheumatica, business, Vasculitis, medicine.drug
Abstract: The randomized, placebo (PBO)-controlled GiACTA trial demonstrated the efficacy and safety of tocilizumab (TCZ) in patients with giant cell arteritis (GCA). The present study evaluated the efficacy of TCZ in patients with GCA presenting with polymyalgia rheumatica (PMR) symptoms only, cranial symptoms only or both PMR and cranial symptoms in the GiACTA trial.In GiACTA, 250 patients with GCA received either TCZ weekly or every other week plus a 26-week prednisone taper or PBO plus a 26- or 52-week prednisone taper. This post hoc analysis assessed baseline characteristics, sustained remission rate, number of flares, annualized flare rate, time to flare, cumulative prednisone dose, methotrexate use and safety in patients with PMR symptoms only, cranial symptoms only or both at baseline.Overall, 52 patients had PMR symptoms only, 94 had cranial symptoms only and 104 had both symptoms at baseline. At Week 52, rates of sustained remission were significantly higher with TCZ vs PBO in all 3 groups (PMR only, 45.2% vs 19.0%, P = 0.0446; cranial only, 60.3% vs 19.4%, P = 0.0001; PMR and cranial, 55.0% vs 11.4%, P 0.0001). Smaller proportions of TCZ-treated patients experienced disease flare than PBO-treated patients across all groups (PMR only, 41.9% vs 57.1%; cranial only, 20.7% vs 47.2%; PMR and cranial, 31.7% vs 81.8%). Annualized flare rate and risk of flare were significantly lower with TCZ vs PBO for patients with cranial symptoms only and both symptoms; they were numerically lower, but did not reach statistical significance, in the smaller group of patients with PMR symptoms only.TCZ improved clinical outcomes in patients who presented with PMR symptoms only, cranial symptoms only or both at baseline, suggesting that TCZ is effective in patients with GCA regardless of the presenting clinical phenotype.
Published: 2021
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27. Medicare costs for endovascular abdominal aortic aneurysm treatment in the Vascular Quality Initiative

Author: Spencer W. Trooboff, Barbara Gladders, Gregory Tsougranis, Zachary J. Wanken, Jesse A. Columbo, David H. Stone, Richard J. Powell, and Philip P. Goodney
Subjects: Male, medicine.medical_specialty, Time Factors, Databases, Factual, Cost-Benefit Analysis, 030204 cardiovascular system & hematology, Medicare, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Aneurysm treatment, Humans, Medicine, Registries, 030212 general & internal medicine, Medicare reimbursement, Hospital Costs, health care economics and organizations, Aged, Quality Indicators, Health Care, Aged, 80 and over, business.industry, Financial impact, Endovascular Procedures, Mean age, medicine.disease, United States, Abdominal aortic aneurysm, Surgery, Outcome and Process Assessment, Health Care, Treatment Outcome, Cumulative cost, Insurance, Health, Reimbursement, Retreatment, Cohort, Female, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract: Background Reintervention after endovascular repair (EVR) of abdominal aortic aneurysms is common. However, the cumulative financial impact of reintervention after EVR on a national scale is poorly defined. Our objective was to describe the cost to Medicare for aneurysm treatment (EVR plus reinterventions) among a cohort of patients with known follow-up for 5 years after repair. Methods We identified patients who underwent EVR within the Vascular Quality Initiative who were linked to their respective Medicare claims file (n = 13,995). We excluded patients who underwent EVR after September 30, 2010, and those who had incomplete Medicare coverage (n = 12,788). The remaining cohort (n = 1207) had complete follow-up until death or 5 years (Medicare data available through September 30, 2015). We then obtained and compiled the corresponding Medicare reimbursement data for the index EVR hospitalization and all subsequent reinterventions. Results We studied 1207 Medicare patients who underwent EVR and had known follow-up for reinterventions for 5 years. The mean age was 76.2 years (±7.1 years), 21.6% of patients were female, and 91.1% of procedures were elective. The Kaplan-Meier reintervention rate at 5 years was 18%. Among patients who underwent reintervention, 154 (73.7%) had a single reintervention, 40 (19.1%) had two reinterventions, and 15 (7.2%) had three or more reinterventions. The median cost to Medicare for the index EVR hospitalization was $25,745 (interquartile range, $21,131-$28,774). The median cost for subsequent reinterventions was $22,165 (interquartile range, $17,152-$29,605). The cumulative cost to Medicare of aneurysm treatment (EVR plus reinterventions) increased in a stepwise fashion among patients who underwent multiple reinterventions, with each reintervention being similar in cost to the index EVR. Conclusions The overall cost incurred by Medicare to reimburse for each reintervention after EVR is roughly the same as for the initial procedure itself, meaning that Medicare cost projections would be greater than $100,000 for any individual who undergoes an EVR with three reinterventions. The long-term financial impact of EVR must be considered by surgeons, patients, and healthcare systems alike as these cumulative costs may hinder the fiscal viability of an EVR-first therapeutic approach and highlight the need for judicious patient selection paradigms.
Published: 2021
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28. The financial evolution of endovascular aneurysm repair delivery in contemporary practice

