scholarly journals A Survival Analysis of Invasive Fungal Diseases in Children with Cancer

2021 ◽  
Author(s):  
Letícia Maria Acioli Marques ◽  
Orlei Ribeiro de Araujo ◽  
Adriana Maria Paixão de Sousa da Silva ◽  
Dafne Cardoso Bourguignon da Silva ◽  
Fabianne Altruda de Moraes Costa Carlesse
Keyword(s):  
Failure Time ◽  
Hematologic Malignancies ◽  
Pulmonary Involvement ◽  
Fungal Diseases ◽  
Survival Times ◽  
Hematopoietic Stem ◽  
Survival Probabilities ◽  
Invasive Fungal Diseases ◽  
Hazard Ratios ◽  
Weibull Models

Abstract Objective The study aimed to determine the survival in a retrospective cohort of 152 patients treated for invasive fungal diseases (IFD) (133 proven and 19 probable) in 9 years. Methods The study included patients aged 0 to 18 years diagnosed with cancer at our institution and with proven or probable IFD, treated from 2011 to 2019. Weibull distribution was used for hazard ratios and accelerated failure time models for the outcome “death attributed to IFD.” Results The median age was 97 months. The most frequent diagnosis was leukemia (39, 25.7%). A total of 37 patients received prophylaxis with fluconazole (24.3%). Among 133 fungal isolates, the most frequent were Candida species in blood 81 (53.2%). Moreover, 43 deaths were attributed to IFD (28.3%). Survival probabilities were lower for pulmonary IFD (46.9%, p = 0.0017), leukemia (62.5%, p = 0.004), and neutropenia <500 cells/mm3 (55.4%, p < 0.0001). For Candida fungemia, survival probabilities were 76.6% (p = 0.043). In Weibull models, the diagnosis of leukemia shortened survival times by a factor of 0.006, relapse of disease by 0.05, lymphoma by 0.04, pulmonary IFD by 0.04, and neutropenia by 0.015. Hematopoietic stem cell transplantation did not affect the survival times as well as prophylaxis with fluconazole. Conclusion Host factors, such as neutropenia, relapse of disease, and hematologic malignancies, are determinants in the survival times of children with IFD as well as pulmonary involvement.

scholarly journals Attributable Hospital Cost and Antifungal Treatment of Invasive Fungal Diseases in High-Risk Hematology Patients: an Economic Modeling Approach

2011 ◽  
Vol 55 (5) ◽  
pp. 1953-1960 ◽  
Author(s):  
Michelle R. Ananda-Rajah ◽  
Allen Cheng ◽  
C. Orla Morrissey ◽  
Tim Spelman ◽  
Michael Dooley ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Case Control ◽  
Economic Modeling ◽  
Antifungal Drugs ◽  
Fungal Diseases ◽  
Antifungal Treatment ◽  
Hematopoietic Stem ◽  
Invasive Fungal Diseases ◽  
Defined Daily Doses ◽  
Matching Criteria

ABSTRACTStudies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT; liposomal amphotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs (n= 86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU$30,957 (95% confidence interval [CI] = AU$2,368 to AU$59,546;P= 0.034), approximating at purchasing power parity US$21,203 (95% CI = US$1,622 to US$40,784) and €15,788 (95% CI = €1,208 to €30,368), increasing to AU$80,291 (95% CI = AU$33,636 to AU$126,946;P= 0.001), i.e., US$54,993 (95% CI = US$23,038 to US$86,948) and €40,948 (95% CI = €17,154 to €64,742), with intensive care unit (ICU) requirement. Cost determinants were pharmacy costs (64%;P< 0.001) inclusive of antifungal treatment (27%;P< 0.001) and ward costs (27%;P= 0.091), with proportions persisting through 12 weeks for 25 surviving matched pairs (pharmacy, 60% [P= 0.12]; ward, 31% [P= 0.21]). Median LOS was not significantly increased unless unmatched patients were included (8 days, 95% CI = 1.8 to 14 days;P= 0.012). Excess C-ATs were 17 DDDs (95% CI = 15 to 19 DDDs;P< 0.001) per case patient and 19 DDDs (95% CI = 16 to 22 DDDs;P< 0.001) per ICU patient. The sensitivity analysis was confirmatory (for median cost, AU$29,441, 95% CI = AU$5,571 to AU$53,310,P= 0.016; for C-AT, 17 DDDs, 95% CI = 16 to 18 DDDs,P< 0.001). IFD results in increased hospital and ICU costs, with pharmacy costs, including antifungal treatment, being major determinants. Consumption of costly antifungal drugs may be a novel resource metric with wider generalizability than cost alone.

