BMC cancer
Authors: Torres-Mejía G, Smith RA, Carranza-Flores Mde L, Bogart A, Martínez-Matsushita L, Miglioretti DL, Kerlikowske K, Ortega-Olvera C, Montemayor-Varela E, Angeles-Llerenas A, Bautista-Arredondo S, Sánchez-González G, Martínez-Montañez OG, Uscanga-Sánchez SR, Lazcano-Ponce E, Hernández-Ávila M
Volume 68 of Issue 4 | European urology
Authors: Saad F, Shore N, Van Poppel H, Rathkopf DE, Smith MR, de Bono JS, Logothetis CJ, de Souza P, Fizazi K, Mulders PF, Mainwaring P, Hainsworth JD, Beer TM, North S, Fradet Y, Griffin TA, De Porre P, Londhe A, Kheoh T, Small EJ, Scher HI, Molina A, Ryan CJ
BACKGROUND
Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.
OBJECTIVE
Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients.
DESIGN, SETTING, AND PARTICIPANTS
This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
INTERVENTION
Patients were grouped by concomitant BTT use or no BTT use.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.
RESULTS AND LIMITATIONS
While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.
CONCLUSIONS
AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.
PATIENT SUMMARY
Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00887198.
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Journal of medical genetics
Authors: van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC
Clinical journal of the American Society of Nephrology : CJASN
Authors: Bansal N, Shlipak MG
AIDS (London, England)
Authors: Henrich TJ, Hanhauser E, Hu Z, Stellbrink HJ, Noah C, Martin JN, Deeks SG, Kuritzkes DR, Pereyra F
American journal of respiratory and critical care medicine
Authors: Steiling K, Christenson SA
Volume 130 of Issue 2 | Acta neuropathologica
Authors: Nobuta H, Cilio MR, Danhaive O, Tsai HH, Tupal S, Chang SM, Murnen A, Kreitzer F, Bravo V, Czeisler C, Gokozan HN, Gygli P, Bush S, Weese-Mayer DE, Conklin B, Yee SP, Huang EJ, Gray PA, Rowitch D, Otero JJ
Human congenital central hypoventilation syndrome (CCHS), resulting from mutations in transcription factor PHOX2B, manifests with impaired responses to hypoxemia and hypercapnia especially during sleep. To identify brainstem structures developmentally affected in CCHS, we analyzed two postmortem neonatal-lethal cases with confirmed polyalanine repeat expansion (PARM) or Non-PARM (PHOX2B∆8) mutation of PHOX2B. Both human cases showed neuronal losses within the locus coeruleus (LC), which is important for central noradrenergic signaling. Using a conditionally active transgenic mouse model of the PHOX2B∆8 mutation, we found that early embryonic expression (
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Volume 14 | Malaria journal
Authors: Boyce RM, Muiru A, Reyes R, Ntaro M, Mulogo E, Matte M, Siedner MJ
BACKGROUND
The World Health Organization recommends that all suspected malaria cases receive a parasitological diagnosis prior to treatment with artemisinin-based combination therapy. A recent meta-analysis of clinical trials evaluating RDTs for the management of patients with fever found substantial reductions in anti-malarial prescriptions when health workers adhered to treatment protocols based on test results. However few studies have reported on the impact of RDTs on health systems outside research settings.
METHODS
The study comprised a retrospective interrupted time series analysis, comparing rates of malaria diagnosis, treatment, and resource utilization before and after introduction of RDTs at a peripheral health facility in rural Western Uganda. The use of malaria diagnostic tests was graphically depicted throughout the study period and fit regression models to identify correlates of three outcomes of interest: (1) length of stay (2) the proportion of patients referred to a higher-level health facility, and (3) administration of antibiotics.
RESULTS
Over the course of the study period, 14,357 individuals underwent diagnostic testing for malaria with either a RDT (9,807) or microscopy (4,550). The proportion of patients with parasite-based diagnoses more than tripled to 34% after the introduction of RDTs. RDTs largely replaced microscopy as the diagnostic method of choice. Compared to patients admitted during the pre-RDT period, patients admitted to the health centre with malaria in the post-RDT period had significantly reduced odds of being referred to another health centre (AOR=0.49, P=0.038), receiving antibiotics (AOR=0.42, P<0.001), and a significantly shorter mean length of stay (β=-0.32 days, 95%CI -0.52 to -0.13).
CONCLUSIONS
This study is one of the few to demonstrate significant improvement in clinical outcomes and process measures following the introduction of RDTs for the diagnosis of malaria at a rural health facility in Uganda. The results show a reduction in referrals and shorter mean inpatient LOS even as antibiotics were prescribed less frequently. This change greatly increased laboratory throughput and the resultant proportion of patients receiving a parasite-based diagnosis.
