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2. Stochastic natural frequencies analysis of hybrid composites: A numerical approach.

Author

Thakkar, B. S. and Karsh, P. K.

Subjects
*HYBRID materials, *GLASS composites, *SHAPE memory alloys, *MONTE Carlo method, *COMPOSITE plates, *NICKEL-titanium alloys
Abstract

This manuscript covenant by means of the random natural rate of recurrence analysis of hybrid composite plate by employing the finite element (FE) based numerical approach. Shape memory alloy (Nitinol) in the form of rods will be inserted in glass epoxy composite plates to obtain the hybrid composites. An algorithm is resultant for vagueness quantification of accepted frequencies of the hybrid composite owing to uncertain disparity in the substance properties. This deterministic finite element code is verified with the preceding copy. The effects of degree of randomness and specific volume on the first three natural frequencies will be determined. Monte Carlo simulation will be coupled with finite element code to conduct the random analysis. The outcome demonstrates the key in parameters painstaking in the current learning have momentous possessions on the randomness of initial three accepted frequencies of plank hybrid composite plates. [ABSTRACT FROM AUTHOR]

Published
2023
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3. Trend, Prevalence, and Outcomes of Pulmonary Embolism Amongst Us Hospitalizations - National Estimate

Author

Regassa, H., primary, Sindu, D., additional, Jerry, M., additional, Patra, T., additional, Bag, S., additional, Puli, S., additional, Panghal, R., additional, Gujarathi, R., additional, Thakkar, B., additional, Hsieh, Y.-C., additional, Erva, S., additional, Patel, U., additional, Kpadenou, V., additional, Uma Dwarakanath, N., additional, Shanmugam, S.N., additional, and Kelangi, S., additional

Published
2023
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6. Development and validation of patients' surgical safety checklist.

Author

Harris, K, Søfteland, E, Moi, AL, Harthug, S, Ravnøy, M, Storesund, A, Jurmy, E, Thakkar, B, Haaverstad, R, Skeie, E, Valen, HW, Sevdalis, N, Haugen, AS, Harris, K, Søfteland, E, Moi, AL, Harthug, S, Ravnøy, M, Storesund, A, Jurmy, E, Thakkar, B, Haaverstad, R, Skeie, E, Valen, HW, Sevdalis, N, and Haugen, AS

Abstract

BACKGROUND: Poor uptake and understanding of critical perioperative information represent a major safety risk for surgical patients. Implementing a patient-driven surgical safety checklist might enhance the way critical information is given and increase patient involvement in their own safety throughout the surgical pathway. The aim of this study was to develop and validate a Surgical Patient Safety Checklist (PASC) for use by surgical patients. METHOD: This was a prospective study, involving patient representatives, multidisciplinary healthcare professionals and elective surgical patients to develop and validate PASC using consensus-building techniques in two Norwegian hospitals. A set of items intended for PASC were rated by patients and then submitted to Content Validation Index (CVI) analyses. Items of low CVI went through a Healthcare Failure Mode and Effect Analysis (HFMEA) Hazard Scoring process, as well as a consensus process before they were either kept or discarded. Reliability of patients' PASC ratings was assessed using Intraclass Correlation Coefficient analysis. Lastly, the face validity of PASC was investigated through focus group interviews with postoperative patients. RESULTS: Initial development of PASC resulted in a checklist consisting of two parts, one before (32 items) and one after surgery (26 items). After achieving consensus on the PASC content, 215 surgical patients from six surgical wards rated the items for the CVI analysis on a 1-4 scale and mostly agreed on the content. Five items were removed from the checklist, and six items were redesigned to improve PASCs' user-friendliness. The total Scale-level index/Average (S-CVI/Ave) before revision was 0.83 and 0.86 for pre- and post-operative PASC items, respectively. Following revision, these increased to 0.86 and 0.93, respectively. The PASC items reliability score was 0.97 (95% confidence interval 0.96 to 0.98). The qualitative assessment identified that patients who used PASC felt more in

Published
2022

7. Beyond opioid prescribing: Evaluation of a substance use disorder curriculum for OBGYN residents

Author

Jones, H.E., Martin, C.E., Johnson, E., Thakkar, B., Connolly, A.M., and Cox, L.

Abstract

Objective Amidst the current opioid crisis, there is a need for better integration of substance use disorder screening and treatment across specialties. However, there is no consensus regarding how to best instruct OBGYN trainees in the clinical skills related to opioid and other substance use disorders (SUD). Study objectives were (1) to assess the effectiveness a SUD curriculum to improve self-reported competence among OBGYN residents and (2) to explore its effectiveness to improve attending evaluations of residents clinical skills as well as its feasibility and acceptability from the resident perspective. Methods A pilot 3-session curriculum was developed and adapted to SUD screening and treatment which included readings, didactics, and supervised outpatient clinical experiences for OBGYN post-graduate year 1 (PGY-1) residents rotating through an integrated OBGYNSUD clinic. Eighteen residents completed pre and post clinical skills self-Assessments (SUD screening, counseling, referring, Motivational Interviewing) using an adapted Zwisch Rating Scale (range 1 5). Scores were compared between time points using paired t-Tests. Subsamples also (a) were evaluated by the attending on three relevant Accreditation Council for Graduate Medical Education Milestones (ACGME) milestone sets using the web-based feedback program, myTIPreport (n = 10) and (b) completed a qualitative interview (n = 4). Results All PGY-1s (18/18) across three academic years completed the 3-session SUD curriculum. Clinical skill self-Assessments improved significantly in all areas [SUD Screening (2.44 (0.98) vs 3.56 (0.62), p = 0.01); Counseling (1.81 (0.71) vs 3.56 (0.51), p = .01; Referring (2.03 (0.74) vs 3.17 (0.71), p = .01; Motivational Interviewing (1.94 (1.06) vs 3.33 (0.69), p = .01)]. Milestone set levels assigned by attending evaluations (n = 10) also improved. Qualitative data (n = 4) revealed high acceptability; all curriculum components were viewed positively, and feedback was provided (e.g., desire for more patient exposures). Conclusion A pilot SUD curriculum tailored for OBGYN PGY-1 residents that goes beyond opioid prescribing to encompass SUD management is feasible, acceptable and likely effective at improving SUD core clinical skills.

Published
2022
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9. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Author

