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9. Statistical properties of the estimated degree of polarization

Author

Medkour, T. and Walden, A.T.

Subjects
Confidence intervals -- Evaluation, Polarization (Electricity) -- Analysis, Solar magnetic field -- Analysis, Business, Computers, Electronics, Electronics and electrical industries
Abstract

Important and useful new statistical properties of the estimated degree of polarization in the two-dimensional case are derived. The statistical analyses enable identification of elliptical polarization for an ultra low frequency wave in the solar magnetic field.

Published
2008

11. Vorapaxar in the secondary prevention of atherothrombotic events

Author

Braunwald E, Morrow DA, Scirica BM, Bonaca MP, McCabe CH, Morin S, Fish P, Lamp J, Gershman E, Murphy S, Deenadayalu N, Skene A, Hill K, Bennett L, Strony J, Plat F, Berman G, Lipka L, Kilian A, He W, Liu X, Fox KA, Aylward P, Bassand JP, Betriu A, Bounameaux H, Corbalan R, Creager M, Dalby A, De Ferrari G, Dellborg M, Diehm CH, Dietz R, Goto S, Grande P, Gurbel P, Hankey G, Isaza D, Jensen P, Kiss R, Lewis B, Merlini P, Moliterno D, Morais J, Nicolau JC, Nieminen M, Nilsen D, Olin J, Ophuis TO, Paolasso E, Pichler M, Shinohara Y, Spinar J, Teal P, Tendera M, Theroux P, Thomassen L, Van de Werf F, White H, Wilcox R, Alberts M, Ameriso S, Diener H, Mohr J, Welch M, Wiviott SD, Awtry E, Berger C, Desai A, Gelfand E, Ho C, Leeman D, Link M, Norden A, Pande A, Rost N, Ruberg R, Silverman S, Singhal A, Vita J, Frye RL, Bailey KR, Easton J, Hochman J, Steg PG, Verheught F, Lee K, Mauro DO, Centurion A, Carlevaro O, Cardozo E, Cartasegna L, Soccini N, Farras HA, Molina Aguirre E, Duronto E, Arrechavala L, Rey R, Stilman A, Fernández H, Marinsalta G, Tartaglione J, Chekherdemian M, Povedano G, Casares E, Kantor P, Reges P, Cuneo C, Martinez G, MacKinnon I, Bagnato B, Fernandez A, Funosas C, Lozada A, Barilati P, Ferrari J, Ferrari N, Llanos J, Casaccia G, Giannaula R, García Méndez C, Cirio J, García Dávila C, Estol C, Chiezzo D, Ramirez J, Garrido S, López M, Hominal M, Bianchini MV, Ramos M, Verdini E, Herrera G, Monne H, Ioli P, Samudio MA, Rotta Escalante R, Tarulla A, Reich E, Perez G, Milesi R, Berli M, Marino J, Funes I, Prado A, Bezi M, Fernandez R, Rojas M, Cimbaro Canella JP, Galarza Salazan M, Chew D, Horsfall L, Claxton A, French J, O'Brien K, Nelson G, Loxton A, McCann A, Downey C, Aroney C, Cleave P, Worthley S, Roach A, Amerena J, Long A, Thompson P, Ferguson L, Fitzpatrick M, Mackenzie M, Youssef G, Goldsmith H, Jayasinghe R, Quinlan S, Arstall M, Rose J, Counsell J, Martin M, Crimmins D, Slattery A, Anderson C, Paraskevaidis T, Davis S, Silver G, Gerraty RP, Gapper J, Donnan G, Petrolo S, Whelan A, Tulloch G, Singh B, Campo Ma, Dick R, Savage C, Hill A, Conway B, Waites J, Keays P, Kopp K, Hainzer D, Podczeck Schweighofer A, Priesnitz T, Drexel H, Hagspiel V, Foeger B, Hilbe C, Trinka E, Sinadinoska D, Pilger E, Brodmann M, Stöllberger C, Jungbauer LV, Koppensteiner R, Hoke M, Grisold W, Berger O, Gaul GB, Fazekas N, Wandaller C, Stockenhuber F, Rek A, Willeit J, Zangerle A, Kiechl S, Sturm W, Theurl M, Gruber F, Schacherl S, Auer J, Primus C, Eber B, Ammer M, Hofer JF, Mayr H, Moser S, Hoellmueller I, Van der Werf F, Motte S, Jorion M, Schroë H, Zwinnen W, Vermassen F, Geenens M, De Wolf L, Briké C, De Deyn P, Ongena P, De Klippel N, Meeuwissen K, Desfontaines P, Tincani G, Vandermeeren Y, de Fays K, Pandolfo M, Alaerts N, Peeters A, Findik A, Tack P, deGrande E, Thijs V, Marcelis E, Van Landegem W, Vanhagendoren S, Vanhooren G, Schotte V, Celen H, Bes N, De Letter J, Holvoet G, Claerbout B, Verhamme P, Debaveye B, Bourgeois P, Debrabandere K, Stalpaert S, Dhondt E, De Maeseneire S, De Bleecker J, de Koning K, Vincent M, Tahon S, Monté C, Maes J, Vossaert R, Vandenhoven C, Roosen J, Vissers C, Sinnaeve P, de Velder L, Thoeng J, Cauwenberghs J, Deceuninck F, Nicolau J, Ardito WR, Queirantes C, de Araujo Filho JD, Queirantes CS, Ribeiro JP, Guizzardi SP, Chaves ML, Titton NF, Pereira