Author: Jonathan Aaron Barnes, Richard J. Powell, Robert M. Zwolak, Phillip Goodney, Bjoern D. Suckow, Jesse A. Columbo, Jeanwan Kang, and David H. Stone
Subjects: Male, Time Factors, Total cost, Cost-Benefit Analysis, medicine.medical_treatment, Cost accounting, 030204 cardiovascular system & hematology, Medicare, Endovascular aneurysm repair, Centers for Medicare and Medicaid Services, U.S, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Practice Management, Medical, Humans, Medicine, Revenue, 030212 general & internal medicine, Hospital Costs, health care economics and organizations, Aged, Retrospective Studies, Aged, 80 and over, Finance, business.industry, Endovascular Procedures, Length of Stay, United States, Aortic Aneurysm, Blood Vessel Prosthesis, Outcome and Process Assessment, Health Care, Treatment Outcome, Cost driver, Insurance, Health, Reimbursement, Cohort, Female, Stents, Surgery, Fiscal sustainability, Cardiology and Cardiovascular Medicine, business, Delivery of Health Care, Medicaid
Abstract: Objective The fiscal impact of endovascular repair (EVR) of aortic aneurysms and the requisite device costs have previously highlighted the tenuous long-term financial sustainability among Medicare beneficiaries. The Centers for Medicare & Medicaid Services have since reclassified EVR remuneration paradigms with new Medicare Severity Diagnosis-Related Groups (MS-DRGs) intended to better address the procedure's cost profile. The impact of this change remains unknown. The purpose of this analysis was to compare EVR-specific costs and revenue among Medicare beneficiaries both before and after this change. Methods All infrarenal EVRs performed in fiscal years (FYs) 2014 and 2015, before the MS-DRG change, and those performed in FYs 2017 and 2018, after the MS-DRG change, were identified using the DRG codes 238 (n = 108) and 269 (n = 84), respectively. We then identified those who were treated according to the instructions for use guidelines with a single manufacturer's device and billed to Medicare (n = 23 in FY14-15; n = 22 in FY17-18). From these cohorts, we determined total procedure technical costs, technical revenue, and net technical margin in conjunction with the hospital finance department. Results were then compared between these two groups. Results The two cohorts demonstrated similar demographic profiles (FY14-15 vs FY17-18 cohort: age, 78 years vs 74 years; median length of stay, 1.0 day vs 1.0 day). Mean total technical costs were slightly higher in the FY17-18 group ($24,511 in FY14-15 vs $26,445 in FY17-18). Graft implants continued to account for a significant portion of the total cost, with the device cost accounting for 56% of the total procedure costs in both cohorts. Net revenue was greater in the FY17-18 group by $5800 ($30,698 in FY14-15 vs $36,498 in FY17-18), resulting in an increased overall margin in the FY17-18 group compared with the FY14-15 group ($6188 in FY14-15 vs $10,053 in FY17-18). Conclusions Device costs remain the single greatest cost driver associated with EVR delivery. DRG reclassification of EVR to address total procedure and implant costs appears to better address the requisite associated procedure costs and may thereby better support long-term fiscal sustainability of this procedure for hospitals and health systems alike.
Published: 2021
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29. Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis

Author: Cory A. Perugino, Dinesh Khanna, Juhi Somani, Daniel C. Chung, Ramnik J. Xavier, Damian R. Plichta, Matthieu Pichaud, Shiv Pillai, Hera Vlamakis, Zachary S. Wallace, Ana D. Fernandes, Harri Lähdesmäki, and John H. Stone
Subjects: 0301 basic medicine, lcsh:QH426-470, Firmicutes, lcsh:Medicine, Autoimmunity, Disease, Biology, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, Fibrosis, Genetics, medicine, Humans, Microbiome, Alistipes, skin and connective tissue diseases, Molecular Biology, Genetics (clinical), 030203 arthritis & rheumatology, Gut microbiome, Scleroderma, Systemic, integumentary system, Bacteroidetes, Multiple sclerosis, Research, lcsh:R, medicine.disease, biology.organism_classification, Extracellular Matrix, Gastrointestinal Microbiome, lcsh:Genetics, 030104 developmental biology, Case-Control Studies, Immunology, IgG4-RD, Molecular Medicine, Systemic sclerosis, IgG4-related disease, Immunoglobulin G4-Related Disease, Bacteroides, Signal Transduction
Abstract: Background Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors. Methods The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases. Results Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism. Conclusions These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.
Published: 2021

30. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

Author: Sebastian Unizony, Zsofia D. Drobni, Cory A. Perugino, Deborah S. Collier, Janeth Yinh, Chana A. Sacks, Brian C. Healy, John H. Stone, Ana D. Fernandes, Michael Dougan, Allison K. Scherer, Kathryn Bowman, Harry M Schrager, Crystal M. North, Michael K. Mansour, Nina Lin, Eric A. Meyerowitz, Sarah Nikiforow, Amna Zafar, Rachel Wallwork, Mark Matza, Yuan Di C. Halvorsen, Jorge Fleisher, Jonathan Dau, Michael D. Pincus, Arthur Y. Kim, Matthew J. Frigault, Brittany Weber, David S. Huckins, Ana Maria Bensaci, Liam Harvey, Ruta Shah, Megan Lockwood, Tara K. Thurber, Pritha Sen, Manish Sagar, Andrea S. Foulkes, Tomas G. Neilan, Zeina Dagher, Nora Horick, Ann E. Woolley, Minna J. Kohler, Naomi Serling-Boyd, Sara R. Schoenfeld, Matthew Axelrod, Caroline Cubbison, Marcy B. Bolster, and Kristin M. D’Silva
Subjects: Mechanical ventilation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, General Medicine, 030204 cardiovascular system & hematology, Placebo, Confidence interval, law.invention, Discontinuation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, chemistry, Randomized controlled trial, law, Internal medicine, Medicine, Intubation, 030212 general & internal medicine, business
Abstract: BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).
Published: 2020
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31. The Vascular Implant Surveillance and Interventional Outcomes (VISION) Coordinated Registry Network: An effort to advance evidence evaluation for vascular devices

Author: Salvatore T. Scali, Sarah E. Deery, Jens Eldrup-Jorgensen, Leila Mureebe, Marc L. Schermerhorn, Mahmoud B. Malas, Scott Williams, Pablo Morales, Roberta A Bloss, Danica Marinac-Dabic, Adam W. Beck, Philip P. Goodney, Graham Roche-Nagle, Art Sedrakyan, Brian Pullin, Jessica P. Simons, Greg Tsougranis, Grace J. Wang, David H. Stone, Daniel J. Bertges, Matthew W. Mell, and Misti L. Malone
Subjects: medicine.medical_specialty, Time Factors, International Cooperation, media_common.quotation_subject, Population health, 030204 cardiovascular system & hematology, Public-Private Sector Partnerships, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Product Surveillance, Postmarketing, medicine, Humans, Quality (business), Regulatory science, Registries, 030212 general & internal medicine, media_common, Evidence-Based Medicine, Data collection, United States Food and Drug Administration, business.industry, Endovascular Procedures, Equipment Design, Vascular surgery, medicine.disease, United States, Intervention (law), Treatment Outcome, Equipment and Supplies, Population Surveillance, General partnership, Surgery, Patient Safety, Medical emergency, Cardiology and Cardiovascular Medicine, Vascular implant, business, Vascular Surgical Procedures
Abstract: The Vascular Implant Surveillance and Interventional Outcomes Network (VISION) is a Coordinated Registry Network (CRN) a member of Medical Device Epidemiology Network, a U.S. Food and Drug Administration (FDA)-supported global public-private partnership that seeks to advance the collection and use of real-world data to improve patient outcomes. The VISION CRN began in September 2015 and held its first strategic meeting on September 10, 2018, at the FDA headquarters in Silver Spring, Maryland. VISION is a collaboration of the Vascular Quality Initiative (VQI), the FDA, and other stakeholders. At this annual meeting, leaders from the FDA, VQI, industry representatives, population health researchers, and regulatory science experts gathered to discuss strategic goals and opportunities for VISION. One of the key focus areas for VISION is linkage of VQI registry data to Medicare, longitudinal data sources maintained by various states, and other relevant data sources, as a model for efficient, cost-saving, and effectual evidence generation and appraisal. This would provide the means to expand data collection, assess long-term procedural outcomes across the carotid, lower extremity, aortic, and venous intervention datasets, and execute registry-based trials through the CRN structure in an efficient, cost-effective manner. Looking forward, VISION strives to validate long-term outcome data in the VQI using industry datasets, in hopes of using CRNs to make device regulatory decisions. With the guidance of a steering committee, VISION will provide vascular surgeons, industry, and regulators the appropriate data to improve care for patients with vascular disease.
Published: 2020
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32. Prostate and pancreas involvement are linked in IgG4-related disease