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, Abulencia K, Arora S, Baker A, Bata IR, Beaudry M, Belle Isle J, Bilodeau N, Boivin MC, Bolduc H, Bourgeois S, Brons S, Cantor W, Chaussé I, Chhabra A, Chouinard G, Cleveland T, Dattani D, Deslongchamps F, Diodati J, Drouin K, Duchesne L, Fontaine S, d'Amours DG, Gervais B, Gosselin G, Graham J, Grover A, Gupta A, Haldane H, Hartleib M, Hickey L, Huynh T, Johnston J, Julien VE, Lachance P, Lake J, Lamontagne C, Lauzon C, Lepage S, Maheux K, Manyari D, Martin E, McPherson C, Mehta S, Michaud N, Kouz SM, Murphy G, OKeefe D, Otis R, Ouimet F, Pandey S, Peck C, Perkins L, Richert L, Robbins K, Robinson S, Cabau JR, Ross B, Roy C, Roy M, Roy A, Rupka D, Affaki GS, Saunders K, Savard D, Soucy D, St Amour E, Thiessen S, Vertes G, Vezina M, Vincelli G, Weisnagel SJ, Zadra R, Chen J, Chen Y, Dong X, Feng Y, Feng Z, Fu G, Han B, Hao Y, He Y, He Z, Hong T, Jia Z, Jiang T, Jiang J, Jiang X, Ke Y, Li Y, Li Z, Li W, Li X, Liu P, Liu Y, Liu B, Liu S, Liu L, Lu Z, Lv Y, Ma C, Ma G, Peng L, Qing L, Ren L, Sang X, Song M, Sun Z, Wang J, Wang Y, Wei J, Wu W, Wu J, Xu H, Yan J, Yang P, Yang K, Yao Z, Yaoqing H, Yuan Z, Zhai Z, Zhang J, Zhang Y, Zhao R, Zhou H, Accini Mendoza JL, Aparicio CV, Castillo T, Chaverra I, Conrado Y, Coronel J, Cotes C, Cuentas I, Cuervo A, Dussan MA, Echeverria L, Hernandez E, Ibarra J, Isaza D, Jimenez D, Lopez P, Manzur F, Mejia I, Mendoza Y, Molina DI, Patino JM, Rodriguez D, Rodriguez LM, Rodriguez SM, Sanchez Vallejo G, Luz Serrano H, Sotomayor A, Urina M, Vesga B, Yupanqui H, Akrap B, Busic N, Ciglenecki N, Cmrecnjak J, Fucak E, Gabor M, Jeric M, Jutrisa N, Kordic K, Planinc I, Popovic Z, Radeljic V, Sesto I, Sutalo K, Tusek S, Belohlavek J, Budkova J, Busak L, Capova L, Cech V, Cermak O, Coufalova Z, Cyprian R, Dedek V, Dedkova S, Ferkl R, Hanak P, Hanustiakova A, Homza M, Horackova K, Houra M, Iveta H, Kaiserova L, Kala P, Karel I, Kellnerova I, Koleckar P, Kreckova M, Krupicka J, Lorenc Z, Machova V, Malik J, Masarikova L, Matyasek I, Mikus M, Mikusova T, Ondrasik J, Otava M, Palubova L, Pavlickova L, Peterka M, Petrova I, Pokorna B, Povolny P, Radvan M, Reznakova S, Rickova Z, Roszkowska P, Rotreklova M, Samkova D, Skalicka H, Slechticka A, Sternthal P, Telekes P, Tesak M, Vesely P, Vesely J, Vins P, Vitovec M, Vodnansky P, Zidova M, Keba E, Laane E, Pool T, Randvee L, Ratnik E, Reimand M, Reinmets S, Rivis L, Siemann M, Stern M, Toom M, Vahula V, Apel T, Axthelm C, Ayasse D, Ayasse M, Baar M, Baeumer A, Bagi ES, Becker B, Binder A, Blankenberg S, Braun P, Johansen BB, Contzen C, Delfonso F, Denecke C, Dengler T, Donaubauer T, Eichinger G, Englmann E, Erhard M, Faghih M, Foerster A, Frankenstein L, Fuchs R, Furch G, Gaeb-Strasas B, Germann H, Giese C, Goette A, Gravenhorst-Muenter U, Haege R, Haenel T, Hagemann D, Hagenow A, Hanefeld M, Heider J, Heisters J, Hennig D, Hielscher S, Himpel-Boenninghoff A, Holscher A, Hornig M, Jeserich M, Kaczmarek N, Kanitz S, Kara YD, Khariouzov A, Kiefer R, Kiroglu K, Klamm M, Klein C, Korth-Wiemann B, Krapivsky A, Kuenzler J, Kuntzsch A, Landers B, Lappo M, Laube S, Leggewie S, Lehmann D, Lepp H, Lierse T, Lindner C, Luecke-Uzar M, Luedemann J, Marschke T, Maruzzo S, Mauersberger K, Maus O, Meinrich M, Meissner A, Moehring B, Muehlhaus J, Mueller S, Muenter KC, Muenzel T, Naumann R, Nebel J, Neumann J, Nuding S, Overhoff U, Papke B, Pencz I, Peter Y, Peukert AM, Radde I, Rau T, Regner S, Reichenbach D, Reimer D, Rinke A, Roettges R, Romanski A, Rummel R, Samer H, Sanuri M, Sarnighausen HE, Schäfer B, Scheibner T, Schermaul KH, Schindler A, Schlundt C, Schmidt E, Schmidt K, Schnabel A, Schoen N, Schorn K, Schroeder T, Schulenburg D, Schulz M, Schulze U, Schulze J, Schumacher M, Schwerin G, Schwerin M, Stadelmeier S, Stahl HD, Stahl A, Stockhausen J, Stockhausen G, Stoessel J, Stolze K, Stratmann M, Szymanowski N, Teschner AB, Teske A, Uecker C, Veit S, Voeller H, Walter I, Walter J, Walther I, Weber HG, Weimer J, Wichterich K, Wiebusch A, Willmerdinger M, Willner C, Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, Bhadade S, Bisne V, Bohra P, Raghu C, Chauhan D, Chauhan H, Chavada J, Chaware G, Chella S, Chintala P, Dash D, Desai D, Devasia T, Dhanak R, Dobariya H, Dudhatra N, Duhan S, Fulwani M, Ghondale N, Ghosh S, Gohel P, Govindaraj D, Goyal B, Goyal S, Gundala AK, Gupta M, Hardas S, Iby M, Jagtap P, Jain A, Joshi U, Karpuram M, Kaur H, Khan A, Khan R, Kodem DR, Koeitti P, Kulkarni L, Kullal P, Kumar KS, Kumbla M, Latheef K, Lohkare M, Santosh MJ, Makhe B, Mandati M, Mehta A, Minocha G, Mittal A, Modi R, Mohan K, Oomman A, Pai R, Pai V, Palaniswami N, Pansheriya A, Parekh N, Patel J, Patel R, Patole T, Praveen M, Radhakrishnan V, Rajan B A, Rajasekhar D, Rao M, Rao MB, Rao NM, Rathnavel S, Rathore A, Rathore SRS, Rawat S, Reddy NC, Sarma R, Sathe S, Shah J, Shaikh P, Sharma K, Sharma S, Sharma T, Shetty P, Sidhu G, Singh V, Sohi GS, Srinath VS, Raju SS, Taran A, Thakkar B, Velusamy K, Vijan V, Vora V, Vuriya AK, Agosta GF, Antonicelli R, Ardissino D, Argiolas G, Baldin MG, Benedetti G, Berti S, Bevilacqua MT, Bolognesi MG, Dessalvi CC, Calabrese A, Campanale EG, Candusso R, Caso P, Cosmi F, Crea F, Crocamo A, De Caterina R, De Rosa S, Destro M, Di Biase M, Dognini GP, Eleuteri E, Fedele F, Ferrario M, Gabrielli D, Gamba C, Ganau A, Gravellone M, Iannopollo G, Indolfi C, Infusino F, Invitti C, Landolfi A, Lembo G, Liberato NL, Mannucci E, Marino P, Mariottoni B, Marziali A, Mercuro G, Monti L, Mos L, Mureddu V, Musumeci MB, Panzarino C, Parente A, Perotti M, Filardi PP, Petrillo C, Piatti P, Priori S, Racca V, Ragghianti B, Renda G, Righini V, Sarcone M, Senni M, Soro E, Tamburrini P, Vallone L, Villani GQ, Volpe M, Ajioka M, Akai Y, Ashino K, Baden M, Doi M, Eki Y, Endo T, Fukuike C, Hagiwara Y, Hasegawa K, Higuchi Y, Higuchi T, Hioki M, Hirayama A, Hiroma J, Hosokawa S, Ichisawa M, Iijima T, Inada T, Inagaki M, Ito K, Kaigawa K, Kajihara S, Kamiya H, Kamiya J, Kaneno Y, Katahira K, Kataoka M, Kawai M, Kawasaki T, Kojima E, Komura Y, Kuramochi T, Kuruma T, Kyo E, Mani H, Miyamoto T, Morii I, Morinaga Y, Morisawa T, Nagai Y, Naka T, Nakamura Y, Nakamura S, Nakayoshi K, Nishibe A, Ogawa M, Okada Y, Okawa M, Sakamoto Y, Sakurada M, Sasaki S, Seki S, Shimomura H, Shinozaki T, Sugimoto N, Suzuki A, Taguchi S, Takahashi J, Takase S, Tanabe K, Tanaka A, Tani S, Tomioka J, Tsuboi H, Tsuji M, Tsujita K, Tsujiyama S, Umesu A, Yamada T, Yamaguchi E, Yamamoto H, Yamamoto T, Yamane M, Yanase T, Yasuoka S, Yasutake M, Yokoyama M, Yoshida M, Yoshimoto E, Yunoki C, Balode A, Dormidontova G, Flaksa I, Nagele-Luse I, Rancane G, Sime I, Bartuseviciene S, Cepinskiene L, Dobilas V, Grigaraviciene I, Marcinkeviciene J, Mazutavicius R, Miliuniene R, Motiejuniene R, Norkiene S, Norkute-Macijauske U, Rudys A, Slapikas R, Stonkute K, Strazdiene D, Tijuneliene E, Urbonas G, Vanagiene S, Viezelis M, Arenas Leon JL, Bayram E, Carrillo J, Davalos C, De Los Rios M, Delgadillo T, Hernández N, Leon S, Mendoza N, Muñoz W, Ramos G, Anneveldt A, Bakker H, Brouwer M, Bunschoten P, De Boer P, De Jong C, De Vos A, Den Hartog F, Doesborg L, Dommerholt R, Drost I, Ellenbroek D, Engelen W, Folkeringa RJ, Hamer BJB, Herrman JP, Hoogslag PAM, Jansen M, Jerzewski A, Joosten C, Kalkman C, Kietselaer B, Kok M, Kooiman E, Kose V, Lardinois R, Lenderink T, Lok DJA, Lousberg A, Meijlis P, Mulder R, Singerling M, Smeele F, Stroes E, Swart HP, Ten Holt W, Van Der Wal M, Van Der Zwaan C, Van Kempen WW, Van Maarseveen M, Van Stein I, Viergever EP, Visseren FLJ, Voors C, Nugteren SKZ, Ata B, Berulfsen A, Rønnevik TD, Dickstein K, Furuseth B, Grundtvig M, Hansen H, Hofsoey K, Høivik HO, Bøen RH, Hurtig U, Pettersen KI, Johansen E, Kleve R, Kolleroy C, Moen S, Nilsen V, Norin V, Otterstad JE, Risberg K, Rønnevik P, Sirnes PA, Skjelvan G, Strand S, Szacinski G, Vegsundvåg J, Alcalde JM, Gomez Sanchez J, Rodriguez J, Rodriguez A, Zena N, Baszak J, Cymerman K, Czerski T, Fratczak M, Jaguszewska G, Kawka-Urbanek T, Koba M, Kopaczewski J, Kopczyńska M, Laniec M, Lysek R, Sciborski R, Szpajer M, 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A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, 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M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, c-reactive protein, Randomized controlled trial, law, Cardiovascular Disease, middle aged, double-blind method, antibodies, Myocardial infarction, humans, Stroke, interleukin-1beta, biology, Antibodies, Monoclonal, drug, General Medicine, Lipid, Aged, anti-inflammatory agents, monoclonal, humanized, atherosclerosis, cardiovascular diseases, dose-response relationship, female, incidence, infections, lipids, male, myocardial infarction, neutropenia, secondary prevention, stroke, Anti-Inflammatory Agent, aged, Editorial, Atherosclerosi, Monoclonal, Human, medicine.drug, medicine.medical_specialty, Neutropenia, Antibodies, Monoclonal, Humanized, Infections, Placebo, antibodies, monoclonal, dose-response relationship, drug, infection, medicine (all), 03 medical and health sciences, Internal medicine, medicine, Dose-Response Relationship, Drug, business.industry, Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease, C-reactive protein, medicine.disease, Surgery, Canakinumab, 030104 developmental biology, biology.protein, business
Abstract

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Published
2017
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11. Adhesion at polymer interfaces and pressure sensitive adhesive tapes

Author

Pocius, A.V., Kinning, D.J., Yarusso, D.J., Tirell, M., Thakkar, B., and Mangipudi, V.S.

Subjects
Adhesive tape -- Research, Polymers -- Research, Business, Chemicals, plastics and rubber industries, Chemistry, Research
Abstract

SPE's New Technology Committee examines current areas of research in the field of plastics science and technology. The following article, which is part of a series of presentations organized by [...]

Published
1997

12. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

Author

Farr, O.M. Sofopoulos, M. Tsoukas, M.A. Dincer, F. Thakkar, B. Sahin-Efe, A. Filippaios, A. Bowers, J. Srnka, A. Gavrieli, A. Ko, B.-J. Liakou, C. Kanyuch, N. Tseleni-Balafouta, S. Mantzoros, C.S.

Abstract

Aims/hypothesis: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods: In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrolment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (functional MRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results: Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation: For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. Trial registration: ClinicalTrials.gov NCT01562678 Funding: The study was funded by Novo Nordisk, NIH UL1 RR025758 and 5T32HD052961. © 2016, Springer-Verlag Berlin Heidelberg.

Published
2016

13. Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea

Author

Garg, R., Shankar, R., Thakkar, B., Kudapa, H., Krishnamurthy, L., Mantri, N., Varshney, R.K., Bhatia, S., Jain, M., Garg, R., Shankar, R., Thakkar, B., Kudapa, H., Krishnamurthy, L., Mantri, N., Varshney, R.K., Bhatia, S., and Jain, M.

Abstract

Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea.

