Rheology of the gel formed in the California Mastitis Test

The California Mastitis Test has previously been adapted for use in an inline, cow-side sensor and relies on the fact that the viscosity of the gel formed during the test is proportional to the somatic cell concentration. In this paper, the use of capillary and rotational viscometry was compared in light of the expected rheology of the gel formed during the test. It was found that the gel is non-Newtonian, but the initial phase of viscosity increase was not due to shear dependence, but rather due to the gelation reaction. The maximum apparent viscosity of the gel was shear dependent while the time it took to reach the maximum was not truly shear dependent, but was rather dependent on the degree of mixing during gelation. This was confirmed by introducing a delay time prior to viscosity measurement, in both capillary and rotational viscometry. It was found that by mixing the reagent and infected milk, then delaying viscosity measurement for 30 s, shortened the time it took to reach maximum viscosity by more than 60 s. The maximum apparent viscosity, however, was unaffected. It was found that capillary viscometry worked well to correlate relative viscosity with somatic cell count, but that it was sensitive to the reagent concentration. It can therefore be deduced that the rheology of the gel is complicated not only by it being non-Newtonian, but also by the strong dependence on test conditions. These make designing a successful sensor much more challenging

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in patients with non-Hodgkin's lymphoma in the United Kingdom (UK)

Introduction: We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors (G-CSFs) for prevention of febrile neutropenia (FN) following chemotherapy for non-Hodgkin’s lymphoma (NHL) in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of patients with NHL undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles); secondary prophylaxis (G-CSFs administered in all cycles following an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim; lenograstim and pegfilgrastim. Costs were taken from UK databases and utility values from published sources with the base case analysis using list prices for G-CSFs and a willingness to pay (WTP) threshold of £20,000 per QALY gained. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the base-case analysis the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 22%, secondary prophylaxis with pegfilgrastim for baseline FN risk 8-22%, and no G-CSFs for baseline FN risk less than 8%. Using a WTP threshold of £30,000, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 16%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusions: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on underlying FN risk level, patient age, and G-CSF price

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in patients with non-Hodgkin's lymphoma in the United Kingdom (UK)

Introduction: We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors (G-CSFs) for prevention of febrile neutropenia (FN) following chemotherapy for non-Hodgkin’s lymphoma (NHL) in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of patients with NHL undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles); secondary prophylaxis (G-CSFs administered in all cycles following an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim; lenograstim and pegfilgrastim. Costs were taken from UK databases and utility values from published sources with the base case analysis using list prices for G-CSFs and a willingness to pay (WTP) threshold of £20,000 per QALY gained. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the base-case analysis the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 22%, secondary prophylaxis with pegfilgrastim for baseline FN risk 8-22%, and no G-CSFs for baseline FN risk less than 8%. Using a WTP threshold of £30,000, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 16%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusions: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on underlying FN risk level, patient age, and G-CSF price

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis: systematic review and mixed method treatment comparison

Background This study assesses the efficacy of three granulocyte colony-stimulating factors (G-CSFs; pegfilgrastim, filgrastim and lenograstim) in preventing febrile neutropenia (FN). Methods A systematic review was undertaken. Head-to-head studies were combined using direct meta-analyses. In addition, an indirect Bayesian mixed treatment comparison (MTC) was undertaken to facilitate comparison between G-CSFs where there were no direct trials, and to allow data from all trials to be synthesised into a coherent set of results. Results The review identified the following studies comparing G-CSF prophylaxis to no primary G-CSF prophylaxis: 5 studies of pegfilgrastim, 9 studies of filgrastim and 5 studies of lenograstim. In addition, 5 studies were identified comparing pegfilgrastim to filgrastim. The two synthesis methods (meta-analysis and MTC) demonstrated that all three G-CSFs significantly reduced FN rate. Pegfilgrastim reduced FN rate to a greater extent than filgrastim (significantly in the head-to-head meta-analysis and in the MTC of all studies, and not quite significantly when the MTC was restricted to RCTs only). In the absence of direct trials, the MTC gave an 80-86% probability that pegfilgrastim is superior to lenograstim in preventing FN, and a 71-72% probability that lenograstim is superior to filgrastim. Conclusions Prophylaxis with G-CSFs significantly reduces FN rate. A head-to-head meta-analysis shows pegfilgrastim to be significantly superior to filgrastim in preventing FN events, while an MTC demonstrates that pegfilgrastim is likely to be superior to lenograstim

Consistency between direct trial evidence and Bayesian Mixed Treatment Comparison: Is head-to-head evidence always more reliable?

