23 results on '"Donnelly, J Peter"'
Search Results
2. Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis.
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Brown L, Rautemaa-Richardson R, Mengoli C, Alanio A, Barnes RA, Bretagne S, Chen SCA, Cordonnier C, Donnelly JP, Heinz WJ, Jones B, Klingspor L, Loeffler J, Rogers TR, Rowbotham E, White PL, and Cruciani M
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- Humans, Polymerase Chain Reaction methods, Sputum microbiology, Respiratory System microbiology, Pneumocystis carinii genetics, Pneumocystis carinii isolation & purification, HIV Infections diagnosis, Real-Time Polymerase Chain Reaction methods, Pneumonia, Pneumocystis diagnosis, Pneumonia, Pneumocystis microbiology, Immunocompromised Host, Sensitivity and Specificity, Bronchoalveolar Lavage Fluid microbiology
- Abstract
Background: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations., Methods: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined., Results: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients., Conclusions: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested., Competing Interests: Potential conflicts of interest. A. A. has received honoraria from Gilead Sciences. S. C.-A. A. has received united educational grants from F2G Ltd and consulted for MSD Australia. T. R. R. has received grants from Pfizer and the Irish Department of Agriculture, Food and the Marine and honoraria from Gilead and Menarini Pharma. P. L. W. has performed diagnostic evaluations and received meeting sponsorship from Associates of Cape Cod, Bruker, Dynamiker, and Launch Diagnostics; speaker fees, expert advice fees, and meeting sponsorship from Gilead; and speaker and expert advice fees from F2G. J. P. D. has received personal fees from F2G, Gilead Sciences, and Pfizer. W. J. H. has received lecture honoraria from AbbVie, Amgen, AstraZeneca, Celgene/BMS, Gilead Sciences, Janssen, MSD, and Pfizer; has received support to attend meetings and travel support from AbbVie, Alexion, Astellas, Janssen, Lilly, MSD, Novartis, and Pfizer; and has participated on advisory boards for AbbVie, Amgen, AstraZeneca, Basilea, Celgene/BMS, Gilead Sciences, Janssen, and Sanofi-Aventis. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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3. Polymerase Chain Reaction of Plasma and Bronchoalveolar Lavage Fluid for Diagnosing Invasive Aspergillosis.
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White PL and Donnelly JP
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- Humans, Bronchoalveolar Lavage Fluid, Aspergillus genetics, Mannans blood, Polymerase Chain Reaction, Aspergillosis diagnosis, Cell-Free Nucleic Acids
- Abstract
Competing Interests: Potential conflicts of interest. P. L. W. performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; speaker's fees, expert advice fees, and meeting sponsorship from Gilead; speaker’s and expert advice fees from F2G and speaker’s fees from MSD and Pfizer: speaker's fees and performed diagnostic evaluations for Associates of Cape Cod and IMMY; speaker’s fees from Qiagen; expert advice fees from Mundipharma; is a founding member of the Fungal PCR Initiative and involved with developing the Aspergillus PCR criterion in the 2020 EORTC/MSGERC definitions. J. P. D. is a consultant for F2G, Gilead Sciences, and Shionogi Europe BV and is a founding member of the Fungal PCR Initiative. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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- 2023
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4. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer.