Published
2016

18. International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

Author

Dodd, C.N. (Caitlin), Romio, S.A. (Silvana), Black, S. (Steve), Vellozzi, C. (Claudia), Andrews, N.J. (Nick), Sturkenboom, M.C.J.M. (Miriam), Zuber, P. (Patrick), Hua, W. (Wei), Bonhoeffer, J. (Jan), Buttery, J. (Jim), Crawford, N. (Nigel), Deceuninck, G. (Genevieve), Vries, C.S. (Corinne) de, Wals, P. (Philippe) de, Gimeno, D. (David), Heijbel, H. (Harald), Hughes, H. (Hayley), Hur, K. (Kwan), Hviid, A. (Anders), Kelman, J. (Jeffrey), Kilpi, T. (Tehri), Chuang, S.K. (S.), Macartney, T. (Thomas), Rett, M. (Melisa), Lopez-Callada, V.R. (Vesta Richardson), Salmon, D. (Daniel), Sanchez, F.G. (Francisco Gimenez), Sanz, N. (Nuria), Silverman, B. (Bernard), Storsaeter, J. (Jann), Thirugnanam, U. (Umapathi), Maas, N.A.T. (Nicoline) van der, Yih, K. (Katherine), Zhang, T. (Teng Fei), Izurieta, H.S. (Hector), Addis, B.J., Akhtar, A. (Aysha), Cope, J. (Judith), Davis, R.L. (Robert), Gargiullo, P. (Paul), Kurz, X. (Xavier), Law, B. (Barbara), Sahinovic, I. (Isabelle), Tokars, J. (Jerry), Serrano, P. (Pedro), Cheng, A. (Aixin), Charles, P. (Pat), Clothier, H. (Hazel), Day, B. (Bruce), Day, T. (Timothy), Gates, P. (Peter), MacDonnell, R. (Richard), Roberts, L. (Les), Rodriguez-Casero, V. (Vic-toria), Wijeratne, T. (Tissa), Kiers, H.A.L. (Henk), Blyth, C. (Christopher), Booy, R. (Robert), Elliott, E. (Elizabeth), Gold, M.R. (Michael), Marshall, H., McIntyre, P. (Peter), Richmond, P. (Peter), Royle, J. (Jenny), Wood, N.W. (Nicholas), Zurynski, Y. (Yvonne), Calvo, G. (Gonzalo), Campins, M. (Magda), Corominas, N. (Nuria), Torres, F. (Ferran), Valls, V., Vilella, A. (Ángels), Dutra, A. (Amalia), Eick-Cost, A. (Angelia), Jackson, H.M. (Henry), Garman, K. (Katherine), Hu, Z. (Zheng), Rigo, J., Badoo, J. (Judith), Cho, D (David), Polakowski, L.L. (Laura), Sandhu, S.K. (Sukhminder), Sun, G. (Guoying), Chan, H.-S.S. (Hoi-Shan Sophelia), Chan, K.-Y. (Kwok-Yin), Cheung, R. (Raymond), Cheung, Y-F. (Yuk-Fai), Cherk, S. (Sharon), Chuang, S.K (S.), Fok, D. (Dennis), Fung, B.-H. (Bun-Hey), Ko, K.-F. (Kwai-Fu), Lau, K.W. (Ka Wing), Lau, K.-K. (Kwok-Kwong), Li, P. (Pulin), Liu, H.-T. (Hui-Tung), Liu, S.-H. (Shao-Haei), Mok, K. (Kin), So, J. (Joanna), Wong, W. (Winnie), Wu, S.-P. (Shun-Ping), Ball, R. (Robert), Burwen, D. (Dale), Franks, R.L. (Riley), Gibbs, J.M. (Jonathan), Kliman, R.E. (Rebecca), Kropp, S. (Silke), MaCurdy, T.E. (Thomas), Martin, D.B. (David), Sandhu, S.-D.K. (Sukhmin-Der), Worrall, B.B. (Bradford B.), Fuentes, D.E.F. (Dra. Elvira Fuentes), González, P.C.O. (Paola Carolina Ojeda), Reyna, V.F. (Valerie ), Kulldorff, M. (Martin), Lee, G. (Grace), Lieu, T.A. (Tracy), Platt, S., Serres, G.D. (Gaston De), Jabin, K. (Kamilah), Soh, B.L.S. (Bee Leng Sally), Arnheim-Dahlström, L. (Lisen), Castot, A. (Anne), Melker, H.E. (Hester) de, Dieleman, J.P. (Jeanne), Hallgren, J. (Jonal), Jacobs, B.C. (Bart), Johansen, K. (Kari), Kramarz, P (Piotr), Lapeyre, M. (Maryse), Leino, T. (Tuija), Mølgaard-Nielsen, D. (Ditte), Mosseveld, M. (Mees), Olberg, H.K. (Henning K), Sammon, C.-M. (Cor-Mac), Saussier, C. (Christel), Schuemie, M.J. (Martijn), Sommet, A. (Agnès), Sparen, P. (Pär), Svanström, H. (Henrik), Vanrolleghem, A.M. (Ann M.), Weibel, D.M. (Daniel), Domingo, J.D. (Javier Diez), Esparza, J.L. (José LuísMicó), Lucas, R.M.O. (Rafael M. Ortí), Maseres, J.B.M. (Juan B. Mollar), Sánchez, J.L.A. (José Luís Alfonso), Sánchez, M.G. (Mercedes Garcés), Viguer, V.Z. (Vicente Zanón), Cunningham, F. (Francesca), Avagyan, A. (Armen), Thakkar, B. (Bharat), Zhang, R. (Rongping), Dodd, C.N. (Caitlin), Romio, S.A. (Silvana), Black, S. (Steve), Vellozzi, C. (Claudia), Andrews, N.J. (Nick), Sturkenboom, M.C.J.M. (Miriam), Zuber, P. (Patrick), Hua, W. (Wei), Bonhoeffer, J. (Jan), Buttery, J. (Jim), Crawford, N. (Nigel), Deceuninck, G. (Genevieve), Vries, C.S. (Corinne) de, Wals, P. (Philippe) de, Gimeno, D. (David), Heijbel, H. (Harald), Hughes, H. (Hayley), Hur, K. (Kwan), Hviid, A. (Anders), Kelman, J. (Jeffrey), Kilpi, T. (Tehri), Chuang, S.K. (S.), Macartney, T. (Thomas), Rett, M. (Melisa), Lopez-Callada, V.R. (Vesta Richardson), Salmon, D. (Daniel), Sanchez, F.G. (Francisco Gimenez), Sanz, N. (Nuria), Silverman, B. (Bernard), Storsaeter, J. (Jann), Thirugnanam, U. (Umapathi), Maas, N.A.T. (Nicoline) van der, Yih, K. (Katherine), Zhang, T. (Teng Fei), Izurieta, H.S. (Hector), Addis, B.J., Akhtar, A. (Aysha), Cope, J. (Judith), Davis, R.L. (Robert), Gargiullo, P. (Paul), Kurz, X. (Xavier), Law, B. (Barbara), Sahinovic, I. (Isabelle), Tokars, J. (Jerry), Serrano, P. (Pedro), Cheng, A. (Aixin), Charles, P. (Pat), Clothier, H. (Hazel), Day, B. (Bruce), Day, T. (Timothy), Gates, P. (Peter), MacDonnell, R. (Richard), Roberts, L. (Les), Rodriguez-Casero, V. (Vic-toria), Wijeratne, T. (Tissa), Kiers, H.A.L. (Henk), Blyth, C. (Christopher), Booy, R. (Robert), Elliott, E. (Elizabeth), Gold, M.R. (Michael), Marshall, H., McIntyre, P. (Peter), Richmond, P. (Peter), Royle, J. (Jenny), Wood, N.W. (Nicholas), Zurynski, Y. (Yvonne), Calvo, G. (Gonzalo), Campins, M. (Magda), Corominas, N. (Nuria), Torres, F. (Ferran), Valls, V., Vilella, A. (Ángels), Dutra, A. (Amalia), Eick-Cost, A. (Angelia), Jackson, H.M. (Henry), Garman, K. (Katherine), Hu, Z. (Zheng), Rigo, J., Badoo, J. (Judith), Cho, D (David), Polakowski, L.L. (Laura), Sandhu, S.K. (Sukhminder), Sun, G. (Guoying), Chan, H.-S.S. (Hoi-Shan Sophelia), Chan, K.-Y. (Kwok-Yin), Cheung, R. (Raymond), Cheung, Y-F. (Yuk-Fai), Cherk, S. (Sharon), Chuang, S.K (S.), Fok, D. (Dennis), Fung, B.-H. (Bun-Hey), Ko, K.-F. (Kwai-Fu), Lau, K.W. (Ka Wing), Lau, K.-K. (Kwok-Kwong), Li, P. (Pulin), Liu, H.-T. (Hui-Tung), Liu, S.-H. (Shao-Haei), Mok, K. (Kin), So, J. (Joanna), Wong, W. (Winnie), Wu, S.-P. (Shun-Ping), Ball, R. (Robert), Burwen, D. (Dale), Franks, R.L. (Riley), Gibbs, J.M. (Jonathan), Kliman, R.E. (Rebecca), Kropp, S. (Silke), MaCurdy, T.E. (Thomas), Martin, D.B. (David), Sandhu, S.-D.K. (Sukhmin-Der), Worrall, B.B. (Bradford B.), Fuentes, D.E.F. (Dra. Elvira Fuentes), González, P.C.O. (Paola Carolina Ojeda), Reyna, V.F. (Valerie ), Kulldorff, M. (Martin), Lee, G. (Grace), Lieu, T.A. (Tracy), Platt, S., Serres, G.D. (Gaston De), Jabin, K. (Kamilah), Soh, B.L.S. (Bee Leng Sally), Arnheim-Dahlström, L. (Lisen), Castot, A. (Anne), Melker, H.E. (Hester) de, Dieleman, J.P. (Jeanne), Hallgren, J. (Jonal), Jacobs, B.C. (Bart), Johansen, K. (Kari), Kramarz, P (Piotr), Lapeyre, M. (Maryse), Leino, T. (Tuija), Mølgaard-Nielsen, D. (Ditte), Mosseveld, M. (Mees), Olberg, H.K. (Henning K), Sammon, C.-M. (Cor-Mac), Saussier, C. (Christel), Schuemie, M.J. (Martijn), Sommet, A. (Agnès), Sparen, P. (Pär), Svanström, H. (Henrik), Vanrolleghem, A.M. (Ann M.), Weibel, D.M. (Daniel), Domingo, J.D. (Javier Diez), Esparza, J.L. (José LuísMicó), Lucas, R.M.O. (Rafael M. Ortí), Maseres, J.B.M. (Juan B. Mollar), Sánchez, J.L.A. (José Luís Alfonso), Sánchez, M.G. (Mercedes Garcés), Viguer, V.Z. (Vicente Zanón), Cunningham, F. (Francesca), Avagyan, A. (Armen), Thakkar, B. (Bharat), and Zhang, R. (Rongping)

Abstract

Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. Results: We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1

Published
2013
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19. Neonatal Exposure to Melatonin Favours Follicular Survival and Increases Fecundity in the Female Rat

Author

Thakkar, B. P., Ramachandran, A. V., Thakkar, B. P., and Ramachandran, A. V.

Abstract

Rat neonates have been exposed to melatonin by i.p. injection of 40(19 melatonin/animal/day daily in the evening at 16:30 hrs from day 0 to day 21. The preweaning hypeimelatonemia did not significantly influence either adult body weight or ovarian weight. The estrogen titre was reduced and progesterone titre increased in melatonin treated rats. Increased thyroid weight and elevated thyroid hormones levels were also recorded. The primordial and primary follicles were more in number with significantly lesser atretic follicles of all developmental stages. The first litter size was significantly greater (lit 3 vs 8 ± 2) in melatonin treated rats compared to controls. These results are interpreted in terms of protective action of neonatal melatonin against follicular apoptosis either directly or indirectly through thyroid hormones.

Published
2005

24. Experimental and numerical investigation of creasing in corrugated paperboard.

Author

Thakkar, B. K., Gooren, L. G. J., Peerlings, R. H. J., and Geers, M. G. D.

Subjects
*CORRUGATED paperboard, *DEFORMATIONS (Mechanics), *NUMERICAL analysis, *MATHEMATICAL analysis, *RHEOLOGY
Abstract

Creasing is a process which indents a section of corrugated board along fold lines to facilitate a neat fold. The most common failure site in a box made out of corrugated board is at the folds, where the stiffness is reduced by the creasing operation. Crease depth is an important parameter to be controlled. If the crease is too shallow, the section will crack during folding due to excessive strain on the outer liner. On the other hand, if the crease is too deep, the board may crack during the creasing operation itself or it may fail during handling due to excessive reduction in local strength along the fold line. A review of the literature reveals that only a limited amount of research has been carried out on experimental creasing of corrugated boards and comparison with numerical analyses. However, modelling of paper for corrugated board has been successfully done using Hill's plasticity model. In this work, experimental investigations on creasing of corrugated paperboard are carried out. These are complemented by finite element simulations of the creasing process. The simulations are found to be in good agreement with the experimental results. The findings of the work done are helpful in understanding the mechanics of creasing more clearly and in arriving at an appropriate crease depth in order to reduce cracking of corrugated board during the creasing process. [ABSTRACT FROM AUTHOR]

Published
2008
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28. Ciprofloxacin versus amoxycillin/clavulanic acid in the treatment of urinary tract infections in general practice.

Author

Abbas, A. M. A., Chandra, V., Dongaonkar, P. P., Goel, P. K., Kacker, P., Patel, N. A., Shrivastava, O. P., Thakkar, B., Tillotson, G. S., and Abbas, A M

Abstract

An open, randomized general practice study was performed to assess the comparative efficacy and tolerability of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of uncomplicated urinary tract infection. One hundred and eighty nine patients were recruited into the study. In comparison of pre- and post-treatment urine cultures and symptomatology, ciprofloxacin was significantly more effective (P less than 0.01) than amoxycillin/clavulanic acid. Both drugs were well tolerated with minimal adverse side effects. Ciprofloxacin is an effective and safe treatment for uncomplicated urinary tract infection in general practice. [ABSTRACT FROM AUTHOR]

Published
1989

29. New method to measure TAN of crude oil and refinery distillation fractions.

Author

MCGARVEY, B., MCGARVEY, C. E., THAKKAR, B., TUCKER, L., and SPAFFORD, L.

Subjects
CORROSION in petroleum refineries, SHEARING force, INDUSTRIAL equipment, NAPHTHENIC acids, FRACTIONAL distillation
Abstract

The article discusses new method to measure total acid number (TAN) of crude oil and refinery distillation fractions. It mentions that naphthenic acid-containing crudes increase the risk of experiencing high temperature corrosion of equipment in refinery operations. It also reveals that flow-induced wall shear stress can influence the corrosion by naphthenic acid and sulfur species.

