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

Codification challenges for data science in construction

New forms of data science, including machine learning and data analytics, are enabled by machine-readable informationbut are not widely deployed in construction. Aqualitative study of information flow in three projects usingBuilding Information Modelling (BIM) in the late designand construction phaseis used to identify the challenges of codification whichlimit the application of data science.Despite substantial efforts to codify information with ‘Common Data Environment(CDE)’ platforms to structure and transfer digital information within and between teams, participants work across multiple media in both structured and unstructured ways. Challenges of codification identified in this paper relate to software usage (interoperability, translation, modelling, and file-based sharing), information sharing (unstructured information, document control, workarounds, process change,and multiple CDEs), and construction process information(loss of constraints and low level of detail). This paper contributes to the current understanding of data science in construction by articulating the codification challenges and their implications for data quality dimensions,such as accuracy, completeness, accessibility, consistency, timeliness, and provenance.It concludes with practical implications for developingand using machine-readable information and directions for research to extract insight from data and support future automation

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

Association between superior semicircular canal dehiscence and other dehiscences in temporal bone

Background: The study of the association between superior semicircular canal and other dehiscences in the temporal bone. Materials and methods: We have studied computed tomography of radiologically diagnosed people with superior or posterior semicircular canal dehiscences, in four health centres. In addition, we have studied one isolated human temporal bone, one skull and one cadaver head belonging to the collection of the Department of Human Anatomy and Histology of the University of Zaragoza that had dehiscence in the superior semicircular canal. Results: The most frequent association that we observed was between superior semicircular canal dehiscence and tegmen tympani dehiscence (37.33%). Three cases (two clinical cases and one isolated temporal bone) showed multiple associated dehiscences (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal, glenoid cavity, tympanum bone and geniculate ganglion) associated with superior semicircular canal dehiscence Conclusions: When the superior semicircular canal dehiscence is associated to other in the petrous bone (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal) could be grouped into the same syndrome called "otic capsule syndrome", since they have the same origin and common aetiology (otic capsule)

Association between superior semicircular canal dehiscence and other dehiscences in temporal bone

Background: The study of the association between superior semicircular canal and other dehiscences in the temporal bone.Materials and methods: We have studied computed tomography of radiologically diagnosed people with superior or posterior semicircular canal dehiscences, in four health centres. In addition, we have studied one isolated human temporal bone, one skull and one cadaver head belonging to the collection of the Department of Human Anatomy and Histology of the University of Zaragoza that had dehiscence in the superior semicircular canal.Results: The most frequent association that we observed was between superior semicircular canal dehiscence and tegmen tympani dehiscence (37.33%). Three cases (two clinical cases and one isolated temporal bone) showed multiple associated dehiscences (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal, glenoid cavity, tympanum bone and geniculate ganglion) associated with superior semicircular canal dehiscence.Conclusions: When the superior semicircular canal dehiscence is associated to other in the petrous bone (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal) could be grouped into the same syndrome called “otic capsule syndrome”, since they have the same origin and common aetiology(otic capsule)

Numerical arc segmentation algorithm for a radio conference: A software tool for communication satellite systems planning

The Numerical Arc Segmentation Algorithm for a Radio Conference (NASARC) provides a method of generating predetermined arc segments for use in the development of an allotment planning procedure to be carried out at the 1988 World Administrative Radio Conference (WARC) on the Use of the Geostationary Satellite Orbit and the Planning of Space Services Utilizing It. Through careful selection of the predetermined arc (PDA) for each administration, flexibility can be increased in terms of choice of system technical characteristics and specific orbit location while reducing the need for coordination among administrations. The NASARC software determines pairwise compatibility between all possible service areas at discrete arc locations. NASARC then exhaustively enumerates groups of administrations whose satellites can be closely located in orbit, and finds the arc segment over which each such compatible group exists. From the set of all possible compatible groupings, groups and their associated arc segments are selected using a heuristic procedure such that a PDA is identified for each administration. Various aspects of the NASARC concept and how the software accomplishes specific features of allotment planning are discussed