Author: Chin-Lee Wu, Aileen O'Shea, Musie Ghebremichael, John H. Stone, Liam Harvey, Cory A. Perugino, Rory Crotty, Vikram Deshpande, Zachary S. Wallace, Hang Liu, Mukesh G. Harisinghani, and Ajay Nehra
Subjects: Male, medicine.medical_specialty, Urinary system, medicine.medical_treatment, Prostatitis, Disease, Gastroenterology, Autoimmune Diseases, Targeted therapy, Rheumatology, Prostate, Internal medicine, parasitic diseases, medicine, Humans, skin and connective tissue diseases, Glucocorticoids, Pancreas, Autoimmune pancreatitis, business.industry, medicine.disease, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Immunoglobulin G, IgG4-related disease, Immunoglobulin G4-Related Disease, business
Abstract: Prostate involvement by IgG4-related disease (IgG4-RD) is a rarely described organ manifestation and knowledge regarding its frequency and clinical features is limited.From a single-center cohort, 168 male patients were examined who satisfied the 2019 ACR/EULAR classification criteria or 2012 consensus histopathologic criteria for IgG4-RD.Prostate involvement were identified in 25 (15%) of these cases. The majority of patients with IgG4-RD involving the prostate gland (80%) were symptomatic at presentation with incomplete voiding (64%), urinary frequency (52%), and urinary hesitancy (48%) being the most common complaints. The radiologic presentation of prostate disease is most often a focal abnormality suggesting inflammation rather than a mass lesion. While most patients with IgG4-related prostate disease (89%) experienced recurrence after or during glucocorticoid tapering, patients treated with B cell targeted therapy in this series experienced clinical improvement and were tapered off of glucocorticoids. Additionally, patients with IgG4-RD involving the pancreas (p = 0.001) were more likely to have prostate involvement than were those with other types of organ involvement.This report provides the first comprehensive clinical description of IgG4-RD involving the prostate gland and links this manifestation with pancreatic involvement.
Published: 2020
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33. Adverse cardiac events after vascular surgery are prevalent despite negative results of preoperative stress testing

Author: Bjoern D. Suckow, Philip P. Goodney, Daniel B. Walsh, J Aaron Barnes, Richard J. Powell, David H. Stone, Jesse A. Columbo, and Douglas W. Jones
Subjects: Male, medicine.medical_specialty, Heart Diseases, medicine.medical_treatment, Clinical Decision-Making, Stress testing, 030204 cardiovascular system & hematology, Risk Assessment, Endovascular aneurysm repair, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Preoperative Care, Odds Ratio, medicine, Humans, Hospital Mortality, Vascular Diseases, 030212 general & internal medicine, Elective surgery, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Incidence, Patient Selection, Cardiac stress test, Odds ratio, Middle Aged, Vascular surgery, medicine.disease, Abdominal aortic aneurysm, Surgery, Treatment Outcome, Elective Surgical Procedures, Heart Disease Risk Factors, Heart failure, Exercise Test, Female, Cardiology and Cardiovascular Medicine, business, Negative Results, Vascular Surgical Procedures
Abstract: Objective Cardiac risk assessment is a critical component of vascular disease management before surgical intervention. The predictive risk reduction of a negative cardiac stress test result remains poorly defined. The objective of this study was to compare the incidence of postoperative cardiac events among patients with negative stress test results vs those who did not undergo testing. Methods We reviewed all patients who underwent elective open abdominal aortic aneurysm repair, suprainguinal bypass, endovascular aneurysm repair (EVAR), carotid endarterectomy (CEA), and infrainguinal bypass within the Vascular Study Group of New England from 2003 to 2017. We excluded patients with positive stress test results (n = 3312) and studied two mutually exclusive groups: elective surgery patients with a negative stress test result and elective surgery patients with no stress test (total n = 26,910). The primary outcome was a composite of in-hospital postoperative cardiac events (dysrhythmia, heart attack, heart failure) or death. Results A preoperative stress test was obtained in 66.3% of open repairs, 42.8% of suprainguinal bypasses, 37.1% of EVARs, 36.0% of CEAs, and 31.2% of infrainguinal bypasses. The proportion of patients receiving a preoperative stress test varied widely across centers, from 37.1% to 80.0%. The crude odds ratio of in-hospital postoperative cardiac event or death was 1.37 (95% confidence interval [CI], 1.07-1.76) for open repair and 1.52 (CI, 1.13-2.03) for suprainguinal bypass, indicating that patients with negative stress test results before these procedures were 37% and 52% more likely to suffer a postoperative event or die compared with patients selected to proceed directly to surgery without testing. Conversely, the crude odds ratio was 0.92 (CI, 0.66-1.29) for EVAR, 0.92 (CI, 0.70-1.21) for CEA, and 1.13 (CI, 0.90-1.40) for infrainguinal bypass, indicating that patients undergoing these procedures had a similar likelihood of sustaining an event whether they had a negative stress test result or proceeded directly to surgery without a stress test. Conclusions The use of cardiac stress testing before vascular surgery varies widely throughout New England. Whereas patients are often appropriately selected to proceed directly to surgery, a negative preoperative stress test result should not assuage the concern for an adverse outcome as these patients retain a substantial likelihood of cardiac events, especially after large-magnitude procedures.
Published: 2020
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34. Outcomes of Innominate Artery Revascularization Through Endovascular, Hybrid, or Open Approach

