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Objectives: To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management of periprosthetic joint infections (PJIs).Methods: Using the dissolvable bead biofilm assay, the minimum biofilm eradication concentration (MBEC) was determined for the most commonly used antimicrobial agents and combination regimens against staphylococcal PJIs. The established fractional inhibitory concentration (FIC) index was modified to create the fractional biofilm eradication concentration (FBEC) index to evaluate synergism or antagonism between antibiotics.Results: Only gentamicin (MBEC 64 mg/L) and daptomycin (MBEC 64 mg/L) were observed to be effective antistaphylococcal agents at clinically achievable concentrations. Supplementation of gentamicin with daptomycin, vancomycin or ciprofloxacin resulted in a similar or lower MBEC than gentamicin alone (FBEC index 0.25-2). Conversely, when rifampicin, clindamycin or linezolid was added to gentamicin, there was an increase in the MBEC of gentamicin relative to its use as a monotherapy (FBEC index 8-32).Conclusions: This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms. [ABSTRACT FROM AUTHOR]

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning. [ABSTRACT FROM PUBLISHER]

We studied 123 patients with malignant peripheral nerve sheath tumours (MPNSTs) between 1979 and 2002. However, 90 occurred sporadically whereas 33 were associated with neurofibromatosis type 1 (NF1). Survival was calculated using Kaplan-Meier survival curves and we used Cox's proportional hazards model to identify independent prognostic factors. A 5-year survival for 110 nonmetastatic patients was 54%; (33% NF1 and 63% sporadic P = .015). Tumour stage and site were significant prognostic indicators after univariate analysis. After multivariate analysis, however, only NF1 (P = .007) and tumour volume more than 200m (P = .015) remained independent predictors of poor outcome. We recommend that NF1 be taken into account during MPNST staging. As the survival rate in the NF group was dependant on tumour volume, routine screening of these patients with FDG PET and/or MRI may be warranted, thereby staging and controlling them at the earliest possible opportunity. [ABSTRACT FROM AUTHOR]

We studied 123 patients with malignant peripheral nerve sheath tumours (MPNSTs) between 1979 and 2002. However, 90 occurred sporadically whereas 33 were associated with neurofibromatosis type 1 (NF1). Survival was calculated using Kaplan-Meier survival curves and we used Cox’s proportional hazards model to identify independent prognostic factors. A 5-year survival for 110 nonmetastatic patients was 54%; (33% NF1 and 63% sporadic P = .015). Tumour stage and site were significant prognostic indicators after univariate analysis. After multivariate analysis, however, only NF1 (P = .007) and tumour volume more than 200m (P = .015) remained independent predictors of poor outcome. We recommend that NF1 be taken into account during MPNST staging. As the survival rate in the NF group was dependant on tumour volume, routine screening of these patients with FDG PET and/or MRI may be warranted, thereby staging and controlling them at the earliest possible opportunity. [ABSTRACT FROM AUTHOR]

More tourists are visiting the idyllic waters of the South Pacific each year. They share the shallow waters with the native wildlife, including the venomous stonefish. Although the injection of its venom has been reported to have occasional fatal neuromuscular and cardiovascular sequelae, severe tissue necrosis at the injection site has not been described. We present a case of stonefish injury that describes serious localised sequelae of stonefish envenomation [ABSTRACT FROM AUTHOR]

More tourists are visiting the idyllic waters of the South Pacific each year. They share the shallow waters with the native wildlife, including the venomous stonefish. Although the injection of its venom has been reported to have occasional fatal neuromuscular and cardiovascular sequele, severe tissue necrosis at the injection site has not been described. We present a case of stonefish injury that describes serious localised sequele of stonefish envenomation [ABSTRACT FROM AUTHOR]