AH, Webber I, da Silva DG Jr, Uehara RM, Brasileiro J, Maia LN, Souza A, Bodanese LC, Homem R, Friedrich MA, Macagnan AP, Dutra OP, Brum AB, Rossi PR, Herek L, Feitosa GS, Bernardes Ade S, Braga J, Rodrigues D, Guimarães A, Teixeira AB, Marin Neto JA, Tonani M, Piegas LS, Amato V, Leães P, Osorio RL, Ganem F, Vieira AP, Leao P, Kanashiro V, Franken RA, Martins EP, Gagliardi RJ, Silva L, Caffaro RA, Novaes GS, Carvalho A, Laet VL, Miranda F. Jr, Crippa BA, Saraiva JF, Ormundo CT, Speciali JG, Guandolini G, de Albuquerque DC, Silva V, Abrantes JA, Pinheiro L, Teixeira MS, Guanaes DF, Resende ES, Andrade SF, Alves ÁR Jr, Oliveira OM, Tauil CB, Araujo E, de Souza J, de Freitas GR, Horokosky AP, Barbosa EC, Muniz P, de Moraes JB Jr, Cabral M, Faria Neto JR, Belemer A, Paiva MS, Brito A, Hernandes ME, Amorim R, Pittella FJ, Brito HH, Kouz S, Roy M, Gosselin G, David M, Huynh T, Boudreault C, Heath J, Scott L, Bhargava R, Stafford C, Klinke WP, Martin L, Chan YK, Zaniol D, Rebane T, Abramovich M, Vizel S, Fox B, Kornder J, Breakwell L, Constance C, Gauthier M, Cleveland D, Valley S, Dion D, Morissette A, Vertes G, Ross B, Pandey AS, Byrne M, Abramson B, Sodhi N, Ervin F, Thiessen S, Halperin F, Stedham V, Pesant Y, Sardin V, Saw J, Tarry L, Pouliot J, Marquette S, Belisle P, Gagne D, Ducas J, Munoz A, Sussex B, Newman S, Madan M, Hsu E, Bata I, Cossett J, Glanz A, Vilag C, Paddock V, Collings E, Sabbah E, Chausse I, Fortin C, Lepage C, Chehayeb R, Viau C, Ma P, Seib M, Lamy A, Rizzo A, Rajakumar AR, Eikel L, Nigro F, Stoger S, Welsh R, Lindholm L, Parker JD, Webber S, Winkler L, Hannah G, Gupta M, Kubiak A, Mukherjee A, Bozek B, Nguyen M, Dufort L, Haichin R, Toyota V, Bujold S, Syan G, Chinnasane S, Houde G, Rousseau S, Poirier P, Lariviere M, Dupuis R, Ouimet F, Audet J, Darveau C, Labonte R, Rice T, Nawaz S, Cantor W, Robbins K, Boucher P. Jr, Roberge J, Zadra R, McPherson C, Prieto JC, Noriega V, Cereño C, Mestas M, Yovaniniz P, Ferrada W, Pincetti C, Torres G, Perez L, Villan C, Escobar E, Martin R, Padilla I, Ramirez M, Hormazabal R, Pedemonte O, Suazo E, Hasbun S, Mejias M, Cardenas F, Donoso L, Godoy I, Henriquez P, Mariné L, Vergara T, Juri C, Vergara E, Muñoz M, Solano E, Toro J, Cardenas S, Mendoza F, Martinez S, Saaibi JF, Castillo KM, Ruiz NP, Castillo T, Orozco A, Muñoz C, Martínez J, Lopez D, Ochoa J, Andrade J, Jaramillo C, Garces GP, Botero R, Cáceres A, Jaramillo M, Mejia C, Schlesinger A, Munevar V, Rodriguez J, Granados LM, Jaramillo N, Aristizabal C, Cano N, Salazar JC, Urina M, Manco T, Valenzuela C, Hernandez HJ, Delgado PS, Vagner B, Castaño LA, Ucros P, Tellez M, Delgado JA, Piedrahita CA, Crump J, Fernandez V, Quintero CA, Moreno M, Hernandez Triana E, Cuentas I, Accini JL, Accini M, Manzur F, Rivera E, Reynales H, Huertas D, Hovorka J, Filipovsky J, Hirmerova J, Peska S, Jura R, Kanovsky P, Herzig R, Jansky P, Fiala R, Kalita Z, Gatkova A, Bauer J, Fiksa J, Sedlacek J, Monhart Z, Bren J, Linhart A, Skalicka L, Vitovec J, Hlinomaz O, Parenica J, Soucek M, Rihacek I, Branny M, Sknouril L, Klimsa Z, Holub M, Línkova H, Rektor I, Mikulik R, Mayer O. Sr, Novakova B, Bar M, Brodova P, Polasek R, Sabl P, Kos P, Lorenc Z, Macel I, Graversen KH, Galatius S, Soderberg LH, Sillesen H, Madelung S, Overgård K, Stan V, Rasmussen LH, Mortensen B, Iversen HK, Back C, Olesen C, Christensen H, Pedersen A, Nielsen T, Hasain M, Tanggaard L, Husted S, Christensen LL, Haas L, Mickley H, Hosbond S, Rosenlund I, Jepsen J, Kaspersen BB, Bronnum Schou J, Hempel H, Nyvad O, Feldthaus B, Jensen BS, Jensen MK, Andersen G, Thomsen RB, Rokkedal J, Joergensen A, Bülow M, Jeppesen J, Lederballe O, Scheibel I, Sjol A, Larsen J, Graner M, Svahn T, Melin J, Kaakkomäki A, Airaksinen J, Vasankari T, Tatlisumak T, Metso M, Remes A, Näppä M, Jäkälä P, Sivenius J, Kalinen M, Roine RO, Ketola R, Bassand J, Pales D, Coisne D, Berger N, Galinier M, Rosolin N, Elbaz M, Lacassagne L, Montalescot G, Vignolles N, Gully C, Lepage I, Roynard J, Hamon M, Brucato S, Macquin Mavier I, Beitar T, Berthezene P, Medkour T, Amarenco