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Choroid Plexus Tumours (CPTs) account for 1–4% of all brain tumours in children. Atypical choroid plexus papillomas (aCPPs) are a subset of these tumours, defined over a decade ago, yet no consensus exists on the optimal approach to their management. We conducted a retrospective analysis of all patients treated for CPTs at the Hospital for Sick Children between January 1, 2000, and December 31, 2018, and focused on patients with aCPP. Data extracted from the patient records for analysis included: demographic and clinical features, radiological imaging, surgical and adjuvant therapies, key pathological features, immunohistochemical staining for TP53 and tumour karyotype. Six of seven aCPP samples were profiled using Illumina HumanMethylationEPIC arrays and the top 10,000 most variably methylated probes were visualized using tSNE. Copy number inferencing was also performed. Twenty-nine patients were diagnosed with CPT, seven of whom had a diagnosis of aCPP as confirmed by histological review. Methylation profiling demonstrated that aCPPs clustered with both choroid plexus papillomas (CPPs) and choroid plexus carcinomas (CPCs). Complete resection of the tumour was pursued in all cases of aCPP and no patient received adjuvant therapy. All aCPP patients were alive at last follow up. This limited case series suggests that paediatric aCPP can be successfully managed with surgical resection alone, followed by a ‘watch and wait’ approach thus avoiding adjuvant therapies. A deeper understanding of the biology of aCPP is required to identify objective markers which can help provide robust risk stratification and inform treatment strategies.

Equitable access to essential medicines is a key facet of childhood cancer care, recognised by WHO as vital to improved childhood cancer outcomes globally. In the Caribbean, childhood cancer outcomes are poorer than those in most high-income countries. We aimed to generate in-depth comparative evidence of the current challenges and opportunities related to access to childhood cancer medicines in the Caribbean to identify context-sensitive health systems strategies to improve drug access and inform evidence-based paediatric cancer policies in the region.In this convergent, parallel, mixed-methods study, we mapped and analysed the determinants of access to childhood cancer medicines in four Caribbean countries (The Bahamas, Barbados, Jamaica, and Trinidad and Tobago). We analysed contextual determinants of access to medicines within and across study site jurisdictions, alignment of childhood cancer medicine inclusion between each country's national essential medicines list (NEML) and WHO's 2017 Essential Medicines List for Children, and availability and cost of chemotherapeutic agents at five tertiary care hospitals. We used a mixed-effects logistic regression model to analyse the association of medicine price, procurement efficiency (via median price ratio [MPR]), and site with drug availability. The fixed effect evaluated the effect of site and MPR on the probability of stockout in a given month. We assessed determinants of medicine access via thematic analysis of semi-structured qualitative interviews, literature, and policy documents.We collected and analysed data for 28 childhood cancer medicines from Barbados, 32 from The Bahamas, 30 from Trinidad and Tobago, and 31 from Jamaica. Despite stepwise inclusion of childhood cancer medicines in NEMLs, all four countries had frequent and recurrent stockouts for many cytotoxic medicines, showing no consistent relationship between NEML inclusion and availability. A mean MPR of greater than 3·0 in Trinidad and Tobago, The Bahamas, and Barbados suggests uniformly high procurement inefficiency, resulting in significant effects on drug stockout days. For each one unit increase in MPR the adjusted odds ratio (OR) of stockout increased by 10% (adjusted OR 1·10, 95% CI 1·04-1·16; p0·01). These challenges in access to childhood cancer medicines stem from health system and policy dynamics at institutional, national, and supranational levels that cause price volatility and erratic medicine availability. Key challenges include disparate policy commitments (eg, among sites), inefficient procurement and supply chain management practices, and local effects of international market pressures.The Caribbean region exemplifies deficiencies in access to childhood cancer medicines that might be overcome by improved regional harmonisation of drug registration, pharmacovigilance, and procurement alongside national forecasting to strengthen global pharmaceutical planning and prioritisation. Focused political attention to address these challenges is required to ensure efficient, reliable, and sustained availability of cancer mediciness.The SickKids-Caribbean Initiative.

