Spontaneous Escherichia coli Meningitis and Pyogenic Ventriculitis in an Adult Receiving Anti-Tumour Necrosis Factor Alpha Therapy.

Presentation A 60-year-old male taking etanercept for ankylosing spondylitis was admitted to hospital with confusion and reduced level of consciousness over the preceding 24 hours. Diagnosis Magnetic Resonance Imaging (MRI) of his brain revealed pyogenic ventriculitis, and Escherichia coli was cultured from CSF. Treatment He required placement of an external ventricular drain and was treated with a prolonged course of intravenous ceftriaxone. Conclusion To our knowledge, this is the first reported case of spontaneous Gram-negative bacillary meningitis in a patient on anti-tumour necrosis factor (TNF)-alpha therapy, highlighting the risk of rare but serious infections associated with this class of medication.

Building a novel occupational rehabilitation program to support cancer survivors to return to health, wellness, and work in Australia.

PURPOSE: With a substantial increase in the population of cancer survivors of working age, issues concerning sustainable employment must be addressed. The health benefits of work are well established; however, the lack of support to transition back to work is a gap in survivorship care. Researchers, occupational rehabilitation and insurance sectors, cancer support services, and consumers have collaborated to develop a tailored, multimodal occupational rehabilitation program to support resumption of meaningful work for cancer survivors. This paper describes intervention development and refinement based on pilot results and expert- and consumer-recommendations. METHODS: The pilot was conducted within the life insurance sector, a collaboration fostered by global reinsurance company Swiss Re, with cancer survivors referred to an Australian provider of occupational rehabilitation services. RESULTS: Preliminary outcomes from 15 of 72 cancer survivors following adequate engagement (excluding those who withdrew or were still actively engaged) showed 10 (67%) with improved certified capacity to work, translating to 13 (87%) with improved work status. Consultant survey results indicated barriers to participation in and engagement with the program, including referral delays, health concerns, and cancer recurrence. Expert panel recommendations were used to refine the intervention and tailor to breast cancer survivors for the feasibility stage. CONCLUSIONS: Strengths include an innovative model of referral and funding, through a life insurance provider, the involvement of a multidisciplinary collaborative team to design, develop and implement the pilot, and considerable consumer involvement. IMPLICATIONS FOR CANCER SURVIVORS: The refined intervention will address a critical gap to improve reintegration into work and society, contributing to improved quality of life for cancer survivors in Australia. Models of referral through insurers to rehabilitation services could be adopted in other jurisdictions.

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFß antibody to promote durable rejection and immunity in squamous cell carcinomas.

BACKGROUND: Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFß signaling. METHODS: To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFß or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. RESULTS: We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFß monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFß, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFß antibody administration attenuates these effects. We show that α-TGFß acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFß acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. CONCLUSIONS: We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFß-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFß combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFß/α-PD-1 combination therapy (NCT02947165).

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Extended Lagrangian Excited State Molecular Dynamics.

An extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born-Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both for the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. The XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree-Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).

Effectiveness of Workplace Interventions in Return-to-Work for Musculoskeletal, Pain-Related and Mental Health Conditions: An Update of the Evidence and Messages for Practitioners.

Purpose The objective of this systematic review was to synthesize evidence on the effectiveness of workplace-based return-to-work (RTW) interventions and work disability management (DM) interventions that assist workers with musculoskeletal (MSK) and pain-related conditions and mental health (MH) conditions with RTW. Methods We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis that ranked evidence as strong, moderate, limited, or insufficient. Results Seven electronic databases were searched from January 1990 until April 2015, yielding 8898 non-duplicate references. Evidence from 36 medium and high quality studies were synthesized on 12 different intervention categories across three broad domains: health-focused, service coordination, and work modification interventions. There was strong evidence that duration away from work from both MSK or pain-related conditions and MH conditions were significantly reduced by multi-domain interventions encompassing at least two of the three domains. There was moderate evidence that these multi-domain interventions had a positive impact on cost outcomes. There was strong evidence that cognitive behavioural therapy interventions that do not also include workplace modifications or service coordination components are not effective in helping workers with MH conditions in RTW. Evidence for the effectiveness of other single-domain interventions was mixed, with some studies reporting positive effects and others reporting no effects on lost time and work functioning. Conclusions While there is substantial research literature focused on RTW, there are only a small number of quality workplace-based RTW intervention studies that involve workers with MSK or pain-related conditions and MH conditions. We recommend implementing multi-domain interventions (i.e. with healthcare provision, service coordination, and work accommodation components) to help reduce lost time for MSK or pain-related conditions and MH conditions. Practitioners should also consider implementing these programs to help improve work functioning and reduce costs associated with work disability.