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Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, Turlure P, Selleslag D, Baron F, Aoun M, Heinz WJ, Bertz H, Ráčil Z, Vandercam B, Drgona L, Coiteux V, Llorente CC, Schaefer-Prokop C, Paesmans M, Ameye L, Meert L, Cheung KJ, Hepler DA, Loeffler J, Barnes R, Marchetti O, Verweij P, Lamoth F, Bochud PY, Schwarzinger M, and Cordonnier C
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- Humans, Antifungal Agents therapeutic use, Fluconazole therapeutic use, Caspofungin therapeutic use, Mycoses drug therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute drug therapy, Myelodysplastic Syndromes
- Abstract
Background: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown., Methods: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization., Results: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001)., Conclusions: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27., Competing Interests: Potential conflicts of interest. J. M. reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Gilead Sciences, and Pfizer, including participation on a data and safety monitoring board or advisory board (DSMB) for MSD, Gilead, and Pfizer. T. L. reports payment for participation on virtual European Society for Blood and Marrow Transplantation meeting. J. P. D. reports consulting fees from F2G and Gilead Sciences, including payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from F2G, Gilead Sciences, and Pfizer, and unpaid leadership or fiduciary role in other board, society, committee, or advocacy group for the European PCR Initiative Foundation. C. R. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead and Sandoz and support for attending meetings and/or travel for Gilead, MSD, Pfizer, and Sandoz. N. B. reports participation as the chair on a DSMB for the SHORT trial and roles as the president of the Dutch Society of Hematology (unpaid), Treasurer Board member for HOVON (unpaid), chair of the Horizonscan WP Hematology Dutch Healthcare Institute (vacancy fee), and member of the board of supervisors for Matchis (compensation according to Dutch law). D. S. reports grants or contracts from Pfizer, Novartis, BMS, AbbVie, MSD, and Takeda, including consulting fees from Pfizer, Novartis, AbbVie, BMS, Takeda, MSD, Janssen-Cilag, and Astellas; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer, Novartis, AbbVie, BMS, Takeda, MSD, and Janssen-Cilag; support for attending meetings and/or travel from Pfizer, Novartis, BMS, AbbVie, Takeda, MSD, and Janssen-Cilag; and a leadership or fiduciary role for other board, society, committee, or advocacy groups, paid or unpaid for Belgian College for Reimbursement of Orphan Drugs. F. B. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie and Sanofi; support for attending an international meeting from Novartis and Pfizer; and participation on a DSMB or advisory board for some academic studies (no fee) and Maatpharma (paid to institution). W. J. H. reports payment or honoraria for presentations from AbbVie, Amgen, AstraZeneca, Celgene/BMS, Gilead Sciences, and Janssen; support for attending meetings from IPSEN Pharma, Amgen, and Abbvie; and support for attending adboards for Amgen, Astrazeneca, Celgene/BMS, Gilead Sciences Janssen, MSD, and Sanofi-Aventis. B. V. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer, Sanofi, and Al Miral; support for attending meetings and/or travel for ViiV; and participation on a DSMB or advisory board for Pfizer. L. D. reports consulting fees from MSD, Pfizer, and Teva; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Pfizer, Teva, and Sandoz; support for attending meetings and/or travel from Sandoz; and participation on an advisory board for Pfizer. C. C. L. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead and Kite and support for attending meetings and/or travel for Gilead and Kite. C. S. P. reports book royalties from Elsevier and Thieme and honoraria for lectures from Canon Medical Systems. R. B. reports consulting fees from Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead; and support for attending meetings and/or travel for Gilead. P. E. V. reports research grants from ZonMw, Welcome Trust, Eurostars, EORTC, and RIVM; consulting fees from F2G, Gilead Sciences, and Pfizer; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead Sciences and Pfizer. F. L. reports research grants from Merck, Sharpe & Dohme, Gilead, Pfizer, and Novartis and consulting fees (advisory board) from Gilead and Pfizer. P. Y. B. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead Sciences Switzerland AG and Pfizer PFE Switzerland GmbH and support for Gilead Sciences Switzerland Sarl for TIMM, Trends in Medical Mycology. D. H. reports employment with Merck & Co. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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5. Correction to: Epidemiology and Outcome of Fungemia in a Cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).
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Cornely OA, Gachot B, Akan H, Bassetti M, Uzun O, Kibbler C, Marchetti O, de Burghgraeve P, Ramadan S, Pylkkanen L, Ameye L, Paesmans M, and Donnelly JP
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- 2022
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6. The Evidence Supporting the Revised EORTC/MSGERC Definitions for Invasive Fungal Infections.