Objectives: This study aims to highlight the benefits of Bayesian mixed treatment comparison (MTC), within a case study of the efficacy of three treatments (pegfilgrastim, filgrastim and lenograstim) for the prevention of febrile neutropenia (FN) following chemotherapy. Methods: Two published meta-analyses have assessed the relative efficacy of the three treatments based on head-to-head trials. In the present study, all the trials from these meta-analyses were synthesised within a single network in a Bayesian MTC. Following a systematic review, the evidence base was then updated to include further recently-published trials. The metaanalyses and MTC were re-analysed using the updated evidence base. Results: Using data from the previously-published meta-analyses only, the relative risk of FN for pegfilgrastim vs. no treatment was estimated at 0.08 (95% confidence interval: 0.03, 0.18) from the head-to-head trial and 0.27 (95% credible interval: 0.12, 0.60) from the MTC, reflecting strong inconsistency between the results of the direct and indirect methodologies. When subsequently-published head-to-head trials were included, the meta-analysis estimate increased to 0.29 (95% confidence interval: 0.15, 0.55), while the MTC gave a relative risk of 0.34 (95% credible interval: 0.23, 0.54). The initial MTC results were therefore a better predictor of subsequent study results than was the direct trial. The MTC was also able to estimate the probability that there were clinically significant difference in efficacy between the treatments. Conclusions: Bayesian MTC provides clinically relevant information, including a measure of the consistency of direct and indirect evidence. Where inconsistency exists, it should not always be assumed that the direct evidence is more appropriate

Consistency between direct trial evidence and Bayesian Mixed Treatment Comparison: Is head-to-head evidence always more reliable?

Objectives This study aims to highlight the benefits of Bayesian mixed treatment comparison (MTC), within a case study of the efficacy of three treatments (pegfilgrastim, filgrastim and lenograstim) for the prevention of febrile neutropenia (FN) following chemotherapy. Methods Two published meta-analyses have assessed the relative efficacy of the three treatments based on head-to-head trials. In the present study, all the trials from these meta-analyses were synthesised within a single network in a Bayesian MTC. Following a systematic review, the evidence base was then updated to include further recently-published trials. The metaanalyses and MTC were re-analysed using the updated evidence base. Results Using data from the previously-published meta-analyses only, the relative risk of FN for pegfilgrastim vs. no treatment was estimated at 0.08 (95% confidence interval: 0.03, 0.18) from the head-to-head trial and 0.27 (95% credible interval: 0.12, 0.60) from the MTC, reflecting strong inconsistency between the results of the direct and indirect methodologies. When subsequently-published head-to-head trials were included, the meta-analysis estimate increased to 0.29 (95% confidence interval: 0.15, 0.55), while the MTC gave a relative risk of 0.34 (95% credible interval: 0.23, 0.54). The initial MTC results were therefore a better predictor of subsequent study results than was the direct trial. The MTC was also able to estimate the probability that there were clinically significant difference in efficacy between the treatments. Conclusions Bayesian MTC provides clinically relevant information, including a measure of the consistency of direct and indirect evidence. Where inconsistency exists, it should not always be assumed that the direct evidence is more appropriate

Granulocyte colony-stimulating factors for prevention of febrile neutropenia following chemotherapy: systematic review and meta-analysis

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in preventing FN in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 – 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 – 0.69) for filgrastim, and 0.62 (95% CI: 0.44 – 0.88) for lenograstim. Five studies compared pegfilgrastim with filgrastim; FN incidence was significantly lower for pegfilgrastim than filgrastim, with relative risk 0.66 (95% CI: 0.44 – 0.98). Conclusions: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in breast cancer in the United Kingdom

Introduction: We report a cost-effectiveness evaluation of granulocyte colony–stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) after chemotherapy in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of women with breast cancer undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles), secondary prophylaxis (G-CSFs administered in all cycles after an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim, lenograstim, and pegfilgrastim. Costs were taken from UK databases and utility values from published sources. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the UK, base-case analysis with a willingness-to-pay (WTP) threshold of £20,000 per quality-adjusted life-year gained and using list prices, the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 38%, secondary prophylaxis with pegfilgrastim for baseline FN risk 11% to 37%, and no G-CSFs for baseline FN risk less than 11%. Using a WTP threshold of £30,000 and list prices, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 29%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, earlier stage at diagnosis, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusion: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on the FN risk level for an individual patient, patient age and stage at diagnosis, and G-CSF price