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The European physical journal. C, Particles and fields
Authors: Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Erö J, Friedl M, Frühwirth R, Ghete VM, Hartl C, Hörmann N, Hrubec J, Jeitler M, Kiesenhofer W, Knünz V, Krammer M, Krätschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schöfbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Suarez Gonzalez J, Alderweireldt S, Bansal S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Léonard A, Mohammadi A, Perniè L, Randle-Conde A, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Zenoni F, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Fagot A, Garcia G, Mccartin J, Ocampo Rios AA, Poyraz D, Ryckbosch D, Salva Diblen S, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Vidal Marono M, Vizan Garcia JM, Beliy N, Caebergs T, Daubie E, Hammad GH, Júnior WLA, Alves GA, Brito L, Correa Martins Junior M, Martins TDR, Molina J, Mora Herrera C, Pol ME, Teles PR, Carvalho W, Chinellato J, Custódio A, Da Costa EM, De Jesus Damiao D, De Oliveira Martins C, Fonseca De Souza S, Malbouisson H, Matos Figueiredo D, Mundim L, Nogima H, Prado Da Silva WL, Santaolalla J, Santoro A, Sznajder A, Tonelli Manganote EJ, Vilela Pereira A, Bernardes CA, Dogra S, Fernandez Perez Tomei TR, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Hadjiiska R, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Tao J, Wang Z, Asawatangtrakuldee C, Ban Y, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zhang F, Zhang L, Zou W, Avila C, Cabrera A, Chaparro Sierra LF, Florez C, Gomez JP, Gomez Moreno B, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Mekterovic D, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, Assran Y, Ellithi Kame A, Mahmoud MA, Radi A, Kadastik M, Murumaa M, Raidal M, Tiko A, Eerola P, Voutilainen M, Härkönen J, Heikkilä JK, Karimäki V, Kinnunen R, Kortelainen MJ, Lampén T, Lassila-Perini K, Lehti S, Lindén T, Luukka P, Mäenpää T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Givernaud A, Gras P, Hamel de Monchenault G, Jarry P, Locci E, Malcles J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Chapon E, Charlot C, Dahms T, Dobrzynski L, Filipovic N, Florent A, Granier de Cassagnac R, Mastrolorenzo L, Miné P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gelé D, Goerlach U, Goetzmann C, Le Bihan AC, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Bernet C, Boudoul G, Bouvier E, Brochet S, Carrillo Montoya CA, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Ruiz Alvarez JD, Sabes D, Sgandurra L, et al
Physical review letters
Authors: Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Erö J, Friedl M, Frühwirth R, Ghete VM, Hartl C, Hörmann N, Hrubec J, Jeitler M, Kiesenhofer W, Knünz V, Krammer M, Krätschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schöfbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Suarez Gonzalez J, Alderweireldt S, Bansal S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay AP, Grebenyuk A, Léonard A, Mohammadi A, Perniè L, Randle-Conde A, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Zenoni F, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Fagot A, Garcia G, Mccartin J, Ocampo Rios AA, Poyraz D, Ryckbosch D, Salva Diblen S, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Vidal Marono M, Vizan Garcia JM, Beliy N, Caebergs T, Daubie E, Hammad GH, Aldá Júnior WL, Alves GA, Brito L, Correa Martins Junior M, Dos Reis Martins T, Molina J, Mora Herrera C, Pol ME, Rebello Teles P, Carvalho W, Chinellato J, Custódio A, Da Costa EM, De Jesus Damiao D, De Oliveira Martins C, Fonseca De Souza S, Malbouisson H, Matos Figueiredo D, Mundim L, Nogima H, Prado Da Silva WL, Santaolalla J, Santoro A, Sznajder A, Tonelli Manganote EJ, Vilela Pereira A, Bernardes CA, Dogra S, Tomei TR, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Hadjiiska R, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Tao J, Wang Z, Asawatangtrakuldee C, Ban Y, Guo W, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zhang F, Zhang L, Zou W, Avila C, Cabrera A, Chaparro Sierra LF, Florez C, Gomez JP, Gomez Moreno B, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Mekterovic D, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, Assran Y, Ellithi Kamel A, Mahmoud MA, Radi A, Kadastik M, Murumaa M, Raidal M, Tiko A, Eerola P, Voutilainen M, Härkönen J, Karimäki V, Kinnunen R, Kortelainen MJ, Lampén T, Lassila-Perini K, Lehti S, Lindén T, Luukka P, Mäenpää T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Givernaud A, Gras P, Hamel de Monchenault G, Jarry P, Locci E, Malcles J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Chapon E, Charlot C, Dahms T, Dobrzynski L, Filipovic N, Florent A, Granier de Cassagnac R, Mastrolorenzo L, Miné P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gelé D, Goerlach U, Goetzmann C, Le Bihan AC, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Bernet C, Boudoul G, Bouvier E, Brochet S, Carrillo Montoya CA, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Ruiz Alvarez JD, Sabes D, Sgandurra L, Sordini V, et al