Attentional Mechanisms in Autism, ADHD, and Autism-ADHD Using a Local-Global Paradigm.

OBJECTIVE: Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. METHOD: The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group ( N = 12 per group) on a set-shifting task, which included a local-global paradigm. RESULTS: Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). CONCLUSION: Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition.

Serious fungal infections in Canada.

There are currently no nationwide epidemiological data on fungal infections in Canada. We estimated the burden of serious fungal diseases using literature review and modeling, as per a methodology previously described by the LIFE program ( http://www.LIFE-worldwide.org ). Among the population of Canada (35.5 million in 2014), it was estimated that approximately 1.8% are affected by a serious fungal infection. Recurrent vulvovaginal candidiasis, severe asthma with fungal sensitization, and allergic bronchopulmonary aspergillosis are the most frequent infections, with population prevalences of 498,688 (1403/100,000), 73,344 (206/100,000), and 61,854 (174/100,000) cases, respectively. Over 3000 invasive fungal infections are estimated to occur annually, with incidences of 2068 cases (5.8/100,000) of invasive candidiasis, 566 cases (1.6/100,000) of invasive aspergillosis, 252 cases (0.71/100,000) of Pneumocystis pneumonia, 99 cases (0.28/100,000) of endemic mycoses, and 63 cases (0.18/100,000) of cryptococcosis. These estimates warrant validation through more formal epidemiological studies in Canada.

Inflammatory cues enhance TGFß activation by distinct subsets of human intestinal dendritic cells via integrin αvß8.

Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming growth factor-ß (TGFß), which is secreted by cells as a latent complex that requires activation to function. However, how TGFß activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFß, integrin αvß8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c+ but not the CD141+ intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFß-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvß8 expression and TGFß activation by human DC. We also show that DC expression of integrin αvß8 enhanced induction of FOXP3 in CD4+ T cells, suggesting functional importance of integrin αvß8 expression by human DC. These results show that microbial signals enhance the TGFß-activating ability of human DC via regulation of integrin αvß8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.

The effects of HIV disease and older age on laboratory-based, naturalistic, and self-perceived symptoms of prospective memory: does retrieval cue type and delay interval matter?

There is a rising prevalence of older HIV+ adults who are at risk of deficits in higher order neurocognitive functions and associated problems in everyday functioning. The current study applied multiprocess theory to examine the effects of HIV and aging on measures of laboratory-based, naturalistic, and self-perceived symptoms of prospective memory (PM). Participants included 125 Younger (48 with HIV, age = 32 ± 4.6 years) and 189 Older (112 with HIV, age = 56 ± 4.9 years) adults. Controlling for global neurocognitive functioning, mood, and other demographics, older age and HIV had independent effects on long-delay time-based PM in the laboratory, whereas on a naturalistic PM task older HIV- adults performed better than older HIV+ adults and younger persons. In line with the naturalistic findings, older age, but not HIV, was associated with a relative sparing of self-perceived PM failures in daily life across longer delay self-cued intervals. Findings suggest that, even in relatively younger aging cohorts, the effects of HIV and older age on PM can vary across PM delay intervals by the strategic demands of the retrieval cue type, are expressed differently in the laboratory and in daily life, and are independent of other higher order neurocognitive functions (e.g., retrospective memory).

Inhibiting Integrin αvß5 Reduces Ischemia-Reperfusion Injury in an Orthotopic Lung Transplant Model in Mice.

Primary graft dysfunction after lung transplantation is the leading cause of morbidity and mortality in the immediate posttransplant period and is characterized by endothelial and epithelial barrier disruption and the leakage of protein-rich edema fluid. Integrins are cell surface receptors that have an important role in maintenance of the cell barrier, and inhibition of integrins, such as αvß5, can diminish alveolar flooding in lung injury models. We hypothesized that inhibition of αvß5 during donor lung cold ischemia would reduce endothelial permeability during reperfusion. Using an orthotopic single lung transplantation model with and without cold ischemia, donor lungs were perfused with αvß5-blocking antibody (ALULA) or control antibody at the time of collection, followed by transplantation, 8 h of reperfusion, and the measurement of lung injury parameters. Prolonged cold ischemia (18 h) produced increases in extravascular lung water, protein permeability, and neutrophilic alveolitis and decreased oxygenation compared with lungs without cold ischemia. Perfusion of lungs with αvß5 antibody versus control antibody protected donor lungs from injury and significantly improved oxygenation. In summary, αvß5 integrin blockade protects from the development of ischemia-reperfusion lung injury and is a promising approach to preventing primary graft dysfunction in human lung transplant procedures.

Dynamical and transport properties of liquid gallium at high pressures.