P, Gueblaoui N, Timsit S, Riou D, Mahagne M, Suissa L, Quere I, Clouzot S, Emmerich J, Martinez I, Moulin T, Cole M, Hosseini H, Monod V, Cottin Y, Bichat F, Galley D, Beltra C, Samson Y, Pires R, Bura Riviere A, Pelvet B, Giroud M, Lecheneaut C, Ohlmann P, Ait m. bark Z, Farah B, Petit F, Caussin C, Braun C, Diehm C, Mehrhof F, Inkrot S, Darius H, Heinze H, Radke P, Kulikowsky C, Ferrari M, Utschig S, Strasser R, Haacke K, Felix SB, Bruder M, Nienaber C, Pfaff H, Sohn H, Baylacher M, Mudra H, Setzer P, Konstantinides S, Hallmann A, Kreuzer J, Tsoy I, Schneider P, Appel KF, Habermeier A, Zeiher AM, Kretschmer T, Mitrovic V, Lehinant S, Bohlscheid V, Palme B, Heuer H, Espinola Klein C, Savvidis S, Kleinertz K, Hänel J, Schmidt E, Schmidt A, Ringleb PA, Ludwig I, Dietzold M, Schaffranka A, Ranft J, Cegla C, Berrouschot J, Stoll A, Tanislav C, Brandtner MA, Rosenkranz M, Otto D, Görtler M, Barleben M, Haberl R, Miedl S, Maschke M, Schröder K, Aral Becher B, Herzog Hauff S, Guenther A, Herzau C, Hoffmann U, Roth Zetzsche S, Grond M, Becker M, Hamann G, Simon K, Köhrmann M, Glahn J, Wuttig H, Nabavi DG, Seraphin D, Schellong S, Frommhold R, Dichgans M, Doerr A, Blessing E, Buss I, Butter C, Bettin D, Grosch B, Blank E, Wong L, Liu R, Lee S, Kong S, Yu C, So E, Jakal Á, Masszi G, Czuriga I, Kapocsi J, Soós E, Csiba L, Fekete K, Valikovics A, Dioszeghy P, Muskóczki E, Csányi A, Matoltsy A, Yuval R, Bornstein N, Elimelech R, Chajek Shaul T, Bursztyn M, Hayek T, Hazbon K, Gavish D, Anat N, Wexler D, Azar P, Mosseri M, Tsirulnikov E, Rozenman Y, Logvinenko S, Tanne D, Don A, Gross B, Feldman Y, Klainman E, Genin Dmitrishin I, Eldar M, Eizenberg N, Atar S, Lasri E, Hammerman H, Aharoni G, Zimlichman R, Zuker S, Telman G, Afanasiev S, Katz A, Biton A, Goldhaber A, Goldhaber M, Elian D, Linor A, Meyuhas S, Tsalihin D, Kissos D, Lampl Y, Israelson M, Gottlieb S, Dotan L, Elis A, Karny M, Hussein O, Shestatski K, Brenner H, Segal E, Baldini U, Gavazzi A, Poloni M, Censori B, Aiazzi L, Maraglino C, Marenzi G, Specchia G, Tritto I, Golino P, CIANFLONE , DOMENICO, Martignoni A, Tamburino C, Rubartelli P, Ardissino D, Tadonio I, Stramba Badiale M, Cernuschi P, Nardulli R, Sommariva L, Giordano A, Berni A, Cavallini C, Fiscella A, Azzarelli S, Esposito G, Cassese S, Danzi G, Fattore L, Barbieri E, De Caterina R, Odero A, Puttini M, Corrada E, Monzini N, Vadalà A, Pistarini C, Scrutinio D, Ferratini M, Marcheselli S, Moretti L, Partemi L, Pupilella T, Lazzari A, Ledda A, Geraci G, Rasura M, Beccia M, Cassadonte F, Vatrano M, Bongiorni D, Mos L, Marcuzzi G, Murena E, Uguccioni L, Ferretti C, Piti ATerrosu P, Perrone PF, Marconi R, Grasso L, Severi S, Evola R, Russo N, Agnelli G, Paci C, Carugo S, Silvestri O, Testa R, Novo S., Braunwald, E, Morrow, Da, Scirica, Bm, Bonaca, Mp, Mccabe, Ch, Morin, S, Fish, P, Lamp, J, Gershman, E, Murphy, S, Deenadayalu, N, Skene, A, Hill, K, Bennett, L, Strony, J, Plat, F, Berman, G, Lipka, L, Kilian, A, He, W, Liu, X, Fox, Ka, Aylward, P, Bassand, Jp, Betriu, A, Bounameaux, H, Corbalan, R, Creager, M, Dalby, A, De Ferrari, G, Dellborg, M, Diehm, Ch, Dietz, R, Goto, S, Grande, P, Gurbel, P, Hankey, G, Isaza, D, Jensen, P, Kiss, R, Lewis, B, Merlini, P, Moliterno, D, Morais, J, Nicolau, Jc, Nieminen, M, Nilsen, D, Olin, J, Ophuis, To, Paolasso, E, Pichler, M, Shinohara, Y, Spinar, J, Teal, P, Tendera, M, Theroux, P, Thomassen, L, Van de Werf, F, White, H, Wilcox, R, Alberts, M, Ameriso, S, Diener, H, Mohr, J, Welch, M, Wiviott, Sd, Awtry, E, Berger, C, Desai, A, Gelfand, E, Ho, C, Leeman, D, Link, M, Norden, A, Pande, A, Rost, N, Ruberg, R, Silverman, S, Singhal, A, Vita, J, Frye, Rl, Bailey, Kr, Easton, J, Hochman, J, Steg, Pg, Verheught, F, Lee, K, Mauro, Do, Centurion, A, Carlevaro, O, Cardozo, E, Cartasegna, L, Soccini, N, Farras, Ha, Molina Aguirre, E, Duronto, E, Arrechavala, L, Rey, R, Stilman, A, Fernández, H, Marinsalta, G, Tartaglione, J, Chekherdemian, M, Povedano, G, Casares, E, Kantor, P, Reges, P, Cuneo, C, Martinez, G, Mackinnon, I, Bagnato, B, Fernandez, A, Funosas, C, Lozada, A, Barilati, P, Ferrari, J, Ferrari, N, Llanos, J, Casaccia, G, Giannaula, R, García