Published
2017

30. Antiinflammatory therapy with canakinumab for atherosclerotic disease

Author

Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., Kultursay H., Bilazarian S., East C., Forgosh L., Harris B., Ligueros M., Bohula E., Charmarthi B., Cheng S., Chou S., Danik J., McMahon G., Maron B., Ning M., Olenchock B., Pande R., Perlstein T., Pradhan A., Rost N., Singhal A., Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., Cosgrove S., Levine D., Lopes R., Scott J., Hilkert R., Tamesby G., Mickel C., Manning B., Woelcke J., Tan M., Manfreda S., Ponce T., Kam J., Saini R., Banker K., Salko T., Nandy P., Tawfik R., O’Neil G., Manne S., Jirvankar P., Lal S., Nema D., Jose J., Collins R., Bailey K., Blumenthal R., Colhoun H., Gersh B., Abreu M., Actis M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., Hominal M., Ibañez J., Jure H., Jure D., Vico M.L., Liniado G., Luciardi H., Luquez H., Maehara G., Maffei L., Majul C., Mallagray M., Marinaro S., Martinez J., Massaccesi R., De Los Milagros Had M., Azize G.M., Montana O., Montenegro E., Morell Y., Muntaner J., Navarrete S., Olmedo M., Paganini M., Paz S., Perez Manghi F., Piskorz D., Polato C., Recoaro R., Romano A., Salinger M., Sanchez A., Saravia M.A., Sarjanovich R., Scaro G., Schiavi L.B., Soler J., Tinnirello V., Tomassi A., Valle M., Vallejo M.A., Venturini C., Marcela Wenetz L.M., Yossen M., Zaidman C., Zalazar L., Zangroniz P., Amerena J., Brady L., Colquhoun D., Eccleston D., Ferreira-Jardim A., French J., Jayasinghe R., Mcintosh C., Ord M., Plotz M., Purnell P., Roberts-Thomson P., Schultz C., Shanahan T., Tan R., Taverner P., Turner F., Vibert J., Vorster M., William M., Youssef G., Bergler-Klein J., Brath H., Brodmann M., Fliesser-Goerzer E., Haider K., Heeren G., Hiden C., Mandic L., Paulweber B., Ploechl A., Prenner A., Steringer-Mascherbauer R., Strohner-Kaestenbauer H., Barbato E., Bouvy C., Briké C., Charlier F., Cools F., De Knijf K., De Wolf L., Delforge M., Deweerdt N., Gits F., Goffinet C., Hermans K., Hollanders G., Mestdagh I., Pirenne B., Servaes V., Simons N., Tahon S., Theunissen E., Van Genechten G., Vervoort G., Vissers C., Vranckx P., Vrolix M., Abib E.Jr., Abrantes J., Araujo Fonseca M., Barbosa E., Barroso W., Barroso A., Bodanese L., Botelho R., Costa Amorim R., Da Costa F., Da Silva A., Da Silva O.Jr., Da Silva D.Jr., Ferreira Dos Santos T., Dos Santos F., Dos Santos A., Duda N., Feitosa G., Felario Junior GA., Ferraz R., Filho P., Fonseca A., Wanderley F.F., Freitas E., Fucci F., Marengo Garcia De Carvalho L., Hernandez M., Hettwer Magedanz E., Julião K., Kormann A., Lameira A., Lima F., Lino E., Maia L., Manenti E., Marchi A.L., Fischer S.M., Michalaros Y., Moraes J.Jr., Moreira L., Pagnan M., Pesce F., Pinheiro L., Rassi S., Reis G., Reis H., Resende I., Roel A., Ruschel K., Saporito W., Saraiva J.F., Seroqui M., Silva R., Unterkircher B., Vicente C., Vieira N., Xavier J.P., Zucchetti C., Angelova I., Dimitrov G., Genova D., Gospodinov K., Goudev A., Grigorova V., Hristova K., Makedonska J.J., Katova T., Kostov K., Lazov P., Manov E., Manukov I., Manukov D., Milanova M., Kabakchieva V.M., Petrov D., Petrusheva T., Pramatarova I., Raev D., Runev N., Sirakova-Taseva A., Tisheva-Gospodinova S., Todorova A., Tzekova M., Yakovova S., Yanev T., Abulencia K., Arora S., Baker A., Bata I.R., Beaudry M., Belle Isle J., Bilodeau N., Boivin M.C., Bolduc H., Bourgeois S., Brons S., Cantor W., Chaussé I., Chhabra A., Chouinard G., Cleveland T., Dattani D., Deslongchamps F., Diodati J., Drouin K., Duchesne L., Fontaine S., D'Amours D.G., Gervais B., Gosselin G., Graham J., Grover A., Gupta A., Haldane H., Hartleib M., Hickey L., Huynh T., Johnston J., Julien V.E., Lachance P., Lake J., Lamontagne C., Lauzon C., Lepage S., Maheux K., Manyari D., Martin E., McPherson C., Mehta S., Michaud N., Kouz S.M., Murphy G., OKeefe D., Otis R., Ouimet F., Pandey S., Peck C., Perkins L., Richert L., Robbins K., Robinson S., Cabau J.R., Ross B., Roy C., Roy M., Roy A., Rupka D., Affaki G.S., Saunders K., Savard D., Soucy D., St Amour E., Thiessen S., Vertes G., Vezina M., Vincelli G., Weisnagel S.J., Zadra R., Chen J., Chen Y., Dong X., Feng Y., Feng Z., Fu G., Han B., Hao Y., He Y., He Z., Hong T., Jia Z., Jiang T., Jiang J., Jiang X., Ke Y., Li Y., Li Z., Li W., Li X., Liu P., Liu Y., Liu B., Liu S., Liu L., Lu Z., Lv Y., Ma C., Ma G., Peng L., Qing L., Ren L., Sang X., Song M., Sun Z., Wang J., Wang Y., Wei J., Wu W., Wu J., Xu H., Yan J., Yang P., Yang K., Yao Z., Yaoqing H., Yuan Z., Zhai Z., Zhang J., Zhang Y., Zhao R., Zhou H., Accini Mendoza JL., Aparicio C.V., Castillo T., Chaverra I., Conrado Y., Coronel J., Cotes C., Cuentas I., Cuervo A., Dussan M.A., Echeverria L., Hernandez E., Ibarra J., Isaza D., Jimenez D., Lopez P., Manzur F., Mejia I., Mendoza Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., Sanchez Vallejo G., Luz Serrano H., Sotomayor A., Urina M., Vesga B., Yupanqui H., Akrap B., Busic N., Ciglenecki N., Cmrecnjak J., Fucak E., Gabor M., Jeric M., Jutrisa N., Kordic K., Planinc I., Popovic Z., Radeljic V., Sesto I., Sutalo K., Tusek S., Belohlavek J., Budkova J., Busak L., Capova L., Cech V., Cermak O., Coufalova Z., Cyprian R., Dedek V., Dedkova S., Ferkl R., Hanak P., Hanustiakova A., Homza M., Horackova K., Houra M., Iveta H., Kaiserova L., Kala P., Karel I., Kellnerova I., Koleckar P., Kreckova M., Krupicka J., Lorenc Z., Machova V., Malik J., Masarikova L., Matyasek I., Mikus M., Mikusova T., Ondrasik J., Otava M., Palubova L., Pavlickova L., Peterka M., Petrova I., Pokorna B., Povolny P., Radvan M., Reznakova S., Rickova Z., Roszkowska P., Rotreklova M., Samkova D., Skalicka H., Slechticka A., Sternthal P., Telekes P., Tesak M., Vesely P., Vesely J., Vins P., Vitovec M., Vodnansky P., Zidova M., Keba E., Laane E., Pool T., Randvee L., Ratnik E., Reimand M., Reinmets S., Rivis L., Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., 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A., Mantas I., Megalou A., Milkas A., Nanas J., Olympios C.D., Patsilinakos S., Perperis A., Poulimenos L., Saloustros I., Tsioufis K., Tsorbatzoglou K., Vardas P., Zarifis I., Aguilar M., Arango J.L., Borrayo N.A., Corona V., Guerrero A., Guzman I., Haase F., De Krumbach L., Montenegro P., Munoz R., Munoz N., Paniagua A., Solares A., Vogel M., Anita S., Blazsek Z., Decsi K., Fulop T., Hangyal T., Hegedus V., Kalina A., Karakai H., Katona A., Kiss R.G., Kovacs A., Laszlo Z., Lupkovics G., Medvegy M., Merkely B., Mihaly N., Nagy A.C., Dékány J.N., Nikoletta P., Noori E., Penzes J., Poor F., Sarszegi Z., Simay A., Simon J., Szakal I., Szatmarine V., Szocs A., Zilahi Z., Karsai X.Z., Andersen K., Sigurdadottir E., Skuladottir F., Abdullakutty J., Abhaichand R., Abhyankar A., Agarwal D.K., Aggarwal R.K., Ahire N., Awasthi A.K., Babu R., Bai A., Bali H.K., Banker D., Bhadade S., Bisne V., Bohra P., Raghu C., Chauhan D., Chauhan H., Chavada J., Chaware G., Chella S., Chintala P., Dash D., Desai D., Devasia T., Dhanak R., Dobariya H., Dudhatra N., Duhan S., Fulwani M., Ghondale N., Ghosh S., Gohel P., Govindaraj D., Goyal B., Goyal S., Gundala A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., Makhe B., Mandati M., Mehta A., Minocha G., Mittal A., Modi R., Mohan K., Oomman A., Pai R., Pai V., Palaniswami N., Pansheriya A., Parekh N., Patel J., Patel R., Patole T., Praveen M., Radhakrishnan V., Rajan B A., Rajasekhar D., Rao M., Rao M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta G.F., Antonicelli R., Ardissino D., Argiolas G., Baldin M.G., Benedetti G., Berti S., Bevilacqua M.T., Bolognesi M.G., Dessalvi C.C., Calabrese A., Campanale E.G., Candusso R., Caso P., Cosmi F., Crea F., Crocamo A., De Caterina R., De Rosa S., Destro M., Di Biase M., Dognini G.P., Eleuteri E., Fedele F., Ferrario M., Gabrielli D., Gamba C., Ganau A., Gravellone M., Iannopollo G., Indolfi C., Infusino F., Invitti C., Landolfi A., Lembo G., Liberato N.L., Mannucci E., Marino P., Mariottoni B., Marziali A., Mercuro G., Monti L., Mos L., Mureddu V., Musumeci M.B., Novo S., Panzarino C., Parente A., Perotti M., Filardi P.P., Petrillo C., Piatti P., Priori S., Racca V., Ragghianti B., Renda G., Righini V., Sarcone M., Senni M., Soro E., Tamburrini P., Vallone L., Villani G.Q., Volpe M., Ajioka M., Akai Y., Ashino K., Baden M., Doi M., Eki Y., Endo T., Fukuike C., Hagiwara Y., Hasegawa K., Higuchi Y., Higuchi T., Hioki M., Hirayama A., Hiroma J., Hosokawa S., Ichisawa M., Iijima T., Inada T., Inagaki M., Ito K., Kaigawa K., Kajihara S., Kamiya H., Kamiya J., Kaneno Y., Katahira K., Kataoka M., Kawai M., Kawasaki T., Kojima E., Komura Y., Kuramochi T., Kuruma T., Kyo E., Mani H., Miyamoto T., Morii I., Morinaga Y., Morisawa T., Nagai Y., Naka T., Nakamura Y., Nakamura S., Nakayoshi K., Nishibe A., Ogawa M., Okada Y., Okawa M., Sakamoto Y., Sakurada M., Sasaki S., Seki S., Shimomura H., Shinozaki T., Sugimoto N., Suzuki A., Taguchi S., Takahashi J., Takase S., Tanabe K., Tanaka A., Tani S., Tomioka J., Tsuboi H., Tsuji M., Tsujita K., Tsujiyama S., Umesu A., Yamada T., Yamaguchi E., Yamamoto H., Yamamoto T., Yamane M., Yanase T., Yasuoka S., Yasutake M., Yokoyama M., Yoshida M., Yoshimoto E., Yunoki C., Balode A., Dormidontova G., Flaksa I., Nagele-Luse I., Rancane G., Sime I., Bartuseviciene S., Cepinskiene L., Dobilas V., Grigaraviciene I., Marcinkeviciene J., Mazutavicius R., Miliuniene R., Motiejuniene R., Norkiene S., Norkute-Macijauske U., Rudys A., Slapikas R., Stonkute K., Strazdiene D., Tijuneliene E., Urbonas G., Vanagiene S., Viezelis M., Arenas Leon JL., Bayram E., Carrillo J., Davalos C., De Los Rios M., Delgadillo T., Hernández N., Leon S., Mendoza N., Muñoz W., Ramos G., Anneveldt A., Bakker H., Brouwer M., Bunschoten P., De Boer P., De Jong C., De Vos A., Den Hartog F., Doesborg L., Dommerholt R., Drost I., Ellenbroek D., Engelen W., Folkeringa R.J., Hamer BJB., Herrman J.P., Hoogslag PAM., Jansen M., Jerzewski A., Joosten C., Kalkman C., Kietselaer B., Kok M., Kooiman E., Kose V., Lardinois R., Lenderink T., Lok DJA., Lousberg A., Meijlis P., Mulder R., Singerling M., Smeele F., Stroes E., Swart H.P., Ten Holt W., Van Der Wal M., Van Der Zwaan C., Van Kempen W.W., Van Maarseveen M., Van Stein I., Viergever E.P., Visseren FLJ., Voors C., Nugteren SKZ., Ata B., Berulfsen A., Rønnevik T.D., Dickstein K., Furuseth B., Grundtvig M., Hansen H., Hofsoey K., Høivik H.O., Bøen R.H., Hurtig U., Pettersen K.I., Johansen E., Kleve R., Kolleroy C., Moen S., Nilsen V., Norin V., Otterstad J.E., Risberg K., Rønnevik P., Sirnes P.A., Skjelvan G., Strand S., Szacinski G., Vegsundvåg J., Alcalde J.M., Gomez Sanchez J., Rodriguez J., Rodriguez A., Zena N., Baszak J., Cymerman K., Czerski T., Fratczak M., Jaguszewska G., Kawka-Urbanek T., Koba M., Kopaczewski J., Kopczyńska M., Laniec M., Lysek R., Sciborski R., Szpajer M., Torun A., Wujkowski M., Zielinski M., Ahn Y., Baek C., Bang S.A., Chang K., Choi A.J., Han S., Hyun K., Kim M., Kim K.S., Kim B., Lee S.H., Lee J., Lee H.N., Lee J.H., Moon K., Park B., Park C., Tahk S., Yim K.H., Yim S., Tase T., Andor M., Aron G., Badea C., Casoinic F., Clocotan M., Coman S., Emil B., Imre B.S., Istratoaie O., Liviu C., Maximov D., Militaru C., Minescu B., Istvan K.P., Parepa I., Petrescu L., Podoleanu C., Pop C.F., Popa V., Popescu E., Radoi M., Sarbu I., Socoteanu E., Socoteanu G., Sorodoc L., Spiridon M., Stanciulescu G., Stefanescu M., Tanaseanu C., Tudoran M., Zdrenghea D., Agafina A., Akatova E., Avdonina N., Balukova E., Barbarash O.L., Bartosh L., Boyarkin M., Bulashova O., Burova N., Churina S., Demidova M., Dorogova I., Dovgalevskiy Y., Dovgolis S., Dudarev M., Fitilev S., Gapon L., Gazizianova V., Gordeev I., Ivanov I., Izmozherova N., Kazanskay E., Khirmanov V., Khromtsova O., Konradi A., Kosmacheva E., Kozlova S., Kulibaba E., Kuzin A., Libov I., Lipchenko A., Lozhkina N., Malchikova S., Morozov E., Myslyaeva L., Onuchina E., Palatkina T., Panov A., Parmon E., Petelina T., Repin A., Reznik I., Sazonova E., Sergienko T., Shaposhnik I., Shapovalova Y., Shustov S., Shvarts Y., Skopets I., Skuratova M., Smolenskaya O., Solovev O., Trofimov V., Vasiliev M., Vezikova N., Vozzhaev A., Yakushin S., Zadionchenko V., Apostolovic S., Adjic N.C., Ilic I., Ilic S., Nikolic L., Pupic L., Stokuca-Korac N., Antalik L., Bugan V., Csala L., Dokupilova A., Dzupina A., Forgon T., Fulop P., Gonsorcik J., Gyorgyova E., Holoubek D., Horvat P., Kamensky G., Kolikova V., Krupciakova B., Lenner E., Lennerova J., Lukac J., Majercak I., Mancikova I., Micko K., Nociar J., Pales J., Palka J.Jr., Poliacik P., Ruffini L., Sabo L., Skubova K., Slanina M., Smik R., Srdos V., Stitova M., Stofkova D., Strbova J., Such S., Toth P., Urgeova L., Vinanska D., Zareczky P., Flezar M., Kovacic D., Marcun R., Zagozen P., Bolsmann C., Conradie C., Dawood S.Y., Decsi K.L., Ebrahim I., Henley L., Horak A., Kapp I., Komati S., Lock E., Maboyi S., Makotoko E., Manga P., Page A., Ramdas S., Ranjith N., Roos J., Talliard C., Ajax K., Al-Khalili F., Assarsson E., Bergholtz T., Blom K.B., Boman K., Boström P.A., Curiac D., Jensen E.D., Dahlen G., Davidsson K., Duckert A., Hansson A., Härstedt N., Henriksson A., Olsson G.H., Johansson K., Jonsson J.E., Knutsson A., Lindholm C.J., Lönnberg I., Lundqvist M., Mellberg L., Moodh J., Mooe T., Olofsson M., Risenfors M., Rönndahl M., Sundelin R., Suorra I., Torgersruud M., Torstensson I., Chen C.P., Chen Z.C., Chen M.H., Cheng S.M., Cheng J.J., Fang C.Y., Ho C.J., Hsieh I.C., Huang P.H., Huang A., Kuo J.Y., Lai W.T., Lee S.C., Lin T., Liu H.M., Tsai M.C., Tsao H.M., Tzong L., Ueng K.C., Wang Y.L., Wang H.C., Wang C.P., Yang C.C., Abaci F., Birdane A., Yilmaz M.B., Asim Oktay AO., Kan G., Koldas N., Ozcan I.T., Sahin M., Sahin