Author: Joseph P. DeSimone, Zachary J. Wanken, Bjoern D. Suckow, Philip P. Goodney, Richard J. Powell, Jesse A. Columbo, David H. Stone, and Nikolaos Zacharias
Subjects: Male, medicine.medical_specialty, Time Factors, Databases, Factual, medicine.medical_treatment, Carotid endarterectomy, 030204 cardiovascular system & hematology, Revascularization, Embolic Protection Devices, 030218 nuclear medicine & medical imaging, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Right Common Carotid Artery, Risk Factors, Angioplasty, medicine, Humans, Carotid Stenosis, Vascular Calcification, Brachiocephalic Trunk, Aged, Endarterectomy, Aged, 80 and over, Endarterectomy, Carotid, business.industry, General Medicine, Perioperative, Middle Aged, Atherosclerosis, medicine.disease, Blood Vessel Prosthesis, Surgery, Stenosis, Treatment Outcome, Median sternotomy, Retreatment, Female, Stents, Cardiology and Cardiovascular Medicine, business, Angioplasty, Balloon
Abstract: Background Atherosclerotic disease of the innominate artery (IA) is rare and can lead to cerebral, upper extremity, and vertebral steal symptoms. Nonocclusive lesions can be treated with endovascular interventions, often with a hybrid approach while performing a right carotid endarterectomy (RCEA). Calcified IA lesions have a high risk of embolization to bilateral cerebral hemispheres. Occlusive lesions may require treatment through a median sternotomy and bypass. The purpose of our study is to review our short-term and long-term outcomes of IA revascularization. Methods Our operative database was used to identify patients who underwent IA revascularization between January 1998 and December 2018. Patients who underwent innominate artery stenting (IAS), combined with RCEA and IAS as well as aortoinnominate bypass (AIB), were identified. Our primary end points were freedom from neurologic event, all-cause mortality, and need for reintervention. Results Thirty-three patients (18 females [55%]) who underwent IA revascularization were identified. Average age was 67 ± 8 years, and mean clinical follow-up was 51 ± 21 months. Most patients (30 [91%]) were on a statin and antiplatelet therapy. Twenty-one patients (64%) were symptomatic. Twelve patients (36%) were asymptomatic and underwent combined RCEA with retrograde IAS for critical right carotid stenosis and IA stenosis. Preoperative imaging included a carotid duplex and computed tomography angiography. Eighteen patients (55%) underwent RCEA + IAS, 11 patients (33%) underwent isolated IAS, and 4 patients (12%) underwent AIB. In our attempt to protect bilateral hemispheres during IAS for heavily calcified lesions, we used right common carotid artery (CCA) clamping although open exposure and left CCA embolic protection filter was placed through transfemoral approach. Patients who underwent AIB had chronic heavily calcified IA occlusions or occluded IA stents with failed endovascular interventions. Perioperative stroke rate was 3%, involving 1 patient who developed reperfusion syndrome after RCEA + IAS. Perioperative mortality was 0%. Long-term stroke rate was 0%, and long-term mortality was 15% (5 of 33) because of cardiac disease. Overall restenosis rate was 9%, involving 3 patients who required secondary interventions for IA in-stent restenosis. Conclusions IA interventions through a hybrid approach or an open approach are safe, with acceptable perioperative stroke and mortality rates. Long-term patency of these interventions is acceptable. Bilateral cerebral embolic protection can be accomplished by clamping the right CCA through an open exposure and placing a filter in the left CCA through a transfemoral approach. Patients undergoing IAS appear to have a higher rate of restenosis compared with AIB, and therefore, close follow-up with noninvasive imaging is recommended.
Published: 2020
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35. IgG4-related disease: an update on pathophysiology and implications for clinical care

Author: John H. Stone and Cory A. Perugino
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, business.industry, Disease, Bioinformatics, medicine.disease, Pathophysiology, Pathogenesis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Immune system, Rheumatology, Immunoglobulin class switching, parasitic diseases, medicine, Cytotoxic T cell, IgG4-related disease, business, B cell
Abstract: IgG4-related disease (IgG4-RD) has only existed as a unique disease entity since 2003, yet remarkable progress has already been achieved in describing the essential features of the disease. A framework for systematic clinical studies has been created by the development of a quantitative disease activity tool (the IgG4-RD Responder Index) and the validation of classification criteria, both of which were the products of international, multi-centre investigations. In addition, substantial strides have been made in understanding the pathophysiology of IgG4-RD. In particular, the central role of B cells in the disease has been demonstrated by both the robust clinical responsiveness of IgG4-RD to B cell depletion and by the identification of multiple self-antigens that promote B cell expansion. CD4+ T cells have also been investigated in detail; CD4+ cytotoxic T lymphocytes (suspected of promoting disease) and a specific T follicular helper cell subset that contributes to IgG4 isotype switching have both been defined by multiple groups. The mechanisms by which these immune cells converge on target tissues, interact with fibroblasts and promote tissue remodelling are beginning to be understood and will be an important research focus in the coming years. Over the past few years, considerable advances have been made in understanding the pathogenesis of IgG4-related disease. Our increased knowledge of the important roles of B cells and T cells is now starting to make its way into the clinic.
Published: 2020
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36. On 'The Basics of Training for Muscle Size and Strength'

Author: Michael W. Ramsey, Brad H. DeWeese, Hugh Lamont, Andrew C. Fry, Kyle C. Pierce, Keijo Häkkinen, Caleb D. Bazyler, J. M. McBride, Guy Hornsby, Robert D. Chetlin, Daniel Gahreman, Chad Kersick, Timothy J. Suchomel, Jakob L. Vingren, Jacob E. Earp, Christopher B. Taber, Michael H. Stone, Kyle Travis, Robert U. Newton, Bret Comstock, Hugo A. P. Santana, Andrew J. Galpin, Dylan G. Suarez, Steven J. Fleck, Kevin M. Carroll, Paul Comfort, Dan Wathen, Cody T. Haun, Kent J. Adams, George K. Beckham, William J. Kraemer, Disa L. Hatfield, Sandor Dorgo, Margaret E. Stone, Satoshi Mizuguchi, Aaron J. Cunanan, Clive Brewer, John Garhammer, John P. Wagle, Stuart N. Guppy, N. Travis Triplett, G. Gregory Haff, and Nicholas A. Ratamess
Subjects: medicine.medical_specialty, Text mining, Muscle size, Physical medicine and rehabilitation, business.industry, Sports science, MEDLINE, medicine, Training (meteorology), Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, business, Psychology
Published: 2020
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37. Evaluation of force-time curve analysis methods in the isometric mid-thigh pull test