Méndez, C, Cirio, J, García Dávila, C, Estol, C, Chiezzo, D, Ramirez, J, Garrido, S, López, M, Hominal, M, Bianchini, Mv, Ramos, M, Verdini, E, Herrera, G, Monne, H, Ioli, P, Samudio, Ma, Rotta Escalante, R, Tarulla, A, Reich, E, Perez, G, Milesi, R, Berli, M, Marino, J, Funes, I, Prado, A, Bezi, M, Fernandez, R, Rojas, M, Cimbaro Canella, Jp, Galarza Salazan, M, Chew, D, Horsfall, L, Claxton, A, French, J, O'Brien, K, Nelson, G, Loxton, A, Mccann, A, Downey, C, Aroney, C, Cleave, P, Worthley, S, Roach, A, Amerena, J, Long, A, Thompson, P, Ferguson, L, Fitzpatrick, M, Mackenzie, M, Youssef, G, Goldsmith, H, Jayasinghe, R, Quinlan, S, Arstall, M, Rose, J, Counsell, J, Martin, M, Crimmins, D, Slattery, A, Anderson, C, Paraskevaidis, T, Davis, S, Silver, G, Gerraty, Rp, Gapper, J, Donnan, G, Petrolo, S, Whelan, A, Tulloch, G, Singh, B, Campo, Ma, Dick, R, Savage, C, Hill, A, Conway, B, Waites, J, Keays, P, Kopp, K, Hainzer, D, Podczeck Schweighofer, A, Priesnitz, T, Drexel, H, Hagspiel, V, Foeger, B, Hilbe, C, Trinka, E, Sinadinoska, D, Pilger, E, Brodmann, M, Stöllberger, C, Jungbauer, Lv, Koppensteiner, R, Hoke, M, Grisold, W, Berger, O, Gaul, Gb, Fazekas, N, Wandaller, C, Stockenhuber, F, Rek, A, Willeit, J, Zangerle, A, Kiechl, S, Sturm, W, Theurl, M, Gruber, F, Schacherl, S, Auer, J, Primus, C, Eber, B, Ammer, M, Hofer, Jf, Mayr, H, Moser, S, Hoellmueller, I, Van der Werf, F, Motte, S, Jorion, M, Schroë, H, Zwinnen, W, Vermassen, F, Geenens, M, De Wolf, L, Briké, C, De Deyn, P, Ongena, P, De Klippel, N, Meeuwissen, K, Desfontaines, P, Tincani, G, Vandermeeren, Y, de Fays, K, Pandolfo, M, Alaerts, N, Peeters, A, Findik, A, Tack, P, Degrande, E, Thijs, V, Marcelis, E, Van Landegem, W, Vanhagendoren, S, Vanhooren, G, Schotte, V, Celen, H, Bes, N, De Letter, J, Holvoet, G, Claerbout, B, Verhamme, P, Debaveye, B, Bourgeois, P, Debrabandere, K, Stalpaert, S, Dhondt, E, De Maeseneire, S, De Bleecker, J, de Koning, K, Vincent, M, Tahon, S, Monté, C, Maes, J, Vossaert, R, Vandenhoven, C, Roosen, J, Vissers, C, Sinnaeve, P, de Velder, L, Thoeng, J, Cauwenberghs, J, Deceuninck, F, Nicolau, J, Ardito, Wr, Queirantes, C, de Araujo Filho, Jd, Ribeiro, Jp, Guizzardi, Sp, Chaves, Ml, Titton, Nf, Pereira, Ah, Webber, I, da Silva DG, Jr, Uehara, Rm, Brasileiro, J, Maia, Ln, Souza, A, Bodanese, Lc, Homem, R, Friedrich, Ma, Macagnan, Ap, Dutra, Op, Brum, Ab, Rossi, Pr, Herek, L, Feitosa, G, Bernardes Ade, S, Braga, J, Rodrigues, D, Guimarães, A, Teixeira, Ab, Marin Neto, Ja, Tonani, M, Piegas, L, Amato, V, Leães, P, Osorio, Rl, Ganem, F, Vieira, Ap, Leao, P, Kanashiro, V, Franken, Ra, Martins, Ep, Gagliardi, Rj, Silva, L, Caffaro, Ra, Novaes, G, Carvalho, A, Laet, Vl, Miranda F., Jr, Crippa, Ba, Saraiva, Jf, Ormundo, Ct, Speciali, Jg, Guandolini, G, de Albuquerque, Dc, Silva, V, Abrantes, Ja, Pinheiro, L, Teixeira, M, Guanaes, Df, Resende, 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Ar, Eikel, L, Nigro, F, Stoger, S, Welsh, R, Lindholm, L, Parker, Jd, Webber, S, Winkler, L, Hannah, G, Gupta, M, Kubiak, A, Mukherjee, A, Bozek, B, Nguyen, M, Dufort, L, Haichin, R, Toyota, V, Bujold, S, Syan, G, Chinnasane, S, Houde, G, Rousseau, S, Poirier, P, Lariviere, M, Dupuis, R, Ouimet, F, Audet, J, Darveau, C, Labonte, R, Rice, T, Nawaz, S, Cantor, W, Robbins, K, Boucher P., Jr, Roberge, J, Zadra, R, Mcpherson, C, Prieto, Jc, Noriega, V, Cereño, C, Mestas, M, Yovaniniz, P, Ferrada, W, Pincetti, C, Torres, G, Perez, L, Villan, C, Escobar, E, Martin, R, Padilla, I, Ramirez, M, Hormazabal, R, Pedemonte, O, Suazo, E, Hasbun, S, Mejias, M, Cardenas, F, Donoso, L, Godoy, I, Henriquez, P, Mariné, L, Vergara, T, Juri, C, Vergara, E, Muñoz, M, Solano, E, Toro, J, Cardenas, S, Mendoza, F, Martinez, S, Saaibi, Jf, Castillo, Km, Ruiz, Np, Castillo, T, Orozco, A, Muñoz, C, Martínez, J, Lopez, D, Ochoa, J, Andrade, J, Jaramillo, C, Garces, Gp, Botero, R, Cáceres, A, Jaramillo, M, Mejia, C, 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Abstract