T., Saka B., Tekten T., Ucar N., Uresin S., Yigit Z., Arif I., Bakhai A., Baksi A., Blagdon M., Brickman T., Brown N., Burton M., Burton J., Chaggar S., Chung A., Collier D., Covell W., Crawford G., Davies N., Davies M., Dayer M., Doughty A., Duff J., Dwenger E., Fisher J., Fitzpatrick L., Garner K., Glover J., Haughton G., Ilsley M., Ivan P., Voyzey E.J., Keenan S., Kelt T., Knight J., Kondagunta V., Lang C., Lee K., Lim L., Macdonald J., Mathew A., Mckenzie A., Mckibbin A., Michalska A., Pagett K., Pogson A., Price R., Price D., Procter K., Pye M., Redfearn H., Rewbury J., Ryding A., Sattar N., Sharp A., Shaw P., Simpson H., Smith W., Squire I., Storey R., Teenan M., Thomas H., Townend J., Trevelyan J., Wakeling J., Walukiewicz P., Wilkinson S., Zaman A., Acevedo L., Benton J., Abbate A., Aboufakher R., Acampora M., Acampora D., Aceto L., Acevedo B., Acheatel R., Adams M., Adams A., Ahmad I., Ahmed S.H., Aish B., Akyea-Djamson A., Al Joundi T., Alcide P., Alfieri A., Alfonso T., Alfrey A., Allen J., Alllison D.C., Almaliky T., Amos A., Angiolillo D., Antolick A., Ara M., Aragorn L., Arevalo S., Armas E., Arthur A., Asafu-Adjaye N., Ashcom T., Ashford M., Aslam A., Ather N., Atieh M., Aull L., Ayala M., Azizad M., Backer T., Baehl S., Bailey S., Bair S., Baker C., Ballmajo M., Pieretti H.B., Baquero A., Barnett S., Baron S., Bartkowiak A., Bashir K., Beall K., Beauregard L.A., Sarah S., Beckett L., Belejchak P., Bendelow T., Bender D., Benjamin S., Berdoff R., Berger V., Bergeron P., Berk M., Bernstein M., Binns Y., Bitzer V., Blahey M., Bloch S., Bluemel J., Boffetti P., Boley K., Bonner J., Boudreaux R., Boulanger K., Bradley A., Bramlet D., Bredlau C., Briggs S., Brousalis L., Brown S., Brown C., Buchannan C., Burke W., Burley T., Burton C., Burtt D., Byars W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge L., Fail P., Falcon D., Fang C., Fattal P., Fawson A., Felix L., Ferdinand K., Fien E., Fintel D., Firek C., Fitz-Patrick D., Flores E., Flores H., Floro T., Forker A., Foster M., Foucauld J., Lehman K.F., Fox B., Francoeur L., Frandsen B., Frivold G., Fruchter G., Fullerton D., Gabriel J., Gacioch G., Garas S., Garcia N., Garcia Rinaldi R., Garcia-Fragoso V., Garcia-Portela M., Gelb R., George F., Ghali J., Gilbert J., Gilley J., Glancy R., Goff R., Goldberg N., Gonzales D., Gonzales V., Gonzalez E., Gorges R., Gould R., Grabeau R., Grable M., Graham J.A., Graif J., Green E., Greener R., Greenway F., Grieshaber V., Griffin S., Gros C., Gudipati RVC., Guillinta P., Gupta V., Gutmann J., Gwyn M., El Hachem M., Hage F., Hageman T., Haidar A., Hakas J., Haldis T., Hall L., Hall C., Hall S., Halpern S., Hamud-Socoro A., Hardee L., Harrell W., Harrington A., Hartwell J., Hasan F., Hattler B., Haught H., Haynes E., Haywood A., Heaney L., Hecht J., Hernandez I., Herzog W., Hess E., Hill H., Hilton T., Hinderaker P., Hodnett P., Hoffman M., Hogan C., Holmes Z., Rees D.H., Hotchkiss D., Huang P., Humbert J., Hutchens E., Iachini K., Ibarra M., Igbokidi O., Ilahi T., Imbrognio M., Ipp E., Iteld B., Jacques G., Jafri A., Jafry B., Jardula M., Jefferson D., Jenkins R., Johnson E., Johnson J., Jones S., Kawahara M., Kelehan S., Kelly R., Kendall T., Kereiakes D., Khan M., Khan S., Kick J., Kimmel M., King T., King A., Kirkland S., Kissel S., Kitchens D., Klein P., Klugherz B., Korban E., Koren M., Korte M., Kostis J., Kotek L., Kozak M., Kreutter F., Kusnick B., Labovitz R., Lail J., Lamance J., Lamas G., Lambert J., Lambert C., Landzberg J., Langdon J., Lavoie W., Ledger G., Lee T., Lehman R., Leimbach W., Lennard M., Lepor N., Lester F., Levin P., Levinson L., Lewis D., Lillo J., Link L., Long C., Longaker R., Lorch G., Lucksinger G., Lynd S., Rhudy J.M., Madder R., Magness K., Maheshwari A., Alan A., Malek M., Maletz L., Malhotra V., Malhotra S., Mandviwala M., Mani C.K., Manuel J., Marchelletta N., Marshall L., Marsters M., Martin L., Martinez E., Mavromatis K., Maynard R., Mays M., Mays B., Mbulaiteye A., Mcalister R., Mccoy C., Mccrary D.Jr., Mccullough-O'Brien H., Mcdonald M., Mcgill J., Mcgrew F., Mckenzie C., Mclaurin B., Mclellan B.A., Mcneil D., Mcneill R., Mehrle A., Melbie K., Melliza T., Messina T., Meyer R., Michel K., Mikdadi G., Miller C., Miller R., Miller A., Miller G., Miller W., Mitchell J., Moats DJR., Mody F., Moffat J., Molk B., Molter D., Monroe T., Montero H., Montgomery R., Mookherjee D., Moran J., Moriarty P., Morrison J., Morton D., Moshayedi P., Mosley J., Moustafa M., Munshi K., Murray A., Mustafa J., Nadar V., Naidu R., Nalley J., Navy S., Neil L., Neutel J.M., Niblack P., Nicely V., Nicolai M., Nijmeh G., Nikas A., Nikyar A., Nixon S., Norman L., Noto G., Nour K., Nugent A., Ocman B., Odegard A., Olsen S., Ortiz-Carrasquillo R., Ossino N., Paez H., Palchick B., Paliwal Y., Pannell R., Parfait V., Partridge J., Patel B., Patel M., Patel S., Paysor C., Pena A., Pereira S., Perez M., Perez A., Perkins H., Perry B., Peters P., Phillippi C., Phillips A., Piacente R., Pintado M., Pish R., Pitt W., Poling T., Pomposini D., Poock J., Potts J., Poudrier R., Prior J., Pritchard C., Purighalla R., Quddusi K., Quinones J., Quinton D., Radin M., Radojcsics B., Rajput B., Rama B., Ramos M., Rauch R., Raynes K., Reber A.M., Reddy J., Reeves M., Reilly K., Renaud K., Resnick H., Reyes R., Richardson M., Riethof M., Riser J., Rodero M., Rodriguez Araya E., Roper L., Rozeman P., Ruder D., Runquist L., Sack G., Saint-Jacques H., Salfity M., Sall N., Sam K., Samal A., Sanchez D., Santiago J.Jr., Savignano C., Saylor R., Scheffel M., Schifferdecker B., Schindler E., Schneider P., Schneider R., Schnitzler R., Schrager B., Schwartz A., Scott R., Seals A., Shah A.V., Shah A., Shatsky K., Shayani S., Shealy N., Sheets L., Shelley J., Shepard P., Shetty S., Silver K., Simon M., Singh K., Singh N., Sizemore B.C., Skatrud L., Slayton C., Slimak V., Sloane G., Smallwood B., Smith P., Smith M., Smith T., Smith G., Smith B., Smith J., Soca Y., Sofley C., Sopko K., Sosa-Padilla M., Sotolongo R., Sprinkle B., Srivastava S., Starzec M., Steinhoff J., Stelly L., Stinson J., Stoddard M., Stoltz S., Stone B., Stover T., Strain J., Strugatsky S., Stys T., Suleman A., Sullivan P., Tamez W., Tandon N., Teltser M., Terry P.S., Terry K., Tessmar C., Thekkoott D., Thomas D., Thomas D.M., Thompson E., Thompson J., Thornton A., Tjaden T., Tobias C., Topper J., Tran A., Treasure C., Trenkamp P., Trevino M., Tsou L., Tuholske C., Uy W., Vahtel M., Vaid B., Valenzuela M., Vance A., Vandam J., Vanhecke T., Vanness WC III., Vargas R., Vaz S., Vazquez Tanus J., Veerina K., Vega J., Vento A., Vijay N., Voelker F., Vogt E., Vold D., Vora K., Wade R.D., Wadell C., Waksman R., Walker K., Wallace K., Warren M., Washam M., Watson B., Webel R., Wells T., West M., Whitaker J., White J., White C., White A., Wilhoit G., Wilkins M., Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., Zineldine A., Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., Kultursay H., Bilazarian S., East C., Forgosh L., Harris B., Ligueros M., Bohula E., Charmarthi B., Cheng S., Chou S., Danik J., McMahon G., Maron B., Ning M., Olenchock B., Pande R., Perlstein T., Pradhan A., Rost N., Singhal A., Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., Cosgrove S., Levine D., Lopes R., Scott J., Hilkert R., Tamesby G., Mickel C., Manning B., Woelcke J., Tan M., Manfreda S., Ponce T., Kam J., Saini R., Banker K., Salko T., Nandy P., Tawfik R., O’Neil G., Manne S., Jirvankar P., Lal S., Nema D., Jose J., Collins R., Bailey K., Blumenthal R., Colhoun H., Gersh B., Abreu M., Actis M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., 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Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., Sanchez Vallejo G., Luz Serrano H., Sotomayor A., Urina M., Vesga B., Yupanqui H., Akrap B., Busic N., Ciglenecki N., Cmrecnjak J., Fucak E., Gabor M., Jeric M., Jutrisa N., Kordic K., Planinc I., Popovic Z., Radeljic V., Sesto I., Sutalo K., Tusek S., Belohlavek J., Budkova J., Busak L., Capova L., Cech V., Cermak O., Coufalova Z., Cyprian R., Dedek V., Dedkova S., Ferkl R., Hanak P., Hanustiakova A., Homza M., Horackova K., Houra M., Iveta H., Kaiserova L., Kala P., Karel I., Kellnerova I., Koleckar P., Kreckova M., Krupicka J., Lorenc Z., Machova V., Malik J., Masarikova L., Matyasek I., Mikus M., Mikusova T., Ondrasik J., Otava M., Palubova L., Pavlickova L., Peterka M., Petrova I., Pokorna B., Povolny P., Radvan M., Reznakova S., Rickova Z., Roszkowska P., Rotreklova M., Samkova D., Skalicka H., Slechticka A., Sternthal P., Telekes P., Tesak M., Vesely P., Vesely J., Vins P., Vitovec M., Vodnansky P., Zidova M., Keba E., Laane E., Pool T., Randvee L., Ratnik E., Reimand M., Reinmets S., Rivis L., Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., Naumann R., Nebel J., Neumann J., Nuding S., Overhoff U., Papke B., Pencz I., Peter Y., Peukert A.M., Radde I., Rau T., Regner S., Reichenbach D., Reimer D., Rinke A., Roettges R., Romanski A., Rummel R., Samer H., Sanuri M., Sarnighausen H.E., Schäfer B., Scheibner T., Schermaul K.H., Schindler A., Schlundt C., Schmidt E., Schmidt K., Schnabel A., Schoen N., Schorn K., Schroeder T., Schulenburg D., Schulz M., Schulze U., Schulze J., Schumacher M., Schwerin G., Schwerin M., Stadelmeier S., Stahl H.D., Stahl A., Stockhausen J., Stockhausen G., Stoessel J., Stolze K., Stratmann M., Szymanowski N., Teschner A.B., Teske A., Uecker C., Veit S., Voeller H., Walter I., Walter J., Walther I., Weber H.G., Weimer J., Wichterich K., Wiebusch A., Willmerdinger M., Willner C., Winkelmann B., Winkler J., Wistuba T., Woehrle J., Wohnlich T., Wolf S., Woyczak D., Wrage P., Zirlik A., Anadiotis A., Chachalis 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Raghu C., Chauhan D., Chauhan H., Chavada J., Chaware G., Chella S., Chintala P., Dash D., Desai D., Devasia T., Dhanak R., Dobariya H., Dudhatra N., Duhan S., Fulwani M., Ghondale N., Ghosh S., Gohel P., Govindaraj D., Goyal B., Goyal S., Gundala A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., Makhe B., Mandati M., Mehta A., Minocha G., Mittal A., Modi R., Mohan K., Oomman A., Pai R., Pai V., Palaniswami N., Pansheriya A., Parekh N., Patel J., Patel R., Patole T., Praveen M., Radhakrishnan V., Rajan B A., Rajasekhar D., Rao M., Rao M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta 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T., Inagaki M., Ito K., Kaigawa K., Kajihara S., Kamiya H., Kamiya J., Kaneno Y., Katahira K., Kataoka M., Kawai M., Kawasaki T., Kojima E., Komura Y., Kuramochi T., Kuruma T., Kyo E., Mani H., Miyamoto T., Morii I., Morinaga Y., Morisawa T., Nagai Y., Naka T., Nakamura Y., Nakamura S., Nakayoshi K., Nishibe A., Ogawa M., Okada Y., Okawa M., Sakamoto Y., Sakurada M., Sasaki S., Seki S., Shimomura H., Shinozaki T., Sugimoto N., Suzuki A., Taguchi S., Takahashi J., Takase S., Tanabe K., Tanaka A., Tani S., Tomioka J., Tsuboi H., Tsuji M., Tsujita K., Tsujiyama S., Umesu A., Yamada T., Yamaguchi E., Yamamoto H., Yamamoto T., Yamane M., Yanase T., Yasuoka S., Yasutake M., Yokoyama M., Yoshida M., Yoshimoto E., Yunoki C., Balode A., Dormidontova G., Flaksa I., Nagele-Luse I., Rancane G., Sime I., Bartuseviciene S., Cepinskiene L., Dobilas V., Grigaraviciene I., Marcinkeviciene J., Mazutavicius R., Miliuniene R., Motiejuniene R., Norkiene S., Norkute-Macijauske U., Rudys A., Slapikas R., Stonkute K., Strazdiene D., Tijuneliene E., Urbonas G., Vanagiene S., Viezelis M., Arenas Leon JL., Bayram E., Carrillo J., Davalos C., De Los Rios M., Delgadillo T., Hernández N., Leon S., Mendoza N., Muñoz W., Ramos G., Anneveldt A., Bakker H., Brouwer M., Bunschoten P., De Boer P., De Jong C., De Vos A., Den Hartog F., Doesborg L., Dommerholt R., Drost I., Ellenbroek D., Engelen W., Folkeringa R.J., Hamer BJB., Herrman J.P., Hoogslag PAM., Jansen M., Jerzewski A., Joosten C., Kalkman C., Kietselaer B., Kok M., Kooiman E., Kose V., Lardinois R., Lenderink T., Lok DJA., Lousberg A., Meijlis P., Mulder R., Singerling M., Smeele F., Stroes E., Swart H.P., Ten Holt W., Van Der Wal M., Van Der Zwaan C., Van Kempen W.W., Van Maarseveen M., Van Stein I., Viergever E.P., Visseren FLJ., Voors C., Nugteren SKZ., Ata B., Berulfsen A., Rønnevik T.D., Dickstein K., Furuseth B., Grundtvig M., Hansen H., Hofsoey K., Høivik H.O., Bøen R.H., Hurtig U., Pettersen K.I., Johansen E., Kleve R., Kolleroy 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S., Brown C., Buchannan C., Burke W., Burley T., Burton C., Burtt D., Byars W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge 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Manuel J., Marchelletta N., Marshall L., Marsters M., Martin L., Martinez E., Mavromatis K., Maynard R., Mays M., Mays B., Mbulaiteye A., Mcalister R., Mccoy C., Mccrary D.Jr., Mccullough-O'Brien H., Mcdonald M., Mcgill J., Mcgrew F., Mckenzie C., Mclaurin B., Mclellan B.A., Mcneil D., Mcneill R., Mehrle A., Melbie K., Melliza T., Messina T., Meyer R., Michel K., Mikdadi G., Miller C., Miller R., Miller A., Miller G., Miller W., Mitchell J., Moats DJR., Mody F., Moffat J., Molk B., Molter D., Monroe T., Montero H., Montgomery R., Mookherjee D., Moran J., Moriarty P., Morrison J., Morton D., Moshayedi P., Mosley J., Moustafa M., Munshi K., Murray A., Mustafa J., Nadar V., Naidu R., Nalley J., Navy S., Neil L., Neutel J.M., Niblack P., Nicely V., Nicolai M., Nijmeh G., Nikas A., Nikyar A., Nixon S., Norman L., Noto G., Nour K., Nugent A., Ocman B., Odegard A., Olsen S., Ortiz-Carrasquillo R., Ossino N., Paez H., Palchick B., Paliwal Y., Pannell R., Parfait V., Partridge J., Patel B., 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Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., and Zineldine A.