Quantum molecular dynamics (QMD) simulations are used to calculate the equation of state, structure, and transport properties of liquid gallium along the principal shock Hugoniot. The calculated Hugoniot is in very good agreement with experimental data up to a pressure of 150 GPa as well as with our earlier classical molecular dynamics calculations using a modified embedded atom method (MEAM) potential. The self-diffusion and viscosity calculated using QMD agree with experimental measurements better than the MEAM results, which we attribute to capturing the complexity of the electronic structure at elevated temperatures. Calculations of the DC conductivity were performed around the Hugoniot. Above a density of 7.5 g/cm(3), the temperature increases rapidly along the Hugoniot, and the optical conductivity decreases, indicating simple liquid metal behavior.

Complex transition metal hydrides: linear correlation of countercation electronegativity versus T-D bond lengths.

For homoleptic 18-electron complex hydrides, an inverse linear correlation has been established between the T-deuterium bond length (T = Fe, Co, Ni) and the average electronegativity of the metal countercations. This relationship can be further employed towards aiding structural solutions and predicting physical properties of novel complex transition metal hydrides.

Knowledge to action for solving complex problems: insights from a review of nine international cases.

INTRODUCTION: Solving complex problems such as preventing chronic diseases introduces unique challenges for the creation and application of knowledge, or knowledge to action (KTA). KTA approaches that apply principles of systems thinking are thought to hold promise, but practical strategies for their application are not well understood. In this paper we report the results of a scan of systems approaches to KTA with a goal to identify how to optimize their implementation and impact. METHODS: A 5-person advisory group purposefully selected 9 initiatives to achieve diversity on issues addressed and organizational forms. Information on each case was gathered from documents and through telephone interviews with primary contacts within each organization. Following verification of case descriptions, an inductive analysis was conducted within and across cases. RESULTS: The cases revealed 5 guidelines for moving from conceiving KTA systems to implementing them: (1) establish and nurture relationships, (2) co-produce and curate knowledge, (3) create feedback loops, (4) frame as systems interventions rather than projects, and (5) consider variations across time and place. CONCLUSION: Results from the environmental scan are a modest start to translating systems concepts for KTA into practice. Use of the strategies revealed in the scan may improve KTA for solving complex public health problems. The strategies themselves will benefit from the development of a science that aims to understand adaptation and ongoing learning from policy and practice interventions, strengthens enduring relationships, and fills system gaps in addition to evidence gaps. Systems approaches to KTA will also benefit from robust evaluations.

TITRE: Passer de la connaissance à l'action pour résoudre des problèmes complexes : aperçu de l'examen de neuf cas internationaux. INTRODUCTION: La résolution de problèmes complexes du type de la prévention des maladies chroniques présente des défis particuliers pour la création et le transfert de connaissances, soit le passage de la connaissance à l'action (PCA). Les approches axées sur le PCA respectant les principes de la pensée systémique sont jugées prometteuses, mais les stratégies pour les mettre en place ne sont pas bien comprises. Dans cet article, nous présentons les résultats d'une analyse de plusieurs approches systémiques axées sur le PCA dans le but de déterminer comment optimiser leur mise en oeuvre et leur efficacité. MÉTHODOLOGIE: Un groupe consultatif de cinq personnes a choisi neuf initiatives représentant une diversité d'enjeux et de formes organisationnelles. Pour chaque cas, l'information a été recueillie à partir de documents et par l'entremise d'entrevues téléphoniques avec des personnes-ressources de chaque organisation. Après la vérification des descriptions de cas, une analyse inductive a été effectuée à la fois pour chaque cas et entre les cas. RÉSULTATS: Ces cas ont révélé cinq lignes directrices permettant de passer de la conception de systèmes de PCA à leur mise en oeuvre : 1) établir et entretenir des relations, 2) coproduire et organiser les connaissances, 3) créer des boucles de rétroaction, 4) les encadrer comme des interventions systémiques plutôt que comme des projets et 5) envisager des variations dans le temps et selon les lieux. CONCLUSION: Les résultats de cette analyse contextuelle constituent un départ modeste pour transformer en résultats concrets les concepts systémiques de PCA. L'utilisation des stratégies mises au jour pourrait améliorer le PCA pour la résolution de problèmes complexes en matière de santé publique. Les stratégies elles-mêmes pourront bénéficier de l'évolution d'une science visant à comprendre l'adaptation et l'apprentissage constant des politiques et des interventions pratiques, ce qui renforcera les relations durables et comblera les lacunes des systèmes, et pas simplement celles des données probantes. Les approches systémiques de PCA tireront également des bénéfices d'évaluations rigoureuses.

Invasive Saccharomyces cerevisiae in a liver transplant patient: case report and review of infection in transplant recipients.