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Pappas PG, Chen SC, and Donnelly JP
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- Antifungal Agents therapeutic use, Humans, Aspergillosis drug therapy, Invasive Fungal Infections diagnosis, Invasive Fungal Infections drug therapy
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- 2021
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7. Reply to Herbrecht et al.
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Baddley JW, Morrissey CO, Shaefer-Prokop C, Chen SC, Pappas PG, and Donnelly JP
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- Consensus, Humans, Invasive Fungal Infections, Neoplasms
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- 2020
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8. Reply to Luppi et al.
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Wingard JR, Maertens J, Pagano L, Chen SC, Pappas PG, and Donnelly JP
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- Consensus, Humans, Invasive Fungal Infections, Mycoses, Neoplasms
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- 2020
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9. Reply to Mafaciolli and Pasqualotto.
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Verweij PE, Maertens J, Chen SC, Pappas PG, and Donnelly JP
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- Consensus, Humans, Mycoses, Neoplasms
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- 2020
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10. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.
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Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, and Pappas PG
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- Antifungal Agents therapeutic use, Consensus, Humans, Immunocompromised Host, Invasive Fungal Infections diagnosis, Invasive Fungal Infections drug therapy, Mycoses diagnosis, Mycoses drug therapy, Mycoses epidemiology, Neoplasms drug therapy
- Abstract
Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential., Methods: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved., Results: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses., Conclusions: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2020
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11. Aspergillus Polymerase Chain Reaction: Systematic Review of Evidence for Clinical Use in Comparison With Antigen Testing.
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White PL, Wingard JR, Bretagne S, Löffler J, Patterson TF, Slavin MA, Barnes RA, Pappas PG, and Donnelly JP
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- Aspergillosis diagnosis, Aspergillus immunology, Galactose analogs & derivatives, Humans, Mannans analysis, Quality Control, Sensitivity and Specificity, beta-Glucans analysis, Antigens, Fungal analysis, Aspergillus genetics, Aspergillus isolation & purification, Immunoenzyme Techniques statistics & numerical data, Polymerase Chain Reaction standards, Polymerase Chain Reaction statistics & numerical data
- Abstract
Background: Aspergillus polymerase chain reaction (PCR) was excluded from the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal disease because of limited standardization and validation. The definitions are being revised., Methods: A systematic literature review was performed to identify analytical and clinical information available on inclusion of galactomannan enzyme immunoassay (GM-EIA) (2002) and β-d-glucan (2008), providing a minimal threshold when considering PCR. Categorical parameters and statistical performance were compared., Results: When incorporated, GM-EIA and β-d-glucan sensitivities and specificities for diagnosing invasive aspergillosis were 81.6% and 91.6%, and 76.9% and 89.4%, respectively. Aspergillus PCR has similar sensitivity and specificity (76.8%-88.0% and 75.0%-94.5%, respectively) and comparable utility. Methodological recommendations and commercial PCR assays assist standardization. Although all tests have limitations, currently, PCR is the only test with independent quality control., Conclusions: We propose that there is sufficient evidence that is at least equivalent to that used to include GM-EIA and β-d-glucan testing, and that PCR is now mature enough for inclusion in the EORTC/MSG definitions., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)
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- 2015
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12. Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).
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Cornely OA, Gachot B, Akan H, Bassetti M, Uzun O, Kibbler C, Marchetti O, de Burghgraeve P, Ramadan S, Pylkkanen L, Ameye L, Paesmans M, and Donnelly JP
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- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents, Candida, Female, Fungemia microbiology, Fungemia mortality, Humans, Immunocompromised Host, Kaplan-Meier Estimate, Male, Middle Aged, Prospective Studies, Shock, Septic, Young Adult, Fungemia complications, Fungemia epidemiology, Leukemia complications, Leukemia epidemiology
- Abstract
Background: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies., Methods: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed., Results: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective., Conclusions: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2015
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13. Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.
