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Objectives

Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known.

Design

A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events.

Results

Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5–20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates.

Conclusions

Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics.  相似文献   
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This review presents the first detailed presentation of the parallelism between the Tuskegee Syphilis Study and the Captain America graphic novel ‘TRUTH: Red, White and Black’, published as a graphic novel by Marvel Comics in 2004 as a paperback, and then in 2009 as a hardcover. First written, published and distributed monthly in 2003 as pre-sequel seven comic book series to tell the story of the origins of the WWII superhero Captain America. In 2003, Marvel Comics chose to tell a ‘very dark story’ to explain the origins of Captain America, a half century after the initial introduction of Captain America as a WWII action hero in 1940. By detailing—for the first time—nine parallel aspects between these two storylines, this review demonstrates how Marvel Comics brought the tragic Tuskegee Syphilis Study story into the popular press, thus reaching an audience far beyond traditional bioethics academicians. This review is intended to stimulate and guide classroom discussions on the ethical issues at the core of the infamous Tuskegee Syphilis Study allowing bioethical issues to be made more accessible to the general public, via school curriculums, by the use of graphic novels.  相似文献   
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Purpose

Potential roles of inherited and environmental risk factors in pathogenesis of Langerhans cell histiocytosis (LCH), a myeloid neoplastic disorder, are undefined. We therefore evaluated the role of parental and perinatal factors on the risk of this childhood cancer.

Methods

Information on LCH cases (n = 162) for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated included parental age, race/ethnicity, size for gestational age, and birth order. Logistic regression was used to generate an adjusted odds ratio (aOR) and 95% confidence interval (CI) testing the association between each factor and LCH.

Results

Few perinatal or parental factors were associated with LCH risk, with the exception of race/ethnicity. Mothers of Hispanic ethnicity were more likely to have children who developed LCH compared to non-Hispanic whites (aOR: 1.51; 95% CI: 1.02–2.25). This risk increased when both parents were Hispanic (aOR: 1.80; 95% CI: 1.13–2.87). Non-Hispanic black mothers were suggested as less likely to give birth to offspring who developed LCH compared to non-Hispanic whites (aOR: 0.50; 95% CI: 0.24–1.02).

Conclusions

LCH is characterized by somatic mutations in MAPK pathway genes in myeloid precursors. Increased risk for LCH in children of Hispanic parents suggests potential impact of inherited factors on LCH pathogenesis.  相似文献   
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