BACKGROUND:Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1.METHODS:We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage.RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P

Published
2012

14. Aromatase inhibitor pain syndromes: Classification and determination of specific risk factors—A prospective multicenter cohort study.

Author

Cottu, Paul H., primary, Laroche, Francoise, additional, Pierga, Jean-Yves, additional, Coste, J, additional, Medkour, T, additional, Lotz, Jean-Pierre, additional, Beerblock, Karine, additional, Tournigand, Christophe, additional, Chauvenet, Laure, additional, Decleves, Xavier, additional, Boussahira, D, additional, Batteux, F, additional, Borderie, F, additional, and Perrot, Serge, additional

Published
2013
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16. Changes in Descending Pain Modulation During Anti-Tumor Necrosis Factor Therapy: A Prospective Study in Rheumatoid Arthritis and Spondyloarthritis.

Author

Trouvin AP, Simunek A, Coste J, Medkour T, Combier A, Poiroux L, Vidal F, Carvès S, Bouhassira D, and Perrot S

Abstract

Objective: In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of biologic disease-modifying antirheumatic drugs (bDMARDs). The objective of the Rheumatism Pain Inhibitory Descending Pathways study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a tumor necrosis factor inhibitor (TNFi)., Methods: Patients with active disease (50 with RA and 50 with SpA) naive to bDMARDs or targeted synthetic DMARDs and starting a TNFi were included. Patients were observed for six months after TNFi initiation with clinical, psychological, and pain assessment. At all visits, participants underwent quantitative sensory testing with heat and cold pain thresholds and descending inhibition by conditioned pain modulation (CPM). Descending pain control (CPM effect) was assessed as the change in heat pain threshold (°C) following a conditioning stimulus., Results: Of the 100 patients (59 women, mean ± SD age 45.8 ± 14.6 years), 74 completed the six-month follow-up. Thermal pain thresholds did not significantly change during follow-up. CPM effect improved significantly during follow-up (mean ± SD 0.25 ±2.57°C at baseline and 2.96 ± 2.50°C at six months; P < 0.001). At the end of follow-up, the mean CPM effect was significantly higher in patients without significant pain compared with patients with persistent pain (>3 of 10 on the Brief Pain Inventory) (mean ± SD 3.25 ± 2.68°C vs 2.47 ± 2.11°C; P = 0.04) and in patients achieving remission or low disease activity compared with patients with active rheumatism (mean ± SD 3.31 ± 2.68°C vs 2.18 ± 1.87°C; P = 0.01)., Conclusion: In active inflammatory rheumatisms, impaired descending pain modulation, but not thermal pain thresholds, is improved after TNFi treatment, suggesting a possible effect of TNFi on central pain modulation., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Published
2024
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17. A systematic literature review on patient-reported outcome domains and measures in nonsurgical efficacy trials related to chronic pain associated with endometriosis: an urgent call to action.