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Herbrecht R, Patterson TF, Slavin MA, Marchetti O, Maertens J, Johnson EM, Schlamm HT, Donnelly JP, and Pappas PG
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- Adolescent, Adult, Aged, Child, Female, Humans, Male, Middle Aged, Prospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Invasive Pulmonary Aspergillosis drug therapy, Voriconazole therapeutic use
- Abstract
Background: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions., Methods: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged., Results: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA., Conclusions: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2015
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14. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.
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Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, and Cesaro S
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- Adolescent, Adult, Aged, Child, Child, Preschool, DNA, Viral blood, Epstein-Barr Virus Infections epidemiology, Epstein-Barr Virus Infections surgery, Epstein-Barr Virus Infections virology, Europe epidemiology, Herpesvirus 4, Human isolation & purification, Humans, Infant, Kaplan-Meier Estimate, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders surgery, Lymphoproliferative Disorders virology, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Rituximab, Viral Load, Antibodies, Monoclonal, Murine-Derived therapeutic use, Epstein-Barr Virus Infections drug therapy, Hematopoietic Stem Cell Transplantation, Immunologic Factors therapeutic use, Lymphoproliferative Disorders drug therapy
- Abstract
Background: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting., Methods: A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease., Results: One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival., Conclusions: More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.
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- 2013
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15. Galactomannan detection and diagnosis of invasive aspergillosis.
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Donnelly JP and Leeflang MM
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- Antigens, Fungal blood, Galactose analogs & derivatives, Humans, Invasive Pulmonary Aspergillosis blood, Mannans blood, Mycological Typing Techniques methods, Sensitivity and Specificity, Antigens, Fungal analysis, Bronchoalveolar Lavage Fluid chemistry, Invasive Pulmonary Aspergillosis diagnosis, Mannans analysis
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- 2010
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16. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients.
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Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T, Donnelly JP, Brown GD, Kullberg BJ, Blijlevens NM, and Netea MG
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- Adolescent, Adult, Aged, Antifungal Agents therapeutic use, Candidiasis drug therapy, Candidiasis immunology, Female, Fluconazole therapeutic use, Humans, Lectins, C-Type, Male, Middle Aged, Opportunistic Infections drug therapy, Opportunistic Infections immunology, Retrospective Studies, Young Adult, Candida growth & development, Candidiasis etiology, Hematopoietic Stem Cell Transplantation adverse effects, Immunocompromised Host genetics, Membrane Proteins genetics, Nerve Tissue Proteins genetics, Opportunistic Infections genetics, Polymorphism, Genetic
- Abstract
Background. Intensive treatment of hematological malignancies with hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence of opportunistic invasive fungal infection, but individual risk varies significantly. Dectin-1, a C-type lectin that recognizes 1,3-beta-glucans from fungal pathogens, including Candida species, is involved in the initiation of the immune response against fungi. Methods. Screening for the DECTIN-1 Y238X polymorphism within a group of 142 patients undergoing HSCT was correlated with Candida colonization and candidemia. Furthermore, functional studies were performed on the consequences of the polymorphism. Results. Patients bearing the Y238X polymorphism in the DECTIN-1 gene were more likely to be colonized with Candida species, compared with patients bearing wild-type DECTIN-1, necessitating more frequent use of fluconazole in the prevention of systemic Candida infection. Functional assays demonstrated a loss-of-function phenotype of the polymorphism, as shown by the decreased cytokine production by immune cells bearing this polymorphism. Conclusions. The Y238X polymorphism is associated with increased oral and gastrointestinal colonization with Candida species. This suggests a crucial role played by dectin-1 in the mucosal antifungal mechanisms in immunocompromised hosts. The finding that DECTIN-1 polymorphisms rendered HSCT recipients at increased risk for fungal complications may contribute to the selection of high-risk patients who should be considered for antifungal prophylaxis to prevent systemic candidiasis.