Abstract

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83

34. Exploring hypertension-linked diseases: a comprehensive review of innovative drug combinations with enhanced therapeutic potential.

Author

Thakkar B, Dadhaniya H, and Dudhat K

Abstract

Hypertension, a prevalent cardiovascular condition affecting a substantial portion of the global population, remains a formidable health challenge associated with a multitude of complications. This review article provides a comprehensive examination of hypertension, its various complications, and the emergence of a novel management technique that shows promising potential in transforming the therapeutic landscape. Over the years, conventional treatment approaches, encompassing lifestyle modifications, dietary interventions, and pharmacotherapy, have been the mainstay in managing hypertension. However, these strategies fall short in achieving optimal blood pressure control and preventing complications in a significant number of patients. Consequently, the medical community has ventured into exploring innovative management techniques to tackle this unmet medical need. The focal point of this review centers on the emergence of a new management technique for hypertension that exhibits promise in preclinical and clinical studies. The latest research findings shed light on the efficacy and safety of this innovative approach, which encompasses pharmaceutical agents, medical devices, and non-invasive interventions. Through critical analysis and discussion, we explore the potential impact of these novel strategies on hypertension management and patient outcomes. In conclusion, this review article provides a comprehensive overview of hypertension, its complications, and the promising emergence of innovative management techniques. By acknowledging the complexity of hypertension and the potential of new therapeutic avenues, we aspire to pave the way for improved patient care, enhanced quality of life, and ultimately, the mitigation of hypertension-related morbidity and mortality., Competing Interests: Declarations. Consent for publication: Not applicable. Ethical declaration: This publication was created based on a formal academic evaluation and information about potential treatments; no human or animal subjects were used, and there was no investigational review board involvement. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2025
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35. Beyond the Norm: Acute Multifocal Diverticulitis.

Author

Thakkar B, Tidwell J, Nguyen MTT, Yu G, and Parikh N

Abstract

Colonic diverticulitis is inflammation of diverticula, which are sac-like protrusions in the colonic wall. It is thought that increased intraluminal pressure and trapped food leads to inflammation. Newer theories suggest that alterations in the gut microbiome and chronic inflammation play a role as well. Diverticulitis commonly affects discrete sections of colon. Acute multifocal diverticulitis is defined as diverticulitis in at least 2 different sites of the colon separated by at least 10 cm, which is very rare. Ideal management is unclear; however, our patient improved with supportive measures and antibiotics without complications of abscess, perforation, or need for surgery., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Published
2024
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36. The impact of adverse childhood experiences on multimorbidity: a systematic review and meta-analysis.