Author

Rosenberger DC, Mennicken E, Schmieg I, Medkour T, Pechard M, Sachau J, Fuchtmann F, Birch J, Schnabel K, Vincent K, Baron R, Bouhassira D, and Pogatzki-Zahn EM

Subjects
Humans, Female, Pelvic Pain therapy, Pelvic Pain etiology, Quality of Life, Treatment Outcome, Endometriosis complications, Endometriosis therapy, Endometriosis psychology, Patient Reported Outcome Measures, Chronic Pain therapy, Chronic Pain psychology
Abstract

Abstract: Endometriosis, a common cause for chronic pelvic pain, significantly affects quality of life, fertility, and overall productivity of those affected. Therapeutic options remain limited, and collating evidence on treatment efficacy is complicated. One reason could be the heterogeneity of assessed outcomes in nonsurgical clinical trials, impeding meaningful result comparisons. This systematic literature review examines outcome domains and patient-reported outcome measures (PROMs) used in clinical trials. Through comprehensive search of Embase, MEDLINE, and CENTRAL up until July 2022, we screened 1286 records, of which 191 were included in our analyses. Methodological quality (GRADE criteria), information about publication, patient population, and intervention were assessed, and domains as well as PROMs were extracted and analyzed. In accordance with IMMPACT domain framework, the domain pain was assessed in almost all studies (98.4%), followed by adverse events (73.8%). By contrast, assessment of physical functioning (29.8%), improvement and satisfaction (14.1%), and emotional functioning (6.8%) occurred less frequently. Studies of a better methodological quality tended to use more different domains. Nevertheless, combinations of more than 2 domains were rare, failing to comprehensively capture the bio-psycho-social aspects of endometriosis-associated pain. The PROMs used showed an even broader heterogeneity across all studies. Our findings underscore the large heterogeneity of assessed domains and PROMs in clinical pain-related endometriosis trials. This highlights the urgent need for a standardized approach to both, assessed domains and high-quality PROMs ideally realized through development and implementation of a core outcome set, encompassing the most pivotal domains and PROMs for both, stakeholders and patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Published
2024
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18. Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation.

Author

Trouvin AP, Simunek A, Coste J, Medkour T, Carvès S, Bouhassira D, and Perrot S

Subjects
Humans, Conditioning, Psychological physiology, Pain Threshold physiology, Pain Measurement psychology, Chronic Pain etiology, Rheumatic Fever, Arthritis, Rheumatoid complications
Abstract

Abstract: Persistent pain despite satisfactory disease treatment is frequent in rheumatoid arthritis (RA) and spondyloarthritis (Spa) and may result from specific changes in central pain processing. We assessed these mechanisms further by systematically comparing thermal pain thresholds and conditioned pain modulation (CPM) between patients with active RA or Spa and healthy controls. We included 50 patients with RA and 50 patients with Spa and 100 age-matched and sex-matched controls. Heat and cold pain thresholds (HPT-CPT) were measured on the dominant forearm, and CPM was assessed by applying conditioning stimuli (immersion in a cold-water bath) to one foot and the nondominant hand in 2 successive randomized sequences. Descending pain modulation was assessed as the difference in HPTs (in °C) before and after conditioning. Larger HPT differences (ie, a larger CPM effect) reflected more efficient descending inhibition. Potential associations between changes in CPM and clinical data, including disease activity, pain intensity, and psychological and functional variables, were systematically assessed. Heat pain threshold and cold pain threshold were similar in patients and controls. The mean CPM effect was significantly weaker in patients than that in controls for conditioning applied to either the foot (0.25°C ±2.57 vs 2.79°C ±2.31; P < 0.001) or the nondominant hand (0.57°C ±2.74 vs 2.68°C ±2.12; P < 0.001). The smaller CPM effect in patients was correlated with average pain intensity, but not with disease activity or other clinical characteristics, suggesting a significant pathophysiological role for changes in endogenous pain modulation in the mechanisms of chronic pain associated with inflammatory rheumatism., (Copyright © 2022 International Association for the Study of Pain.)

Published
2023
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19. Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials - A Systematic Literature Review.

Author

Sachau J, Sendel M, Péchard M, Schnabel K, Schmieg I, Medkour T, Ecochard L, Woischnik M, Liedgens H, Pogatzki-Zahn E, Baron R, and Bouhassira D

Subjects
Humans, Treatment Outcome, Outcome Assessment, Health Care, Patient Reported Outcome Measures, Neuralgia drug therapy, Chronic Pain drug therapy
Abstract

In neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains 'physical functioning', 'global improvement and satisfaction', and 'neuropathic pain quality' were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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20. "FastSchool": A single session of an interprofessional pain management program for chronic pain patients inspired by cognitive behavioral therapy.