Predicting Difference in Mean Survival Time from Reported Hazard Ratios for Cancer Patients

2019 ◽  
Vol 39 (3) ◽  
pp. 228-238 ◽  
Author(s):  
Eeva-Liisa Røssell Johansen ◽  
Mette Lise Lousdal ◽  
Mette Vinther Skriver ◽  
Michael Væth ◽  
Ivar Sønbø Kristiansen ◽  
...  
Keyword(s):  
Survival Time ◽  
Cancer Patients ◽  
Empirical Relationship ◽  
Hazard Ratio ◽  
Cancer Type ◽  
Survival Times ◽  
Mean Survival Time ◽  
Hazard Ratios ◽  
Weibull Models

Background. Gain in mean survival time from new cancer treatments is a core component of cost-effectiveness analyses frequently used by payers for reimbursement decisions. Due to limited follow-up time, clinical trials rarely report this measure, whereas they often report hazard ratios comparing treatment groups. Aim. We aimed to explore the empirical relationship between gain in mean survival time and the hazard ratio for cancer patients. Methods. We included all patients in Norway diagnosed from 1965 through 2004 with late-stage cancer at the point of diagnosis and with one of the following cancers: stomach, colon, rectal, pancreas, lung and trachea, kidney excluding renal pelvis, and metastasized breast and prostate. Patients were followed until emigration, death, or June 30, 2016, whichever came first. Observed mean survival times and hazard ratios were obtained in subcohorts defined by patients’ sex, age, cancer type, and time period of diagnosis, which had nearly complete follow-up. Based on theoretical considerations, we fitted a linear relationship between observed differences in mean survival and logarithmic hazard ratios. For validation, we estimated differences in mean survival from hazard ratios of bootstrap samples with artificially induced censoring and compared with fitting a Weibull distribution. Results. The relationship between differences in mean survival time and corresponding logarithmic hazard ratios was linear for each of the included cancers. The predicted differences in mean survival of the empirical approach generally had smaller bias than the Weibull approach. Conclusion. For cancer diagnoses with poor prognosis, differences in mean survival times could be predicted from corresponding hazard ratios. This hazard ratio–based approach outperforms or is similar to fitting Weibull models to data with incomplete follow-up, while making fewer assumptions.

scholarly journals Isavuconazole for the treatment of patients with invasive fungal diseases involving the central nervous system

2019 ◽  
Vol 58 (4) ◽  
pp. 417-424 ◽  
Author(s):  
Stefan Schwartz ◽  
Oliver A Cornely ◽  
Kamal Hamed ◽  
Francisco M Marty ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Fungal Pathogens ◽  
Hematologic Malignancies ◽  
Fungal Diseases ◽  
Phase Iii ◽  
Clinical Activity ◽  
Invasive Fungal Diseases ◽  
Cryptococcus Species

Abstract The incidence of invasive fungal diseases (IFDs) with central nervous system (CNS) involvement is increasing due to the rising numbers of immunocompromised individuals, such as patients receiving chemotherapy, transplantation procedures, or immune-modulating therapies. CNS IFDs cause significant morbidity and mortality, and treatments are complicated by difficulties in identifying fungal pathogens and delivering antifungal agents to the CNS. Isavuconazole is a novel triazole with broad-spectrum activity that has shown good blood–brain barrier penetration in animal models. We present a retrospective analysis of isavuconazole in the treatment of patients with CNS IFDs and who either participated in the phase III VITAL or SECURE clinical trials, or were included in a named-patient program. A total of 36 patients were identified, including 27 patients from the clinical trials. Of these patients, 47.2% had hematologic malignancies, while 13.9% had no identifiable underlying conditions. Mucorales, Aspergillus species, and Cryptococcus species accounted for 30.6%, 22.2%, and 13.9% of infections, respectively. The overall survival rate was 80.6% at day 42 and 69.4% at day 84, and at the end of treatment, a complete or partial clinical response was achieved in 58.3% of patients. Isavuconazole exhibited clinical activity in a variety of CNS IFDs.

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