Author: Michael H. Stone, Xingda Qu, and Junshi Liu
Subjects: 0206 medical engineering, Curve analysis, Physical Therapy, Sports Therapy and Rehabilitation, 030229 sport sciences, 02 engineering and technology, Isometric exercise, Thigh, 020601 biomedical engineering, Test (assessment), 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, medicine, Orthopedics and Sports Medicine, Analysis method, Force time curve, Mathematics, Biomedical engineering
Abstract: The purpose of this study was to evaluate the manual and automatic analysis methods for force-time curve analysis of the isometric mid-thigh pull (IMTP) test. The visual analysis, first derivative analysis and threshold analysis methods were used to analyse onset time and time-specific forces at 50 ms, 90 ms, 200 ms and 250 ms on the force-time curve. Ninety-three collegiate sports athletes' trials were selected and analysed by each method. The visual analysis method was set as the reference method for paired comparisons with the first derivative analysis method and threshold analysis method. Onset time comparisons revealed that the first derivative analysis method was comparable with the visual analysis method with average difference at about 30 ms. Results from the weighted least products regression analysis and the Bland-Altman analysis showed that large fixed bias confounded by proportional bias existed in the threshold analysis method, and time-specific force variables obtained from the first derivative analysis method were closer to those from the visual analysis method when compared with the threshold analysis method. These findings suggest that the first derivative analysis method could be an effective tool for force-time curve analysis of the IMTP test.
Published: 2020
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38. Outpatient, Home-Based Physical Therapy Promotes Decreased Length of Stay and Post-Acute Resource Utilization After Total Joint Arthroplasty

Author: Andrea H. Stone, Amanda L. Adkins, Justin Turcotte, Nandakumar Menon, Paul J. King, and James H. MacDonald
Subjects: Male, medicine.medical_specialty, Joint arthroplasty, Arthroplasty, Replacement, Hip, Total knee arthroplasty, 03 medical and health sciences, 0302 clinical medicine, Outpatients, Humans, Medicine, Orthopedics and Sports Medicine, Prospective Studies, Prospective cohort study, Physical Therapy Modalities, Aged, Retrospective Studies, 030222 orthopedics, Episode of care, business.industry, Length of Stay, Home based, Patient Discharge, Physical therapy, Female, Skilled Nursing Facility, business, Body mass index, Resource utilization
Abstract: Background Patients and healthcare systems are increasingly focused on evaluating interventions that increase the value of care delivered. Our objective of this study is to evaluate early post-operative outcomes among those patients who underwent total joint arthroplasty with and without the participation in our piloted Outpatient Physical Therapy Home Visits (OPTHV) program. Methods A retrospective analysis of patients undergoing total hip arthroplasty and total knee arthroplasty at a single institution from July 2016 to September 2017 was performed. Matched cohorts were compared according to OPTHV enrollment status. Results In total, 1729 patients were included in this study. Two hundred ninety-three patients were enrolled in OPTHV, while 1436 patients received institutional standard care. Patients were matched by gender (56.7% vs 57.7% female, P = .751), age (67.75 vs 66.95 years, P = .167), body mass index (30.18 vs 30.12 kg/m2, P = .859), and average American Society of Anesthesiologists score (2.31 vs 2.36, P = .131). OPTHV patients had a shorter length of stay (1.39 vs 1.64 days, P Conclusion OPTHV is a novel program that facilitates discharge home and decreased length of stay after total joint arthroplasty without increasing re-admissions or emergency room visits. Utilization of OPTHV may contribute toward reducing the episode of care costs by reducing utilization of skilled nursing facility and home health services. Further prospective studies are needed to evaluate the effect of OPTHV on the total cost of care and functional outcomes.
Published: 2020
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39. Infertility Management and Pharmacotherapy: What Every Pharmacist Should Know

Author: Nicole M. Lodise, Nicole E. Cieri-Hutcherson, John Brock Harris, Veronica Vernon, Rebecca H. Stone, Lamis R. Karaoui, and Lauren Lakdawala
Subjects: Counseling, Infertility, medicine.medical_specialty, Pharmacological management, Pharmacist, Pharmacists, 03 medical and health sciences, Professional Role, 0302 clinical medicine, Pharmacotherapy, Health care, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Medical prescription, Intensive care medicine, Patient Care Team, 030219 obstetrics & reproductive medicine, business.industry, Public health, Risk factor (computing), medicine.disease, United States, business
Abstract: Infertility is a significant public health concern in the United States. As such, utilization of infertility services, including pharmacotherapeutic treatments, is prevalent, and the role of the pharmacist as part of the health care team is essential. Pharmacists can assist patients by providing education on infertility causes, risk factor mitigation, referrals, nonpharmacologic and pharmacologic management options, navigation of the prescription process, and resource availability for the significant financial burden accompanying infertility treatment. In-depth pharmacotherapeutic information may not be readily available to pharmacists dispensing and counseling on these medications, and infertility management regimens are often varied and complicated requiring more in-depth counseling on use and administration. Given the complexity of infertility management, pharmacists are a valuable patient support and education resource. This article provides an in-depth review of infertility management strategies, both nonpharmacologic and pharmacologic.
Published: 2020
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40. A dynamic knee extension device improves flexion contracture before total knee arthroplasty: a randomized controlled trial

Author: M. Brook Fowler, Marc F. Brassard, Justin Turcotte, James H. MacDonald, Paul J. King, and Andrea H. Stone
Subjects: Flexion contracture, medicine.medical_specialty, Randomized controlled trial, business.industry, law, Total knee arthroplasty, Physical therapy, Medicine, Orthopedics and Sports Medicine, Knee extension, business, law.invention
Published: 2020
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41. Recent advances in the diagnosis and management of giant cell arteritis

