Antifungal prophylaxis during treatment for haematological malignancies: are we there yet?

Antifungal prophylaxis during treatment for haematological malignancies has been studied for 50 years, yet it has not been wholly effective even when using antifungal drugs that exhibit potent activity in vitro against a broad range of fungal pathogens. Trials have demonstrated that it can reduce the incidence of invasive fungal diseases (IFD) and fungal deaths, but only two studies have had an impact on overall mortality. Furthermore, it has not significantly reduced the need for empirical antifungal therapy.

Stenotrophomonas maltophilia: emerging disease patterns and challenges for treatment.

Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the classification and microbiology are outlined, together with clinical presentation, outcomes and management of infections due to S.

Effect of different impairment criteria on prevalence of “objective” mild cognitive impairment in a community sample.

Objectives: Objective cognitive impairment determined by neuropsychological test performance is a core criterion for the diagnosis of mild cognitive impairment (MCI), yet no consensus has been reached on how this criterion should be operationalized. The aims of this study were to investigate the effect of varying the criteria used to determine cognitive impairment (CI) on prevalence and case definition and to examine comparability of different criteria.

Design: Cross-sectional study.

Prevalence and predictors of “subjective cognitive complaints” in the Sydney Memory and Ageing Study.

Objectives: To document the prevalence of self- and informant report of cognitive problems, usually referred to as "subjective cognitive complaints" (SCCs), in a community-dwelling sample of older adults and to examine the relationship between SCCs and objective impairment, mood, and personality measures.

Participants: Eight hundred twenty-seven nondemented community-dwelling adults aged 70-90 years.

Measurements: Participants were asked 24 SCC questions, including the Memory Complaint Questionnaire (MAC-Q), and completed neuropsychological testing in the domains of memory, language, executive function, visuospatial skills, and psychomotor speed.

Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach.

Studies 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.

Clinically important detection of infection as an 'incidental' finding during cancer staging using FDG-PET/CT.

Background: FDG-PET/CT is widely used in the management of a variety of malignancies with excellent overall accuracy, despite the potential for false positive results related to infection and inflammation.

Aim:   As cancer patients can develop clinically inapparent infections, we evaluated the prevalence and nature of incidental findings reported to be suggestive of infections that had been identified during clinical cancer staging with FDG-PET/CT.

Methods: The study involved a retrospective analysis of 60 patients managed primarily at our facility from a total of 121 cases identified as having possible infection on clinical reporting of more than 4500 cancer staging investigations performed during the calendar year of 2008.

Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies.

Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy.

Discrete neuroanatomical networks are associated with specific cognitive abilities in old age.

There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions.

Antifungal prophylaxis in lung transplantation--a world-wide survey.

While variations in antifungal prophylaxis have been previously reported in lung transplant (LTx) recipients, recent clinical practice is unknown. Our aim was to determine current antifungal prophylactic practice in LTx centers world-wide. One nominated LTx clinician from each active center was invited by e-mail to participate in a web-based survey between September 2009 and January 2010.

The disease and economic burden of neutropenic fever in adult patients in Australian cancer treatment centres 2008: analysis of the Victorian Admitted Episodes Dataset.

Background: Although the incidence of neutropenic fever (FN) is estimated to be up to 80% for some malignancies, the epidemiological characteristics and economic burden are not well understood for Australian patients.

Aims: To describe underlying malignant conditions, potential aetiologies, clinical outcomes and healthcare utilization for an Australian population with FN, and to estimate the economic burden of this condition within the Australian healthcare sector.

Methods: Epidemiological features of FN were extracted from a population-based hospital morbidity dataset, the Victorian Admitted Episodes Dataset (VAED), for a 12-month period (2008).

An Australian survey of clinical practices in management of neutropenic fever in adult cancer patients 2009.

Background: An abundance of new evidence regarding treatment strategies for neutropenic fever is likely to contribute to variability in practice across institutions and clinicians alike.

Aims: To describe current clinical practices in Australia, by surveying haematologists, oncologists and infectious diseases physicians involved in cancer care.