Author

Senaratne DNS, Thakkar B, Smith BH, Hales TG, Marryat L, and Colvin LA

Subjects
Humans, Child, Prevalence, Adult, Adolescent, Adverse Childhood Experiences statistics & numerical data, Multimorbidity
Abstract

Background: Adverse childhood experiences (ACEs) have been implicated in the aetiology of a range of health outcomes, including multimorbidity. In this systematic review and meta-analysis, we aimed to identify, synthesise, and quantify the current evidence linking ACEs and multimorbidity., Methods: We searched seven databases from inception to 20 July 2023: APA PsycNET, CINAHL Plus, Cochrane CENTRAL, Embase, MEDLINE, Scopus, and Web of Science. We selected studies investigating adverse events occurring during childhood (< 18 years) and an assessment of multimorbidity in adulthood (≥ 18 years). Studies that only assessed adverse events in adulthood or health outcomes in children were excluded. Risk of bias was assessed using the ROBINS-E tool. Meta-analysis of prevalence and dose-response meta-analysis methods were used for quantitative data synthesis. This review was pre-registered with PROSPERO (CRD42023389528)., Results: From 15,586 records, 25 studies were eligible for inclusion (total participants = 372,162). The prevalence of exposure to ≥ 1 ACEs was 48.1% (95% CI 33.4 to 63.1%). The prevalence of multimorbidity was 34.5% (95% CI 23.4 to 47.5%). Eight studies provided sufficient data for dose-response meta-analysis (total participants = 197,981). There was a significant dose-dependent relationship between ACE exposure and multimorbidity (p < 0.001), with every additional ACE exposure contributing to a 12.9% (95% CI 7.9 to 17.9%) increase in the odds for multimorbidity. However, there was heterogeneity among the included studies (I 2  = 76.9%, Cochran Q = 102, p < 0.001)., Conclusions: This is the first systematic review and meta-analysis to synthesise the literature on ACEs and multimorbidity, showing a dose-dependent relationship across a large number of participants. It consolidates and enhances an extensive body of literature that shows an association between ACEs and individual long-term health conditions, risky health behaviours, and other poor health outcomes., (© 2024. Crown.)

Published
2024
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37. Primary Hepatic Neuroendocrine Carcinoma: A Rare Entity.

Author

Tidwell J, Thakkar B, Nguyen MTT, Parker S, and Schoenfeld A

Abstract

Neuroendocrine tumors are typically low-malignancy growths arising from neuroectodermal cells of neural crest origin. Neuroendocrine carcinoma, on the other hand, represents a high-malignancy form of these tumors. While rare in the liver, they often indicate metastasis when present. We present a unique case of incidentally discovered primary hepatic neuroendocrine carcinoma. Initially, the patient's management was based on misleading radiological findings. However, histopathology confirmed the diagnosis, with subsequent imaging ruling out an extrahepatic source. Despite this, the patient opted against surgical intervention, resulting in a fatal outcome. This case underscores the critical importance of prompt diagnosis and intervention to avert adverse outcomes., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Published
2024
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38. Etiologies of Splenic Venous Hypertension: A Review.

Author

Tidwell J, Thakkar B, and Wu GY

Abstract

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development., Competing Interests: GYW has been an Editor-in-Chief of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflicts of interest related to this publication., (© 2024 Authors.)

Published
2024
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39. Single Session Effects of Prolonged Continuous Theta Burst Stimulation Targeting Two Brain Regions on Pain Perception in Patients with Painful Diabetic Neuropathy: A Preliminary Study.

Author

Thakkar B, Peterson CL, and Acevedo EO

Subjects
Humans, Transcranial Magnetic Stimulation methods, Single-Blind Method, Prospective Studies, Pain Perception, Brain, Prefrontal Cortex physiology, Treatment Outcome, Chronic Pain etiology, Diabetic Neuropathies therapy, Neuralgia etiology, Diabetes Mellitus etiology
Abstract

Background: Painful diabetic neuropathy (pDN) is the most common cause of neuropathic pain (NP) in the United States. Prolonged continuous theta burst stimulation (pcTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is quick (1-4 minutes) and tolerable for most individuals, compared to high frequency rTMS and can modulate pain thresholds in healthy participants. However, its effects on patients with chronic pain are still unclear. The primary purpose of this preliminary study is to investigate the effects of single session pcTBS targeted at the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) on a set of self-report measures of pain (SRMP) that assess the (a) sensory-discriminative; (b) affective-motivational; and (c) cognitive-evaluative aspects of pain experience., Methods: For this prospective, single-blind study, forty-two participants with pDN were randomized to receive either pcTBS targeting the M1 or the DLPFC brain regions. SRMP were completed at baseline, post pcTBS and 24h-post pcTBS. A two-way mixed model repeated measures analysis of variance (2 brain regions by 3 time points) was conducted to evaluate the effects of pcTBS stimulation at M1 and DLPFC for each subscale of each SRMP., Results: After a single session of pcTBS targeted at M1 or DLPFC in patients with pDN, statistically significant improvements from baseline to post pcTBS and baseline to 24 h-post pcTBS were observed for different SRMP subscales examining the (a) sensory-discriminative, (b) affective-motivational and (c) cognitive-evaluative components of the pain experience. At 24 h-post pcTBS, none of the participants reported any serious adverse events to the pcTBS treatment, thus demonstrating its feasibility., Conclusions: In pDN patients with NP, our study results demonstrated significant improvement in scores on self-report measures of pain (SRMP) after a single session of pcTBS targeting the M1 and DLPFC brain regions. Future studies should consider utilizing multiple sessions of pcTBS to evaluate its long-term effects on pain perception, safety and tolerability in patients with chronic pain., Clinical Trial Registration: This study was registered on the ClinicalTrials.gov website (NCT04988321)., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Published
2024
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40. Expanding Medical Education to Include Substance Use Disorders During Pregnancy and Postpartum: Preliminary Effectiveness of a Pilot Curriculum for Medical Students.

Author

Martin CE, Martinez Telleria M, Hostetter K, Thumma L, Edwards C, and Thakkar B

Subjects
Pregnancy, Humans, Female, Curriculum, Postpartum Period, Students, Medical, Internship and Residency, Substance-Related Disorders therapy
Abstract

Objective: To effectively combat the simultaneous overdose and maternal mortality crises, a multimodal approach is needed. The aim of this study is to evaluate the preliminary effectiveness of a pilot, experiential learning, substance use disorder (SUD) curriculum embedded into a third-year medical student obstetrics and gynecology clerkship to improve self-reported confidence in SUD clinical skills., Methods: This SUD curriculum was designed and implemented in an outpatient clinic, which provides integrated obstetric, gynecologic, and addiction medicine services for pregnant and parenting people with SUD. Third-year medical students on their obstetrics and gynecology clerkship rotated 1 full day through the OB MOTIVATE clinic between August 2020 and April 2022 and completed this curriculum. Students completed preclinic assignments and in-clinic tasks (eg, practicing SBIRT under supervision: screening, brief intervention, referral to treatment). Paired t tests assessed changes in outcomes, with increasing scores (range 1-5) demonstrating improvement., Results: Sixty-three students rotated through the OB MOTIVATE clinic; 57 completed the curriculum and surveys. Results from the self-assessment tools demonstrated significant improvements in confidence in SUD clinical skills, including performing SBIRT (2.46 ± 0.80 vs 4.07 ± 0.59, P < 0.01), motivational interviewing (2.98 ± 0.86 vs 4.16 ± 0.65, P < 0.01), using evidence-based medicine (2.91 ± 1.09 vs 4.23 ± 0.66, P < 0.01), and collecting an SUD history (3.25 ± 1.04 vs 4.35 ± 0.55, P = 0.01)., Conclusions: The integration of interventional curriculums into medical school and residency programs could be an effective avenue to reinforce addiction knowledge and teach new skills. This practical 1-day pilot curriculum demonstrated preliminary effectiveness at introducing third-year medical students to the complexities of SUD in pregnancy and postpartum. Further investigations of feasible and acceptable SUD educational interventions are warranted., Competing Interests: The other authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Published
2024
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41. A Novel Home for Hemangiomas: Sclerosing Hemangioma in the Pancreas.

Author

Tidwell J, Thakkar B, Nguyen MTT, Zakko L, Potashinsky A, and Parker S

Abstract

Pancreatic hemangiomas, predominantly in female patients, are rare benign vascular tumors. We report a unique case of an incidentally discovered pancreatic sclerosing hemangioma. The patient's clinical presentation and imaging were concerning for an abdominal mass. Endoscopic ultrasound and histopathology confirmed the pancreatic sclerosing hemangioma. Because there were no complications, surgery was not performed, and the patient was monitored. Biopsy confirmation is crucial to rule out malignancy and avoid unnecessary surgical resection., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Published
2024
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42. Prolonged continuous theta burst stimulation increases motor corticospinal excitability and intracortical inhibition in patients with neuropathic pain: An exploratory, single-blinded, randomized controlled trial.

Author

Thakkar B, Peterson CL, and Acevedo EO

Subjects
Aged, Female, Humans, Male, Middle Aged, Diabetes Mellitus, Type 2 physiopathology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 therapy, Diabetic Neuropathies physiopathology, Diabetic Neuropathies therapy, Neural Inhibition physiology, Single-Blind Method, Theta Rhythm physiology, Evoked Potentials, Motor physiology, Motor Cortex physiopathology, Neuralgia physiopathology, Neuralgia therapy, Pyramidal Tracts physiopathology, Transcranial Magnetic Stimulation methods
Abstract

Objectives: A new paradigm for Transcranial Magnetic Stimulation (TMS), referred to as prolonged continuous theta burst stimulation (pcTBS), has recently received attention in the literature because of its advantages over high frequency repetitive TMS (HF-rTMS). Clinical advantages include less time per intervention session and the effects appear to be more robust and reproducible than HF-rTMS to modulate cortical excitability. HF-rTMS targeted at the primary motor cortex (M1) has demonstrated analgesic effects in patients with neuropathic pain but their mechanisms of action are unclear and pcTBS has been studied in healthy subjects only. This study examined the neural mechanisms that have been proposed to play a role in explaining the effects of pcTBS targeted at the M1 and DLPFC brain regions in neuropathic pain (NP) patients with Type 2 diabetes., Methods: Forty-two patients with painful diabetic neuropathy were randomized to receive a single session of pcTBS targeted at the left M1 or left DLPFC. pcTBS stimulation consisted of 1,200 pulses delivered in 1 min and 44 s with a 35-45 min gap between sham and active pcTBS stimulation. Both the activity of the descending pain system which was examined using conditioned pain modulation and the activity of the ascending pain system which was assessed using temporal summation of pain were recorded using a handheld pressure algometer by measuring pressure pain thresholds. The amplitude of the motor evoked potential (MEP) was used to measure motor corticospinal excitability and GABA activity was assessed using short (SICI) and long intracortical inhibition (LICI). All these measurements were performed at baseline and post-pcTBS stimulation., Results: Following a single session of pcTBS targeted at M1 and DLPFC, there was no change in BPI-DN scores and on the activity of the descending (measured using conditioned pain modulation) and ascending pain systems (measured using temporal summation of pain) compared to baseline but there was a significant improvement of >13% in perception of acute pain intensity, increased motor corticospinal excitability (measured using MEP amplitude) and intracortical inhibition (measured using SICI and LICI)., Conclusion: In patients with NP, a single session of pcTBS targeted at the M1 and DLPFC modulated the neurophysiological mechanisms related to motor corticospinal excitability and neurochemical mechanisms linked to GABA activity, but it did not modulate the activity of the ascending and descending endogenous modulatory systems. In addition, although BPI-DN scores did not change, there was a 13% improvement in self-reported perception of acute pain intensity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Published
2023
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43. Extracolonic manifestations of Gardner syndrome: A case report.

Author

Blackwell MC, Thakkar B, Flores A, and Zhang W

Abstract

Gardner syndrome has head and neck manifestations that may be recognized during dental visits. Features such as multiple gnathic osteomas, impacted supernumerary teeth, and multiple foci of idiopathic osteosclerosis can be easily identified on dental radiographs, prompting the clinician to refer the patient for further investigation. A dental examination and routine radiographs play a vital role in revealing the extracolonic presentation of Gardner syndrome, which facilitates timely screening and detection of colorectal cancer and other malignancies associated with this condition. This report discusses the case of a 50-year-old Caucasian man who presented with a hard swelling of the left angle of the mandible and was diagnosed with Gardner syndrome based on abnormal findings from an oral examination, dental imaging, and medical and family history., Competing Interests: Conflicts of Interest: None, (Copyright © 2023 by Korean Academy of Oral and Maxillofacial Radiology.)

Published
2023
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44. Incidence Rates and Clinical Characteristics of Patients With Confirmed Myocarditis or Pericarditis Following COVID-19 mRNA Vaccination: Experience of the Veterans Health Administration Through 9 October 2022.