Author: John H. Stone and Naomi Serling-Boyd
Subjects: 0301 basic medicine, medicine.medical_specialty, Biopsy, Giant Cell Arteritis, Disease, Antibodies, Monoclonal, Humanized, Sensitivity and Specificity, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, Prednisone, Positron Emission Tomography Computed Tomography, medicine, Humans, Adverse effect, Glucocorticoids, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, Ultrasound, medicine.disease, Temporal Arteries, Giant cell arteritis, 030104 developmental biology, chemistry, Positron emission tomography, Radiology, business, Glucocorticoid, medicine.drug
Abstract: Purpose of review Giant cell arteritis (GCA) has classically been diagnosed by temporal artery biopsy and treated with high-dose, long-term glucocorticoid therapy. Noninvasive imaging increasingly is employed for diagnostic purposes, but further studies are needed to determine the role of imaging in monitoring longitudinal disease activity. Glucocorticoid-sparing therapy mitigates the numerous adverse effects of glucocorticoids. This review addresses new developments in these areas. Recent findings For diagnosis, when performed at a center with expertise in its use, temporal artery ultrasound has an estimated sensitivity and specificity of 78 and 79%, respectively. State-of-the-art time-of-flight positron emission tomography/computed tomography (PET/CT) has an estimated sensitivity and specificity of 71 and 91%, respectively. The sensitivities of both imaging modalities decrease following glucocorticoid administration. Tocilizumab is an effective glucocorticoid-sparing therapy, demonstrating sustained glucocorticoid-free remission in 56% of patients receiving weekly tocilizumab compared with 18% of patients receiving a 52-week prednisone taper. The traditional acute phase reactants are of no value in patients treated with interleukin-6 receptor (IL6-R) blockade, and thus, the development of new biomarkers is an important priority in the field. Summary Noninvasive imaging techniques are increasingly used in the absence of temporal artery biopsy to confirm diagnostic suspicions of GCA. Tocilizumab reduces the cumulative glucocorticoid exposure and increases the rate of sustained remission. Ongoing efforts are directed towards new methods to identify disease flares.
Published: 2020
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42. The Acute Effects of Whole Body Vibration on Isometric Mid-Thigh Pull Performance

Author: Michael H. Stone, Mark A. South, W. Guy Hornsby, Hugh S. Lamont, G. Gregory Haff, and Jason D. Stone
Subjects: Acute effects, Orthodontics, business.industry, peak force, Repeated measures design, 030229 sport sciences, Isometric exercise, Thigh, force–time curve, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Rate of force development, medicine, Whole body vibration, 030212 general & internal medicine, Analysis of variance, strength, business, rate of force development
Abstract: The purpose of the present investigation was to examine the acute effects of whole body vibration (WBV) on isometric mid-thigh pull force&ndash, time curve (FTC) characteristics. Eleven recreationally trained subjects were randomly assigned to three treatment conditions: sham no vibration protocol (T1), vibration protocol 30 Hz 2&ndash, 4 mm amplitude (T2), and vibration protocol 30 Hz 2&ndash, 4 mm (T3). After completing a standardized warm-up, the subject stood on a vibration platform with the knee at a 120&deg, angle and performed one of the three interventions. Each treatment condition required the subject to stand on the platform for thirty-second treatments, each separated by thirty seconds of recovery. Five minutes after the completion of the treatment conditions, the subjects performed the isometric mid-thigh pull. All FTCs were analyzed with standardized procedures for peak force (PF) and peak rate of force development (PRFD). A 1 &times, 3 repeated measures analysis of variance (ANOVA) was used to compare the three treatments. Additionally, coefficients of variance (CV), as well as intraclass and interclass correlations, were performed. There were no significant differences (p &gt, 0.05) for any of the FTC analyses performed in this investigation. The CV and the 95% confidence interval (CI) indicate that the WBV protocol resulted in trivial changes in PF and beneficial changes in PRFD. A 30 Hz 2&ndash, 4 mm amplitude WBV does not result in a significant increase in isometric mid-thigh pull performance.
Published: 2020
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43. The Effect of Neuraxial Anesthesia on Postoperative Outcomes in Total Joint Arthroplasty With Rapid Recovery Protocols

Author: Andrea H. Stone, Josephine W. Formica, Ruby J. Gilmor, Justin Turcotte, and Paul J. King
Subjects: 030222 orthopedics, Joint arthroplasty, business.industry, Arthroplasty, Replacement, Hip, Discharge disposition, Retrospective cohort study, Length of Stay, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Anesthesia, Retrospective analysis, Humans, Medicine, Orthopedics and Sports Medicine, Hematocrit levels, Level iii, Arthroplasty, Replacement, Knee, business, Body mass index, Retrospective Studies, Total hip arthroplasty
Abstract: Compared to general anesthesia (GA), neuraxial anesthesia (NA) has been associated with improved outcomes after total joint arthroplasty (TJA). We examined the impact of NA on patient outcomes in an institution with an established rapid recovery protocol.This is a single-institution retrospective analysis of 5914 consecutive primary TJA performed from July 2015 to June 2018. Univariate tests and multivariate regression compared length of stay (LOS), transfusion rates, hematocrit levels, discharge disposition, and emergency room returns between patients receiving GA and NA.Patients receiving NA had a significantly shorter LOS (total hip arthroplasty [THA]: GA 1.74 vs NA 1.36 days, P.001; total knee arthroplasty [TKA]: GA 1.77 vs NA 1.64 days, P.001). Both THA and TKA patients receiving NA were less likely to require transfusion (THA: GA 5.8% vs NA 1.6%, P.001; TKA: GA 2.5% vs NA 0.5%, P.001) and had a higher postoperative hematocrit (THA: GA 32.50% vs NA 33.22%, P .001; TKA GA 33.57 vs NA 34.50%, P.001). Patients receiving NA were more likely to discharge home (THA: GA 83.4% vs NA 92.3%, P.001; TKA: GA 83.3% vs NA 86.3%, P = .010) (THA: NA adjusted OR [aOR] 2.04, P.001; TKA: NA aOR 1.23, P = .048) and had significantly lower rates of 90-day emergency room visits (THA: NA aOR 0.61, P = .005; TKA: NA aOR 0.74, P = .034).NA appears to contribute to decreased LOS, short-term complications, and transfusions while facilitating home discharge following TKA and THA. These trends are consistent when controlling for patient-specific risk factors, suggesting NA may enhance outcomes for patients with increased age, body mass index, and comorbidities.Level III Retrospective Cohort Study.
Published: 2020
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44. Temporomandibular joint osteoarthritis at Chelechol ra Orrak, Palau