Author

Trouvin AP, Carvès S, Rouquette A, Coste J, Meyer S, Colin F, Deleens R, Medkour T, Collet MP, Perrot S, and Laroche F

Subjects
Humans, Pain Management methods, Analgesics, Opioid, Catastrophization psychology, Chronic Pain therapy, Chronic Pain psychology, Cognitive Behavioral Therapy methods
Abstract

Objectives: Multidisciplinary approaches to treating chronic pain have been proven effective. Currently, chronic pain patients face lengthy waitlists in pain medicine departments. To overcome this problem, we developed the "FastSchool" program to educate patients about pain management and treatment. In this study, we evaluated the benefit of a "FastSchool" session on pain and catastrophizing in chronic pain patients., Methods: Included patients had chronic non-cancer pain, no more than 2 visits to a pain medicine department. Patients attended a single 3-hour session, conducted by an interprofessional team. Four topics were addressed: chronic pain mechanisms, pharmacological therapies, physical activity, and the management of analgesics. Patients completed questionnaires at baseline and at 3 months post-session to assess pain interference, pain intensity, and catastrophizing., Results: The study population included 88 patients; 71 completed the follow-up questionnaires. Pain interference (p = 0.002), average pain intensity (p = 0.013), and catastrophizing (p < 0.001) decreased 3 months after FastSchool. At M3, 35 % of patients felt their pain had improved based on the Patient Global Impression of Change., Conclusion: FastSchool, an innovative short-term educational program inspired by cognitive behavioral therapy, showed positive results in reducing pain impact., Practice Implications: Implementation of FastSchool in pain medicine departments would reduce waitlist times for non-pharmacological treatment., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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21. Response to Alvarez et al.

Author

Coste J, Medkour T, Maigne JY, Pérez M, Laroche F, and Perrot S

Abstract

Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2021
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22. Osteopathic medicine for fibromyalgia: a sham-controlled randomized clinical trial.

Author

Coste J, Medkour T, Maigne JY, Pérez M, Laroche F, and Perrot S

Abstract

Background: Patients with fibromyalgia (FM) frequently resort to osteopathic or chiropractic treatment, despite very weak supporting evidence. We aimed to assess the efficacy of osteopathic manipulation in FM in a properly controlled and powered randomized clinical trial., Methods: Patients were randomized to osteopathic or sham treatment. Treatment was administered by experienced physical medicine physicians, and consisted of six sessions per patient, over 6 weeks. Treatment credibility and expectancy were repeatedly evaluated. Patients completed standardized questionnaires at baseline, during treatment, and at 6, 12, 24, and 52 weeks after randomization. The primary outcome was pain intensity (100-mm visual analog scale) during the treatment period. Secondary outcomes included fatigue, functioning, and health-related quality of life. We performed primarily intention-to-treat analyses adjusted for credibility, using multiple imputation for missing data., Results: In total, 101 patients (94% women) were included. Osteopathic treatment did not significantly decrease pain relative to sham treatment (mean difference during treatment: -2.2 mm; 95% confidence interval, -9.1 to 4.6 mm). No significant differences were observed for secondary outcomes. No serious adverse events were observed, despite a likely rebound in pain and altered functioning at week 12 in patients treated by osteopathy. Patient expectancy was predictive of pain during treatment, with a decrease of 12.9 mm (4.4-21.5 mm) per 10 points on the 0-30 scale. Treatment credibility and expectancy were also predictive of several secondary outcomes., Conclusion: Osteopathy conferred no benefit over sham treatment for pain, fatigue, functioning, and quality of life in patients with FM. These findings do not support the use of osteopathy to treat these patients. More attention should be paid to the expectancy of patients in FM management., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Published
2021
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23. A Lasso quantile periodogram based feature extraction for EEG-based motor imagery.

Author

Meziani A, Djouani K, Medkour T, and Chibani A

Subjects
Adult, Humans, Algorithms, Brain-Computer Interfaces, Electroencephalography methods, Imagination, Motor Activity, Neurosciences methods, Signal Processing, Computer-Assisted
Abstract

Background: The extraction of relevant and distinct features from the electroencephalogram (EEG) signals is one of the most challenging task when implementing Brain Computer Interface (BCI) based systems. Frequency analysis techniques are recognised as one of the most suitable methods to have distinct information from EEG signals. However, existing studies use mostly classical approaches assuming that the signal is Gaussian, stationary and linear. These properties are not verified in the EEG case considering the complexity of the brain electrical activity., New Method: This paper proposes two new spectral estimators that are robust against non-Gaussian, non-linear and non-stationary signals. These two approaches use quantile regression and L 1 -norm regularisation to estimate the spectrum of the motor imagery (MI) related EEG., Results: A dataset collected during a study of BCI motor imagery project conducted at Tshwane University of Technology (TUT), Pretoria, South Africa, is used to validate the proposed estimators. Experimental results demonstrate that the newly proposed approaches help improve the classification performance of MI., Comparison With Existing Methods: In order to show the effectiveness of the proposed estimators, a comparative study is conducted, considering classical commonly used techniques such as FFT and Welch periodogram through 5 classification algorithms., Conclusions: The proposed Quantile-based spectral estimators are potential methods to improve the classification performance of the EEG-Based motor imagery systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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24. Quality of life and impact of pain in women treated with aromatase inhibitors for breast cancer. A multicenter cohort study.