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- 2009
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17. Timely intervention for invasive fungal disease: should the road now lead to the laboratory instead of the pharmacy?
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de Pauw BE and Donnelly JP
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- Antifungal Agents administration & dosage, Fever physiopathology, Fungi isolation & purification, Humans, Antifungal Agents therapeutic use, Mycoses diagnosis, Mycoses drug therapy
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- 2009
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18. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.
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De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, and Bennett JE
- Subjects
- Humans, Mycoses classification, Mycoses diagnosis, Terminology as Topic
- Abstract
Background: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies., Methods: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved., Results: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only., Conclusions: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
- Published
- 2008
- Full Text
- View/download PDF
19. Halo sign and improved outcome.
- Author
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Verweij PE, van Die L, and Donnelly JP
- Subjects
- Aspergillosis diagnostic imaging, Aspergillosis pathology, Drug Administration Schedule, Humans, Lung diagnostic imaging, Lung Diseases, Fungal diagnostic imaging, Lung Diseases, Fungal pathology, Predictive Value of Tests, Antifungal Agents administration & dosage, Aspergillosis drug therapy, Lung pathology, Lung Diseases, Fungal drug therapy, Tomography, X-Ray Computed
- Published
- 2007
- Full Text
- View/download PDF
20. Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay.
- Author
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Maertens JA, Klont R, Masson C, Theunissen K, Meersseman W, Lagrou K, Heinen C, Crépin B, Van Eldere J, Tabouret M, Donnelly JP, and Verweij PE
- Subjects
- Adolescent, Adult, Aged, Aspergillosis blood, Aspergillosis microbiology, Female, Galactose analogs & derivatives, Humans, Immunoenzyme Techniques standards, Male, Mannans analysis, Middle Aged, Neutropenia immunology, Neutropenia microbiology, ROC Curve, Retrospective Studies, Sensitivity and Specificity, Aspergillosis diagnosis, Aspergillus isolation & purification, Immunoenzyme Techniques methods
- Abstract
Background: Many health care centers worldwide use the Platelia Aspergillus enzyme immunoassay (PA-EIA; Bio-Rad Laboratories) for diagnosis of invasive aspergillosis (IA). A cutoff optical density (OD) index of 1.5 was originally recommended by the manufacturer, but in practice, most institutions use lower cutoff values. Moreover, a cutoff OD index of 0.5 was recently approved in the United States. In the present study, we set out to optimize the cutoff level by performing a retrospective analysis of PA-EIA values for samples that had been obtained prospectively from adult patients at risk for IA at 2 European health care centers., Methods: In total, 239 treatment episodes were included of which there were 19 episodes of proven IA and 19 episodes of probable IA. Per-episode and per-test analyses and receiver operating characteristic curves were used to determine the optimal cutoff value., Results: In the per-episode analysis, lowering the cutoff OD index for positivity from 1.5 to 0.5 increased the overall sensitivity by 21% (from 76.3% to 97.4%) but decreased the overall specificity by 7% (from 97.5% to 90.5%). Requiring 2 consecutive samples with an OD index > or = 0.5 resulted in the highest test accuracy, with an improved positive predictive value. At a cutoff OD index of 0.5, the antigen test result was positive during the week before conventional diagnosis in 65% of cases and during the week of diagnosis in 79.5% of cases., Conclusions: A cutoff OD index of 0.5--identical to the approved cutoff in the United States--improves the overall performance of the PA-EIA for adult hematology patients.