Author: Greg C. Nelson, Scott M. Fitzpatrick, and Jessica H. Stone
Subjects: Adult, Male, Archeology, Palau, Context (language use), Osteoarthritis, Pathology and Forensic Medicine, stomatognathic system, Tooth loss, Humans, Medicine, 0601 history and archaeology, Areca, History, Ancient, Orthodontics, 060101 anthropology, 060102 archaeology, Dentition, business.industry, Dental occlusion, 06 humanities and the arts, Temporomandibular Joint Disorders, medicine.disease, Temporomandibular joint, stomatognathic diseases, medicine.anatomical_structure, Tooth wear, Mastication, Female, medicine.symptom, Malocclusion, business
Abstract: Objective To explore the frequency and severity of temporomandibular joint osteoarthritis (TMJ-OA) and its causative factors in a skeletal assemblage from the prehistoric site of Chelechol ra Orrak, Palau, western Micronesia. Materials 50 temporomandibular joint surfaces (mandibular condyles and articular eminences), representing a minimum of 22 adult individuals, 17 of which retain teeth. Methods Joint surfaces were macroscopically evaluated for characteristics associated with TMJ-OA and joint morphology. Dental remains were scored for tooth wear and staining. Results Nine individuals (40.1 %) displayed lesions typical of TMJ-OA. The strongest associations were between tooth wear and TMJ-OA. Conclusions Indirect effects of parafunctional dental activity appear to be a factor in TMJ-OA frequency at Chelechol ra Orrak. While betel nut chewing may be one of those activities, it does not appear to be solely driving the presence of TMJ-OA. Significance This study highlights the association between a specific parafunctional use of the temporomandibular joint and the potential pathological consequences. It also reinforces the need to carefully evaluate the archaeological context of skeletal remains in order to evaluate specific etiological factors in the presence of TMJ-OA in present and past populations. Limitations Sample sizes are limited in this study. This will increase as excavations continue. Suggestions for Further Research Because dental occlusion appears to be associated with TMJ-OA, focus on dental conditions affecting occlusal patterns, such as third molar agenesis, antemortem tooth loss, and malocclusion, and their relationship to TMJ-OA frequency, are recommended.
Published: 2020
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45. Lifetime Allergy Symptoms in IgG4-Related Disease: A Case-Control Study

Author: Cory A. Perugino, Aidan A. Long, John H. Stone, Liam Harvey, Tyler Harkness, Yuqing Zhang, Zachary S. Wallace, Hyon K. Choi, Emanuel Della-Torre, Rachel Wallwork, Samantha Sanders, and Xiaoqing Fu
Subjects: medicine.medical_specialty, Allergy, Disease, Article, Autoimmune Diseases, Rheumatology, Food allergy, Internal medicine, parasitic diseases, medicine, Hypersensitivity, Eosinophilia, Humans, skin and connective tissue diseases, integumentary system, business.industry, fungi, Case-control study, Odds ratio, medicine.disease, Confidence interval, Case-Control Studies, Immunoglobulin G, Etiology, Immunoglobulin G4-Related Disease, medicine.symptom, business
Abstract: The etiology of IgG4-related disease (IgG4-RD) is unknown, and there has been controversy over the significance of allergic conditions in IgG4-RD. We examined the prevalence of lifetime allergy symptoms in IgG4-RD and the association between these and IgG4-RD.We identified IgG4-RD patients and non-IgG4-RD controls without autoimmune conditions seen at a single center. IgG4-RD patients were classified using the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria. Allergy symptoms were ascertained by questionnaire. We assessed the association of IgG4-RD features with allergy symptoms. We compared the proportion of cases and controls with allergy symptoms using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) after matching cases and controls 1:1 by age and sex.Lifetime allergy symptoms were reported by 165 (71%) of 231 IgG4-RD patients. Aeroallergen symptoms were most commonly reported (n = 135, 58%), followed by skin allergy symptoms (n = 97, 42%) and food allergy symptoms (n = 47, 20%). IgG4-RD cases with a history of allergy symptoms were more likely to have head and neck involvement (OR 2.0 [95% CI 1.1-3.6]) and peripheral eosinophilia (OR 3.3 [95% CI 1.2-9.0]) than those without allergy symptoms. The prevalence of any allergy symptoms was similar between cases and controls (OR 0.7 [95% CI 0.4-1.1]); this remained consistent after stratifying by head and neck involvement.Lifetime allergy symptoms are common in IgG4-RD but are not reported more often in IgG4-RD compared to non-IgG4-RD patients without autoimmune conditions. These findings suggest that allergies are not uniquely associated with the pathogenesis or presentation of IgG4-RD.
Published: 2022

46. Curricular Considerations for Preparing Student Pharmacists to Prescribe Hormonal Contraception

Author: Jaini Patel, Regina Arellano, Sally Rafie, John Brock Harris, Kathleen Vest, Brooke Griffin, Nicole M. Lodise, Veronica Vernon, Rebecca H. Stone, Kylie N. Barnes, Cortney M. Mospan, and Nicole E. Cieri-Hutcherson
Subjects: Scope of practice, medicine.medical_treatment, Teaching method, education, Pharmacist, Pharmacy, Review, Pharmacists, Hormonal Contraception, Health Services Accessibility, Education, Contraceptive Agents, medicine, Humans, Emergency contraception, General Pharmacology, Toxicology and Pharmaceutics, Students, Curriculum, Medical education, business.industry, General Medicine, United States, Student pharmacist, Hormonal contraception, Education, Pharmacy, business, Psychology
Abstract: In 2014, the pharmacist's role in the United States expanded to include prescribing hormonal contraception, and this practice is currently addressed by policy in 14 states and the District of Columbia. Training and education requirements for this expanded scope of practice vary between states and are changing rapidly. The objective of this review is to examine how student pharmacists are taught to provide contraceptive care, specifically for prescribing ongoing hormonal contraception and emergency contraception, and to identify potential gaps in the United States pharmacy curricula related to contraception. Despite steady adoption into community pharmacy practice, there is sparse literature assessing educational methods used to teach contraceptive care. This review offers recommendations to promote consistent and comprehensive student pharmacist education in providing contraceptive care across institutions, regardless of state policy status.
Published: 2022

47. Glucocorticoid toxicity reduction with mepolizumab using the Glucocorticoid Toxicity Index

Author: Louise Dunn, Kirsty Honeyford, Liam G Heaney, Claire A. Butler, Yuqing Zhang, R Jayne Logan, P Jane McDowell, John H. Stone, and Lorcan McGarvey
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, business.industry, Minimal clinically important difference, Toxicity reduction, Antibodies, Monoclonal, Humanized, Asthma, Interquartile range, Internal medicine, Original Research Articles, Toxicity, medicine, Prednisolone, Humans, Anti-Asthmatic Agents, Prospective Studies, Prospective cohort study, business, Mepolizumab, Glucocorticoids, Glucocorticoid, medicine.drug
Abstract: Background Reduction in glucocorticoid exposure is the primary benefit of new biologic treatments in severe asthma, but there is currently no evidence that reduction in glucocorticoid exposure corresponds to a proportionate reduction in associated toxicity. Objectives To use the validated Glucocorticoid Toxicity Index (GTI) to assess change in glucocorticoid toxicity after 12 months treatment with mepolizumab, and compare toxicity change to glucocorticoid reduction and change in patient-reported outcome measures (PROMs). Methods A longitudinal, real-world prospective cohort of 101 consecutive patients with severe asthma commenced on mepolizumab in a specialist UK regional severe asthma clinic. GTI toxicity assessment, cumulative glucocorticoid exposure and PROMs were recorded on commencing mepolizumab (V1), and after 12 months treatment (V2). Results There was significant reduction in oral glucocorticoid exposure (V1 median 4280 mg prednisolone per year (interquartile range 3083–5475 mg) versus V2 2450 mg prednisolone per year (1243–3360 mg), p, Anti-T2 biologics decrease glucocorticoid requirements in severe eosinophilic asthma, but glucocorticoid reduction does not correlate with glucocorticoid toxicity reduction in individuals. Assessment of glucocorticoid toxicity reduction is crucial when considering response to biologics. https://bit.ly/3goyIRd
Published: 2022
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48. Characterizing the Tapering Practices of United States and Canadian Raw Powerlifters