Author

Laroche F, Perrot S, Medkour T, Cottu PH, Pierga JY, Lotz JP, Beerblock K, Tournigand C, Chauvenet L, Bouhassira D, and Coste J

Subjects
Cohort Studies, Confidence Intervals, Female, Follow-Up Studies, Humans, Middle Aged, Regression Analysis, Aromatase Inhibitors therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms psychology, Quality of Life psychology
Abstract

Women with hormone-dependent breast cancer are treated with aromatase inhibitors (AI) to slow disease progression by decreasing estrogen levels. However, AI have adverse effects, including pain, with potentially serious impact on quality of life (QOL) and treatment compliance. We evaluated quality of life during the first year of AI treatment, focusing particularly on the impact of pain. In a multicenter cohort study of 135 women with early-stage breast cancer, free of pain at the initiation of AI treatment, quality of life (by the EORTC QLQ-BR23), somatic and psychic symptoms, psychological characters, temperament and coping strategies were assessed at baseline and at each follow-up visit (1, 3, 6 and 12 months). The impact of treatment-induced pain on quality of life during follow-up was determined with repeated-measures regression models. These models were constructed to assess the effects of pain and pain type on quality of life during follow-up, taking into account predictors associated with quality of life at baseline. Prior ganglion resection, taxane treatment and chemotherapy, a high amplification score on the pain catastrophizing scale, and a high harm avoidance score on the personality questionnaire were associated with a significantly lower baseline QOL. Fifty-seven percent of women developed pain of five different types: upper or lower limb joint pain, diffuse pain, neuropathic pain, tendon pain and mixed pain. A significant decrease in QOL was noted in the women with pain, particularly for body image, sexual functioning and future perspectives. Moreover, the impact of pain on QOL depended on the type of pain experienced. In conclusion, women treated with aromatase inhibitors display changes in quality of life and the degree of change in quality of life depends mostly on the type of pain experienced. Oncologists and patients should be aware of painful adverse effects of AI and encouraged to provide or receive earlier and more appropriate management of these effects.

Published
2017
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25. Napping reverses increased pain sensitivity due to sleep restriction.

Author

Faraut B, Léger D, Medkour T, Dubois A, Bayon V, Chennaoui M, and Perrot S

Subjects
Adult, Cross-Over Studies, Humans, Male, Pain diagnosis, Pain etiology, Polysomnography, Time Factors, Pain Threshold, Sleep, Sleep Deprivation
Abstract

Study Objective: To investigate pain sensitivity after sleep restriction and the restorative effect of napping., Design: A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed., Setting: Laboratory-based study., Participants: 11 healthy male volunteers., Interventions: Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon., Measurements and Results: Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area., Conclusions: Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

Published
2015
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26. Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study.

Author

Laroche F, Coste J, Medkour T, Cottu PH, Pierga JY, Lotz JP, Beerblock K, Tournigand C, Declèves X, de Cremoux P, Bouhassira D, and Perrot S

Subjects
Aged, Analgesics therapeutic use, Aromatase Inhibitors therapeutic use, Arthralgia chemically induced, Arthralgia diagnosis, Arthralgia physiopathology, Breast Neoplasms physiopathology, Estrogens, Female, Follow-Up Studies, Humans, Neuralgia chemically induced, Neuralgia diagnosis, Neuralgia physiopathology, Pain diagnosis, Pain physiopathology, Prognosis, Prospective Studies, Risk Factors, Syndrome, Tendinopathy chemically induced, Tendinopathy diagnosis, Tendinopathy physiopathology, Aromatase Inhibitors adverse effects, Breast Neoplasms drug therapy, Pain chemically induced
Abstract

Unlabelled: Aromatase inhibitors (AIs) are the first-line treatment in women with breast cancer for total estrogen depletion. Half the treated women may develop pain, and this condition may therefore be seen as a clinical model of pain related to estrogen deprivation. In this prospective multicenter study, we classified AI-related pain syndromes and identified their predictors. A 1-year, prospective, multicenter cohort study, with 6 visits, was carried out on 135 women with early-stage breast cancer and no pain at the start of AI treatment. At initial assessment, we investigated clinical (demographic and psychosocial, cancer characteristics and treatment, sleep, quality of life), biological (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunologic and inflammatory markers), environmental, and genetic (polymorphism for pain mechanisms) risk factors for pain. During 1 year of follow-up, 77 women (57%) developed pain, leading to AI discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%), diffuse pain (22%), tendinitis (22%), neuropathic pain (9%), and mixed pain (11%), which are mostly persistent (57%), with diffuse and joint pains the most intense. Risk factors for the development of pain included higher levels of anxiety and impaired quality of life at the initial assessment, whereas cancer characteristics, genetic background, inflammation, and immunologic and hormonal status at baseline were not significant predictors., Perspective: This article presents a classification of AI-related pain syndromes induced by estrogen deprivation that were previously described as arthralgia, but not as neuropathic, diffuse, and mixed pain. This estrogen deprivation-related condition represents a clinical model of pain, and our study identified mostly psychological risk factors for pain development., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Published
2014
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27. The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with experimental data.

Author

Medkour T, Ferrone F, Galactéros F, and Hannaert P

Subjects
Humans, Biopolymers chemistry, Hemoglobin, Sickle chemistry, Models, Biological
Abstract

Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591-610, 611-631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink), The MathWorks). Here, we compare the simulated outputs to experimental progress curves (n = 6-8 different [HbS], 3-6 mM range, from Ferrone's group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 +/- 0.01 (25 degrees C, n = 8; mean +/- standard error). Conversely, for complete progress curves, averaged rms is 0.48 +/- 0.04. This figure is improved to 0.13 +/- 0.01 by adjusting heterogeneous pathway parameters (p < 0.01): the nucleus stability (sigma(2) micro( cc ): + 40%), and the fraction of polymer surface available for nucleation (phi), from 5e(-7), (3 mM) to 13 (6 mM). Similar results are obtained at 37 degrees C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process.

Published
2008
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