- Published
- 2007
- Full Text
- View/download PDF
21. Clinical research in the lay press: irresponsible journalism raises a huge dose of doubt.
- Author
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Anaissie EJ, Segal BH, Graybill JR, Arndt C, Perfect JR, Kleinberg M, Pappas P, Benjamin D, Rubin R, Aberg JA, Adderson EE, Adler-Shohet FC, Akan H, Akova M, Almyroudis NG, Alexander BD, Andes D, Arrieta A, Baddley JW, Barron MA, Belzberg H, Boucher HW, Boyce TG, Casadevall A, Chandrasekar PH, Cleary JD, Cordonnier C, Cornely OA, Cuenca-Estrella M, Daly JS, Daoura N, Denning DW, dePauw B, de Repentigny L, Dignani MC, Dismukes WE, Donnelly JP, Donowitz GR, Dupont B, Drusano G, Ellis M, Espinel-Ingroff A, Fishman JA, Fleming R, Forrest G, Ghannoum M, Goldman M, Grazziutti M, Greene JN, Greenberg RN, Gubbins PO, Hadley S, Herbrecht R, Hiemenz JW, Hope W, Hospenthal DR, Husain S, Ito JI, Jacobson RM, Johnson M, Keating MR, Kett DH, Knapp K, Kontoyiannis DP, Krcmery VC, Larsen R, Laverdiere M, Ljungman P, Lortholary O, Maertens J, Marriott D, Mattiuzzi G, McGinnis MR, Morris M, Nucci M, Odds FC, Pankey GA, Patterson T, Pfaller M, Razonable RR, Reboli AC, Rinaldi MG, Roberts GD, Rodriguez Tudela JL, Rotstein C, Ruhnke M, Schuster M, Shoham S, Sia IG, Siebel N, Silviera F, Singh N, Sobel J, Solomkin JS, Sorrell TC, Steinbach WJ, Temesgen Z, Tortorano A, Vartivarian S, VerWeij P, Viscoli C, Viviani MA, Walker RC, Wheat JL, Wiley J, Williamson P, Wingard JR, Yu VL, and Zaoutis T
- Subjects
- Antifungal Agents administration & dosage, Antifungal Agents adverse effects, Caspofungin, Drug Approval methods, Echinocandins, Ethics Committees, Research ethics, Humans, Lipopeptides, Los Angeles, Multicenter Studies as Topic ethics, Multicenter Studies as Topic methods, Patient Selection, Peptides, Cyclic administration & dosage, Peptides, Cyclic adverse effects, Research standards, United States, Ethics, Research, Newspapers as Topic ethics, Professional Misconduct ethics
- Published
- 2006
- Full Text
- View/download PDF
22. Paradoxical increase in circulating Aspergillus antigen during treatment with caspofungin in a patient with pulmonary aspergillosis.
- Author
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Klont RR, Mennink-Kersten MA, Ruegebrink D, Rijs AJ, Blijlevens NM, Donnelly JP, and Verweij PE
- Subjects
- Adult, Aspergillosis immunology, Caspofungin, Echinocandins, Fungal Proteins therapeutic use, Hematopoietic Stem Cell Transplantation, Humans, Immunocompromised Host, Immunosuppressive Agents therapeutic use, Lipopeptides, Lung Diseases, Fungal immunology, Male, Myelodysplastic Syndromes therapy, Antifungal Agents therapeutic use, Antigens, Fungal blood, Aspergillosis drug therapy, Aspergillus fumigatus immunology, Lung Diseases, Fungal drug therapy, Peptides, Cyclic therapeutic use
- Abstract
A paradoxical increase in circulating Aspergillus antigen was observed during treatment with caspofungin in a patient with proven invasive aspergillosis. With the exception of treatment with the echinocandin, no other factors were found that might explain this clinical observation, which was supported by experiments done in vitro.
- Published
- 2006
- Full Text
- View/download PDF
23. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go.
- Author
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Donnelly JP
- Subjects
- Enzyme-Linked Immunosorbent Assay, Galactose analogs & derivatives, Humans, Mannans analysis, Mycology methods, Sensitivity and Specificity, Tomography, X-Ray Computed, beta-Glucans analysis, Aspergillosis diagnosis, Aspergillus isolation & purification, Blood microbiology, Polymerase Chain Reaction
- Published
- 2006
- Full Text
- View/download PDF
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