Author: Caleb D. Bazyler, Michael H. Stone, Iñigo Mujika, Hayden J Pritchard, S. Kyle Travis, and Jeremy A. Gentles
Subjects: Male, Canada, medicine.medical_specialty, Competition level, Weight Lifting, Demographics, business.industry, Posture, Repetition maximum, Resistance Training, Physical Therapy, Sports Therapy and Rehabilitation, Tapering, Squat, General Medicine, Bench press, United States, Exercise Therapy, Training intensity, Physical therapy, medicine, Humans, Female, Orthopedics and Sports Medicine, Muscle Strength, business
Abstract: Travis, SK, Pritchard, HJ, Mujika, I, Gentles, JA, Stone, MH, and Bazyler, CD. Characterizing the tapering practices of United States and Canadian raw powerlifters. J Strength Cond Res 35(12S): S26-S35, 2021-The purpose of this study was to characterize the tapering practices used by North American powerlifters. A total of 364 powerlifters completed a 41-item survey encompassing demographics, general training, general tapering, and specific tapering practices. Nonparametric statistics were used to assess sex (male and female), competition level (regional/provincial, national, and international), and competition lift (squat, bench press, and deadlift). The highest training volume most frequently took place 5-8 weeks before competition, whereas the highest training intensity was completed 2 weeks before competition. A step taper was primarily used over 7-10 days while decreasing the training volume by 41-50% with varied intensity. The final heavy (>85% 1 repetition maximum [1RM]) back squat and deadlift sessions were completed 7-10 days before competition, whereas the final heavy bench press session was completed
Published: 2021
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49. Sex‐, Race‐ and Ethnicity‐Based Differences in Thromboembolic Events Among Adults Hospitalized With COVID‐19

Author: Joseph E. Ebinger, Jocelyn M. Beach, Mark A. Creager, Pablo Martínez-Camblor, Bjoern D. Suckow, Sadia Ilyas, David H. Stone, Jesse A. Columbo, Philip P. Goodney, and Stanislav Henkin
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Ethnic group, Disease, race and ethnicity, Logistic regression, Race (biology), COVID‐19, Thromboembolism, Internal medicine, Ethnicity, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, Sex Distribution, thrombosis, SARS-CoV-2, business.industry, Racial Groups, COVID-19, Hispanic or Latino, Odds ratio, thromboembolic, medicine.disease, Thrombosis, United States, Hospitalization, women, sex, and gender, RC666-701, Pacific islanders, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Background Patients hospitalized with COVID‐19 have an increased risk of thromboembolic events. Whether sex, race or ethnicity impacts these events is unknown. We studied the association between sex, race, and ethnicity and venous and arterial thromboembolic events among adults hospitalized with COVID‐19. Methods and Results We used the American Heart Association Cardiovascular Disease COVID‐19 registry. Primary exposures were sex and race and ethnicity, as defined by the registry. Primary outcomes were venous thromboembolic events and arterial thromboembolic events. We used logistic regression for risk adjustment. We studied 21 528 adults hospitalized with COVID‐19 across 107 centers (54.1% men; 38.1% non‐Hispanic White, 25.4% Hispanic, 25.7% non‐Hispanic Black, 0.5% Native American, 4.0% Asian, 0.4% Pacific Islander, and 5.9% other race and ethnicity). The rate of venous thromboembolic events was 3.7% and was more common in men (4.2%) than women (3.2%; P P P =0.002), and in non‐Hispanic Black patients (5.0%) than other races and ethnicities (range, 2.3%–4.7%; P Conclusions Men and non‐Hispanic Black adults hospitalized with COVID‐19 are more likely to have venous and arterial thromboembolic events. These subgroups may represent at‐risk patients more susceptible to thromboembolic COVID‐19 complications.
Published: 2021
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50. Circulating autoreactive proteinase 3(+) B cells and tolerance checkpoints in ANCA-associated vasculitis

Author: Carol A. Langford, Paul A. Monach, Kristina M. Harris, Alvise Berti, Paul Brunetta, Robert Spiera, Jacques-Olivier Pers, Divi Cornec, E. William St. Clair, Peter Heeringa, Ulrich Specks, Philip Seo, Tobias Peikert, Sophie Hillion, Amber M. Hummel, Peter A. Merkel, Young Min Son, Nedra Chriti, Wayel H. Abdulahad, Fernando C. Fervenza, Jie Sun, Cees G. M. Kallenberg, John H. Stone, Eva M. Carmona, Guido Grandi, Translational Immunology Groningen (TRIGR), and Groningen Kidney Center (GKC)
Subjects: Male, Vasculitis, Autoimmune diseases, Immunology, BIOMARKERS, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoimmunity, medicine.disease_cause, Peripheral blood mononuclear cell, Flow cytometry, ACTIVATION, WEGENERS-GRANULOMATOSIS, Double-Blind Method, Memory B Cells, Proteinase 3, Medicine, Humans, cardiovascular diseases, RITUXIMAB, SPECIFICITY, biology, medicine.diagnostic_test, business.industry, RECOGNITION, MYELOPEROXIDASE, General Medicine, medicine.disease, Flow Cytometry, PR3, In vitro, Peripheral, Myeloperoxidase, ANTIBODIES, biology.protein, Female, AUTOANTIBODIES, Clinical Medicine, business, Peptide Hydrolases
Abstract: BACKGROUND Little is known about the autoreactive B cells in antineutrophil cytoplasmic antibody–associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3–reactive (PR3+) B cells. METHODS Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets). RESULTS The frequency of PR3+ B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%–6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%–5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%–2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3+ B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001). CONCLUSION This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells. Trial registration ClinicalTrials.gov NCT00104299. Funding The Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research.
Published: 2021

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