Author

Luo J, Hur K, Salone C, Huang N, Burk M, Pandey L, Thakkar B, Donahue M, and Cunningham F

Abstract

Background: Although the benefits outweigh the risks, COVID-19 vaccines have been associated with an increased risk of myocarditis and pericarditis. This report is based on a national US veteran population with confirmed myocarditis/pericarditis following mRNA COVID-19 vaccines according to the near real-time active surveillance program of Veterans Affairs., Methods: This study is based on a cohort evaluation of all adults administered ≥1 mRNA COVID-19 vaccine, including boosters, in the Veterans Health Administration between 14 December 2020 and 9 October 2022. ICD-10-CM diagnosis codes were used to identify potential safety signals in near real time through a database analysis. All potential cases of myocarditis/pericarditis identified in the database analysis underwent in-depth chart review and case validation by a team of pharmacists and expert clinicians. Our main outcome was the incidence rate of confirmed myocarditis/pericarditis among vaccine recipients (overall and those aged 18-39 years) within 21 days of a first, second, or booster dose of a mRNA COVID-19 vaccine. We calculated the ratio of observed events among COVID-19 vaccine recipients over expected events from historical vaccine recipient controls (2015-2020) in the Veterans Health Administration. We used confirmed cases to calculate incidence rates and 95% CIs., Results: Through 9 October 2022, 3 877 453 doses of BNT162b2 (Pfizer-BioNTech) and 4 221 397 doses of mRNA-1273 (Moderna) were administered as first or second dose across Veterans Affairs, and 1 012 561 BNT162b2 and 1 156 160 mRNA-1273 booster doses were administered. Among all doses, the rapid cycle analysis identified 178 potential cases of myocarditis/pericarditis among vaccinees of any age and 22 potential cases among those aged 18-39 years. Of these, 33 cases, including 6 among those 18-39 years old, were confirmed after in-depth chart review and validation, corresponding with an overall incidence rate per million ranging from 0.46 (95% CI, .01-2.55) for Moderna dose 1 to 6.91 (95% CI, 2.78-14.24) for Pfizer booster. Among those aged 18-39, incidence rates ranged from 7.1 (95% CI, .18-39.56) for Moderna dose 2 to 19.76 (95% CI, 5.38-50.58) for Pfizer dose 2. Patients with confirmed cases were hospitalized for a mean 4.1 days (range, 1-15). The final disposition for 32 (97%) of 33 cases was discharge to home., Conclusions: This report is a real-world demonstration of the Veterans Affairs' active surveillance system for vaccines. Although the rapid cycle analysis initially identified 178 potential cases of myocarditis/pericarditis, only 1 of 5 cases was confirmed to be related to a COVID-19 vaccine after chart review. These findings highlight the paramount importance of active surveillance and chart validation for rare but serious adverse events related to COVID-19 vaccines., Competing Interests: Potential conflicts of interest. K. H., C. S., N. H., M. B., F. C., B. T., and L. P. are employees of VA Center for Medication Safety. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Published
2023
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45. Assessment of COVID-19-Driven Changes in an Integrated OBGYN-Addiction Treatment Clinic and Future Implications.

Author

Smarony S, Parlier-Ahmad AB, Shadowen H, Thakkar B, Scheikl MO, and Martin CE

Subjects
Female, Pregnancy, Humans, COVID-19 Vaccines, Pandemics, Ambulatory Care, COVID-19, Buprenorphine therapeutic use, Telemedicine
Abstract

Objective: The COVID-19 pandemic prompted healthcare delivery changes, but the associated impacts on substance use disorder treatment outcomes among pregnant and parenting people are unknown. This study aims to (1) describe COVID-19-driven clinical practice changes, (2) evaluate clinic-level visit attendance patterns, and (3) compare patient-level treatment engagement outcomes across 3 COVID-19 pandemic phases in an OBGYN-addiction treatment clinic., Methods: COVID-19 phases include pre-COVID-19 (August 2019-February 2020), early COVID-19 (March-December 2020), and COVID-19 vaccine (January-July 2021). OBGYN-addiction treatment clinical practice changes were summarized. Clinic-level attended medical provider visits were analyzed. Patient-level treatment engagement outcomes (buprenorphine continuation, visit attendance, and virtual visits) were assessed in a cohort of pregnant and parenting people enrolled in a clinic research registry. Mixed-level logistic regression models determined the relationship between the COVID-19 phases and the patient-level outcomes., Results: The study site made several COVID-19-driven clinical practice changes, including implementing a hybrid virtual/in-person system for medical visits. Clinic-level medical provider appointments increased between the first and second COVID-19 phases and remained high in the third phase. Among participants included in patient-level outcome analyses (N = 27), there were no differences in the early COVID-19 phase compared with the pre-COVID-19 phase in buprenorphine continuation, any visits, or medical visits. There was a decrease in all patient-level outcomes in the COVID-19 vaccine phase compared with pre-COVID-19 ( P < 0.05). Virtual visits increased between the first 2 phases and remained high during the third., Conclusion: Within our OBGYN-addiction treatment clinic, implementation of tailored, patient-centered treatment strategies supported clinic- and patient-level treatment engagement throughout the pandemic., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Published
2023
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46. Incarceration status at buprenorphine initiation and OUD treatment outcomes during pregnancy.

Author

Nguyen A, Shadowen H, Shadowen C, Thakkar B, Knittel AK, and Martin CE

Abstract

Introduction: Opioid use disorder (OUD) is a leading cause of pregnancy-associated deaths. OUD treatment with buprenorphine (BUP) reduces overdose risk and improves perinatal outcomes. Incarceration can be a barrier to receipt of OUD treatment during pregnancy and postpartum. The objective of this study was to examine differences in BUP continuation at delivery by patients' incarceration status at the time of BUP initiation., Methods: This is a secondary analysis of a retrospective cohort study of pregnant patients with OUD who delivered at an academic medical center and initiated BUP between January 1, 2018, and March 30, 2020. The primary outcome was BUP continuation at delivery, abstracted from the state prescription monitoring program and electronic medical record, along with incarceration status. Bivariate analysis was used to assess the relationship between BUP continuation and incarceration status., Results: Our sample included 76 patients, with 62% of patients incarcerated at BUP initiation ( n = 47). Among the entire sample, 90.7% ( n = 68) received BUP at delivery. Among patients who were incarcerated at BUP initiation, 97% remained on BUP at delivery; among patients who were not incarcerated at BUP initiation, 79% remained on BUP at delivery ( p = 0.02)., Conclusion: In our sample from a health system housing a care model for pregnant and parenting people with OUD with local jail outreach, BUP continuation rates at delivery were high, both for patients who were and were not incarcerated at BUP initiation. Findings are intended to inform future work to develop and evaluate evidence-based, patient-centered interventions to expand OUD treatment access for incarcerated communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Shadowen, Shadowen, Thakkar, Knittel and Martin.)

Published
2023
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47. Harm Reduction Approach to Increasing Self-reported Safe Medication Storage Among Pregnant and Parenting People Receiving Opioid Use Disorder Treatment.

Author

Grist E, Thakkar B, Dacha P, Lutins E, Maxwell M, and Martin CE

Subjects
Pregnancy, Female, Humans, Self Report, Harm Reduction, Parenting, Buprenorphine, Naloxone Drug Combination therapeutic use, Narcotic Antagonists therapeutic use, Opioid-Related Disorders drug therapy, Buprenorphine therapeutic use
Abstract

Objectives: The expansion of access to buprenorphine-naloxone (BUP-NAL) for the treatment of opioid use disorder (OUD) is critical to combat the overdose crisis. Evidence is lacking to guide providers on how to best promote BUP-NAL medication safety for their patients. This study assessed (1) the current medication storage practices among a sample of pregnant and parenting people receiving BUP-NAL for OUD; (2) the feasibility and acceptability of providing a lockbox for safe medication storage., Methods: Pregnant and/or parenting patients receiving sublingual BUP-NAL in an outpatient OUD clinic were recruited between June and November 2021. Participants completed a baseline survey, received a lockbox, and a follow-up survey 3 to 8 weeks later. The primary outcome of current self-reported safe medication storage practice was defined by storing BUP-NAL in a locked/latched place "almost always" or "always" on the baseline survey. Outcomes were analyzed using simple proportions., Results: Sixty-three participants completed the baseline survey, and 50 completed the follow-up survey. Baseline survey results indicated that only a quarter of patients (26.6%) were practicing safe BUP-NAL medication storage practices. At follow up, 93.6% of patients were using the lockbox provided by the study, 93.4% reported being satisfied with the lockbox, and most participants (89.3%) reported safe BUP-NAL medication storage practices., Conclusions: Many pregnant and parenting patients with OUD receiving BUP-NAL do not store their medications safely. The provision of a lockbox as part of OUD treatment is a feasible, acceptable, and potentially effective harm reduction intervention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Published
2023
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48. BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges.

Author

Thakkar B and Acevedo EO

Subjects
Animals, Humans, Brain-Derived Neurotrophic Factor, Biomarkers, Central Nervous System, Neuralgia diagnosis, Chronic Pain
Abstract

Introduction: The primary objective of this paper is to (1) provide a summary of human studies that have used brain derived neurotrophic factor (BDNF) as a biomarker, (2) review animal studies that help to elucidate the mechanistic involvement of BDNF in the development and maintenance of neuropathic pain (NP), and (3) provide a critique of the existing measurement techniques to highlight the limitations of the methods utilized to quantify BDNF in different biofluids in the blood (i.e., serum and plasma) with the intention of presenting a case for the most reliable and valid technique. Lastly, this review also explores potential moderators that can influence the measurement of BDNF and provides recommendations to standardize its quantification to reduce the inconsistencies across studies., Methods: In this manuscript we examined the literature on BDNF, focusing on its role as a biomarker, its mechanism of action in NP, and critically analyzed its measurement in serum and plasma to identify factors that contribute to the discrepancy in results between plasma and serum BDNF values., Results: A large heterogenous literature was reviewed that detailed BDNF's utility as a potential biomarker in healthy volunteers, patients with chronic pain, and patients with neuropsychiatric disorders but demonstrated inconsistent findings. The literature provides insight into the mechanism of action of BDNF at different levels of the central nervous system using animal studies. We identified multiple factors that influence the measurement of BDNF in serum and plasma and based on current evidence, we recommend assessing serum BDNF levels to quantify peripheral BDNF as they are more stable and sensitive to changes than plasma BDNF., Conclusion: Although mechanistic studies clearly explain the role of BDNF, results from human studies are inconsistent. More studies are needed to evaluate the methodological challenges in using serum BDNF as a biomarker in NP., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Published
2023
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49. Paired pulse transcranial magnetic stimulation in the assessment of biceps voluntary activation in individuals with tetraplegia.

Author

Roumengous T, Thakkar B, and Peterson CL

Abstract

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VA TMS ) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VA TMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VA TMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VA TMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VA TMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VA TMS . Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VA TMS . Future work is needed to address methodological issues that limit clinical application of VA TMS ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Roumengous, Thakkar and Peterson.)

Published
2022
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50. Effect of neuroanatomy on corticomotor excitability during and after transcranial magnetic stimulation and intermittent theta burst stimulation.

Author

Mittal N, Thakkar B, Hodges CB, Lewis C, Cho Y, Hadimani RL, and Peterson CL

Subjects
Evoked Potentials, Motor physiology, Humans, Neuroanatomy, Neuronal Plasticity physiology, Theta Rhythm physiology, Motor Cortex diagnostic imaging, Motor Cortex physiology, Transcranial Magnetic Stimulation
Abstract

Individual neuroanatomy can influence motor responses to transcranial magnetic stimulation (TMS) and corticomotor excitability after intermittent theta burst stimulation (iTBS). The purpose of this study was to examine the relationship between individual neuroanatomy and both TMS response measured using resting motor threshold (RMT) and iTBS measured using motor evoked potentials (MEPs) targeting the biceps brachii and first dorsal interosseus (FDI). Ten nonimpaired individuals completed sham-controlled iTBS sessions and underwent MRI, from which anatomically accurate head models were generated. Neuroanatomical parameters established through fiber tractography were fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD) at the point of stimulation. Cortical magnetic field induced electric field strength (EFS) was obtained using finite element simulations. A linear mixed effects model was used to assess effects of these parameters on RMT and iTBS (post-iTBS MEPs). FDI RMT was dependent on interactions between EFS and both FTSA and TFC. Biceps RMT was dependent on interactions between EFS and and both FTSA and BSD. There was no groupwide effect of iTBS on the FDI but individual changes in corticomotor excitability scaled with RMT, EFS, BSD, and FTSA. iTBS targeting the biceps was facilitatory, and dependent on FTSA and TFC. MRI-based measures of neuroanatomy highlight how individual anatomy affects motor system responses to different TMS paradigms and may be useful for selecting appropriate motor targets when designing TMS based therapies., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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