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Invasive mycoses: strategies for effective management.

Effective management of invasive fungal infections (IFIs) depends on early individualized therapy that optimizes efficacy and safety. Considering the negative consequences of IFI, for some high-risk patients the potential benefits of prophylactic therapy may outweigh the risks.

When using a prophylactic, empiric, or preemptive therapeutic approach, clinicians must take into account the local epidemiology, spectrum of activity, pharmacokinetic and pharmacodynamic parameters, and safety profile of different antifungal agents, together with unique host-related factors that may affect antifungal efficacy or safety.

Therapeutic drug monitoring is increasingly recognized as important or necessary when employing lipophilic triazoles (itraconazole, voriconazole, posaconazole) or flucytosine. Because early diagnostics remain limited for uncommon, yet emerging opportunistic molds (e.g., Mucorales), and treatment delay is associated with increased mortality, early effective management often depends on a high index of suspicion, taking into account predisposing factors, host cues favoring mucormycosis, and local epidemiology.

Antifungal options for mucormycosis are limited, and optimal management depends on a multimodal approach that includes early diagnosis/clinical suspicion, correction of underlying predisposing factors, radical debridement of affected tissues, and extended antifungal therapy. This article discusses strategies for the effective management of invasive mycoses, with a particular focus on antifungal hepatotoxicity.

Delivery and Safety of Inhaled Interferon-γ in Idiopathic Pulmonary Fibrosis

Background: Inhaled interferon-γ aerosol (aINF-γ) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-γ (100 μg 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ).

Methods: IFN-γ activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12–14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-γ.

Results: All 10 patients tolerated 80 weeks of inhaled IFN-γ well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7±4.81% (±SEM). In vivo lung deposition averaged 65.4±4.8μg and oropharyngeal deposition 12.6±3.0 μg. BAL IFN-γ increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-γ plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged.

Conclusions: IFN-γ is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma

Perrin K, Wijesinghe M, Healy B, Wadsworth K, Bowditch R, Bibby S, Baker T, Weatherall M, Beasley R (Source: The Aspergillus Website - articles)

Factors Affecting Efficacy and Safety of Add-On Combination Chemotherapy for Non-Small-Cell Lung Cancer: A Literature-Based Pooled Analysis of Randomized Controlled Trials

Conclusions  The present results indicate that the following points are important when investigating new regimen for add-on combination chemotherapy: (1) the number of total combination drugs should be reduced if at all possible; (2) an add-on drug should be noncytotoxic and should not necessitate dose modification (reduction) of the base drug(s). Content Type Journal ArticlePages 1-10DOI 10.1007/s00408-012-9379-7Authors Kouichi Inoue, Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641 JapanMamoru Narukawa, Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, Shirokane 5-9-1, Minato-k...

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Effects of Extra-Fine Inhaled and Oral Corticosteroids on Alveolar Nitric Oxide in COPD

Conclusions  Whilst CANO remains a biomarker of interest in COPD, it is not suppressed by systemic or extra-fine particle ICS. CANO is not a useful marker for monitoring response of small airway disease to therapies in COPD. The study was approved by the local Committee on Medical Research Ethics and registered on ClinicalTrials.Gov (NCT 00921921). Content Type Journal ArticlePages 1-7DOI 10.1007/s00408-012-9378-8Authors Philip M. Short, Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Dundee, DD1 9SY ScotlandPeter A. Williamson, Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Dundee, DD1 9SY ScotlandBrian...

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