Methods: Clinician members from Australian professional associations, accounting for the vast majority of Australian cancer specialists, were invited to participate in an electronic survey, comprising of a clinical case-based questionnaire.

Use of antibacterial prophylaxis for patients with neutropenia. Australian Consensus Guidelines 2011 Steering Committee.

The use of oral prophylactic antibiotics in patients with neutropenia is controversial and not recommended by this group because of a lack of evidence showing a reduction in mortality and concerns that such practice promotes antimicrobial resistance. Recent evidence has demonstrated non-significant but consistent, improvement in all-cause mortality when fluoroquinolones (FQs) are used as primary prophylaxis. However, the consensus was that this evidence was not strong enough to recommend prophylaxis.

Use of empiric antimicrobial therapy in neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee.

Administration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta-lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk.

Introduction to the Australian consensus guidelines for the management of neutropenic fever in adult cancer patients, 2010/2011. Australian Consensus Guidelines 2011 Steering Committee.

The current consensus guidelines were developed to standardize the clinical approach to the management of neutropenic fever in adult cancer patients throughout Australian treating centres. The three areas of clinical practice covered by the guidelines, the process for developing consensus opinion, and the system used to grade the evidence and relative strength of recommendations are described. The health economics implications of establishing clinical guidance are also discussed.

Endemic fungal infections in the Asia-Pacific region.

Endemic mycoses are important fungal infections in their respective habitats. In the Asia-Pacific region, an accurate epidemiological picture of endemic mycoses is elusive; few epidemiological surveys have been performed, and limited laboratory facilities and experience with fungal infections have further hampered recognition of infection. However, pockets of endemicity do indeed exist, and endemic fungal infections can have a significant impact on public health.

Functional alterations in brain activation and deactivation in mild cognitive impairment in response to a graded working memory challenge.

Aim: To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load.

Methods: In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for by individually calibrating the number of items presented at each load.

Echinocandin antifungal drugs in fungal infections: a comparison.

This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed echinocandins: caspofungin, micafungin and anidulafungin. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections. The echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including azole-resistant pathogens.

Pharmacoeconomics of voriconazole in the management of invasive fungal infections.

The incidence of invasive fungal infection has risen in recent years with the introduction of more intensive chemotherapy regimens and the advent of stem cell and solid-organ transplants. In patients undergoing chemotherapy, mortality rates ranging from 50 to 90% have been associated with documented invasive fungal infection. Voriconazole is a second-generation triazole, which is a synthesized derivative of fluconazole.

Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment.

The basal forebrain area (BFA) is closely connected to the hippocampus by virtue of cholinergic neuronal projections. Structural neuroimaging studies have shown reduced volumes of both structures in Alzheimer's disease and its prodromal stage mild cognitive impairment (MCI), but generally not in the same investigation. By combining voxel based morphometry and region of interest methods, we measured the grey matter (GM) volumes of the two brain regions with the goal of elucidating their contributions to MCI and its two subtypes (amnestic MCI and non-amnestic MCI) in an elderly epidemiological sample.

Chemical composition of five commercial Gynostemma pentaphyllum samples and their radical scavenging, antiproliferative, and anti-inflammatory properties.

Five Gynostemma pentaphyllum (GP) samples were investigated and compared for their chemical compositions and their antioxidant, antiproliferative, and anti-inflammatory effects. Extracts (50% acetone, 75% ethanol, and 100% ethanol) of the five GP samples (GP1-5) differed in their total phenolic, saponin, and flavonoid contents and in their rutin and quercetin concentrations. The highest level of total flavonoids was 63.

A multifactorial approach to understanding fall risk in older people.

Objective: To identify the interrelationships and discriminatory value of a broad range of objectively measured explanatory risk factors for falls.

Design: Prospective cohort study with 12-month follow-up period.

Setting: Community sample.

The relationship of neuropsychological function to instrumental activities of daily living in mild cognitive impairment.

Objective: While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between individuals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions.

Methods: The sample of 762 community-living participants aged 70-90 were assessed with a comprehensive neuropsychological test battery and with the informant-completed Bayer-Activities of Daily Living Scale (B-ADL).