Saccharomyces cerevisiae, an ascosporogenous yeast commonly used in the production of food, is an emerging infection in immunocompromised patients. We report the case of a 60-year-old man whose orthotopic liver transplant was complicated by S. cerevisiae fungemia and peritoneal abscess, successfully treated with caspofungin and drainage. We also review the literature of invasive saccharomycoses in recipients of hematologic and solid organ transplants.

ERCP cannulation success benchmarking: implications for certification and validation.

OBJECTIVE: Investigate success rates of cannulating a 'virgin' papilla during endoscopic retrograde cholangiopancreatography (ERCP) at a tertiary referral centre; determine reasons for failure and propose learnings for consideration in future revision of success benchmarking. DESIGN: Review of all ERCPs recorded on Endosoft database from 2006 to 2012 (n=1862). Specifically, 'virgin' papillae, defined as those with no evidence of prior surgical intervention, stents in situ or sphincterotomy (n=947). Virgin papillae present the most challenging target for endoscopists. SETTING: Gastroenterology department, St Thomas' Hospital, London. PATIENTS: All patients who underwent an ERCP recorded on Endosoft from 2006 to 2012 (n=1134). A proportion of these patients underwent repeat procedures, all considered virgin provided the aforementioned criteria were met. INTERVENTIONS: None, retrospective audit and benchmarking exercise. MAIN OUTCOME MEASURES: Determine criteria for successful cannulation of a virgin papilla. RESULTS: Overall success of cannulation of a virgin papilla at ERCP was 79.5%, 753 out of a total of 947 virgin papillae cases. Per patient with a virgin papilla, the success rate was 79.7%, 693 out of 869. Eliminating cases with features complicating cannulation increased success rates to 86% and 87%, respectively. Chronic pancreatitis was the single Indication associated with a failed cannulation (OR=3.9, CI 2.1 to 7.1), while biliary stones were significantly associated with a successful cannulation (OR=0.3, CI 0.2 to 0.4). Reasons for failure included patient agitation (OR=27.1, CI 7.9 to 92.7), duodenal stricturing (OR=12.5, CI 5.5 to 28.5), previous anatomy-changing surgery (OR=12.2, CI 3.3 to 45.4), tumour impingement (OR=9.5, CI 4.1 to 22.3) and equipment failure (OR=7.9, CI 1.4=43.5). CONCLUSIONS: The Joint Advisory Group's 80% success rate for completion of therapeutic intent must be viewed in light of published difficulty rating scales, if fair comparisons and standards are to be met. This highlights the need for standardised success criterion for ERCP training and accreditation.

Temperature measurements of shocked silica aerogel foam.

We present recent results of equation-of-state (EOS) measurements of shocked silica (SiO_{2}) aerogel foam at the OMEGA laser facility. Silica aerogel is an important low-density pressure standard used in many high energy density experiments, including the novel technique of shock and release. Due to its many applications, it has been a heavily studied material and has a well-known Hugoniot curve. This work then complements the velocity and pressure measurements with additional temperature data providing the full EOS information within the warm dense matter regime for the temperature interval of 1-15 eV and shock velocities between 10 and 40 km/s corresponding to shock pressures of 0.3-2 Mbar. The experimental results were compared with hydrodynamic simulations and EOS models. We found that the measured temperature was systematically lower than suggested by theoretical calculations. Simulations provide a possible explanation that the emission measured by optical pyrometry comes from a radiative precursor rather than from the shock front, which could have important implications for such measurements.

A plerixafor-based strategy allows adequate hematopoietic stem cell collection in poor mobilizers: results from the Canadian Special Access Program.

Plerixafor effectively mobilizes hematopoietic stem cells (HSCs). However, most patients' cells are successfully collected using traditional strategies and there is limited cost-effectiveness data. The objectives of this study were to: (1) summarize the published reports of mobilization using a plerixafor-based strategy during compassionate access programs and (2) describe the Canadian experience with plerixafor during its availability by Health Canada's Special Access Program. A literature search identified reports of plerixafor-based mobilization during compassionate access programs. Overall, successful collection of at least 2 × 10(6) CD34+ cells/kg was achieved in ~75% of patients, and about two-thirds of patients went on to HSCT. A greater proportion of patients had successful collections when plerixafor was used in the upfront or preemptive settings. Plerixafor was made available by Health Canada's SAP from September 2008 to December 2010. In 96 of 132 (73%) patients, there was successful collection of at least 2 × 10(6) CD34+ cells/kg. Ninety-nine (75%) patients went on to receive an autologous transplant. Plerixafor-based mobilization is effective in perceived poor mobilizers. The optimal way to incorporate plerixafor into a mobilization strategy, however, remains to be determined. Centre-specific analysis of resource utilization may help to identify the most cost-effective way to implement various plerixafor-based mobilization strategies.

Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.