BackgroundAntifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.MethodsRandomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.ResultsFive eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35–0.76), posaconazole (OR: 0.56; IQR: 0.32–0.99), and voriconazole (OR: 0.46; IQR: 0.28–0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17–0.58) and voriconazole (OR: 0.33; IQR: 0.17–0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42–1.12). All-cause mortality was similar across all mould-active agents.ConclusionAs expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0855-6) contains supplementary material, which is available to authorized users.

This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%), gastrointestinal AEs (3.2–66.7%), and amenorrhea and/or ovarian complications (0–71%). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp.) or AZA (17–77% versus 11–29%, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp.) or AZA (32–71% versus 8–18%, resp.). Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

Summary

In specific clinical settings, FISH could be cost effective for melanoma diagnosis.

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