BACKGROUND Embryonal rhabdomyosarcoma of the cervix is a rare and aggressive malignancy that usually affects children and young adults. CASE We describe a 2-year-old patient who presented with a mass protruding through the vaginal introitus. Preoperative investigations including vaginoscopy, hysteroscopy, magnetic resonance imaging, and biopsies confirmed embryonal rhabdomyosarcoma, botryoid subtype, arising from the cervix. She was successfully treated with neoadjuvant chemotherapy and interval laparoscopic radical trachelectomy to achieve remission. CONCLUSION Collaboration between the pediatric and adult surgical and medical oncology teams was critical to implement this fertility-sparing treatment strategy in such a young girl having this rare tumor.

Louis S Matza,1 Kristina S Boye,2 Jessica B Jordan,1 Kirsi Norrbacka,3 Raffaella Gentilella,4 Amara R Tiebout,1 Chantelle Browne,5 Marco Orsini Federici,4 Giovanni Biricolti,4 Katie D Stewart1 1Patient-Centered Research, Evidera, Bethesda, MD, USA; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Eli Lilly and Company, Helsinki, Finland; 4Eli Lilly and Company, Florence, Italy; 5Modeling and Simulation, Evidera, London, UK Objectives: Several glucagon-like peptide-1 receptor agonists are administered as weekly injections for treatment of type 2 diabetes (T2D). These medications vary in their injection processes, and a recent study in the UK found that these differences had an impact on patient preference and health state utilities. The purpose of this study was to replicate the UK study in Italy to examine preferences of an Italian patient sample, while allowing for comparison between utilities in the UK and Italy.Materials and methods: Participants with T2D in Italy valued health states in time trade-off interviews. All health states had the same description of T2D, but differed in description of the treatment process. As in the original UK study, the first health state described an oral treatment regimen, while additional health states added a weekly injection. The injection health states differed in three injection-related attributes: requirements for reconstituting the medication, waiting during medication preparation, and needle handling.Results: Interviews were completed by 238 patients (58.8% male; mean age = 60.2 years; 118 from Milan, 120 from Rome). The oral treatment health state had a mean (SD) utility of 0.90 (0.10). The injection health states had significantly (p < 0.0001) lower utilities, which ranged from 0.87 (requirements for reconstitution, waiting, and handling) to 0.89 (weekly injection with none of these requirements). Differences in health state utility scores suggest that each administration requirement was associated with a disutility (ie, negative utility difference): -0.006 (reconstitution), -0.006 (needle handling), -0.011 (reconstitution, needle handling), and -0.022 (reconstitution, waiting, needle handling).Conclusion: Disutilities associated with the injection device characteristics were similar to those reported with the UK sample. Results suggest that injection device attributes may be important to some patients with T2D, and it may be useful for clinicians to consider these attributes when choosing medication for patients initiating these weekly treatments. Keywords: utility, type 2 diabetes, injection process, GLP-1 receptor agonist, time trade-off, weekly injection, Italy, injection device&nbsp

Objectives: The primary aim of this study was to determine the prevalence of selected bacterial and viral enteropathogens in children hospitalized with acute gastroenteritis and the secondary aim was to characterize the clinical course and the outcome. Methodology: A retrospective audit of children (

Background: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. Methods: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. Results: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. Conclusions: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

Background Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs. Methods A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI. Results Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization. Conclusions A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552) Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1610-3) contains supplementary material, which is available to authorized users.

Background Prior analyses beyond clinical trials are yet to evaluate the projected lifetime benefit of apixaban treatment compared to low-molecular-weight heparin (LMWH)/vitamin K antagonist (VKA) for treatment of venous thromboembolism (VTE) and prevention of recurrences. The objective of this study is to assess the cost-effectiveness of initial plus extended treatment with apixaban versus LMWH/VKA for either initial treatment only or initial plus extended treatment. Methods A Markov cohort model was developed to evaluate the lifetime clinical and economic impact of treatment of VTE and prevention of recurrences with apixaban (starting at 10 mg BID for 1 week, then 5 mg BID for 6 months, then 2.5 mg BID for an additional 12 months) versus LMWH/VKA for 6 months and either no further treatment or extended treatment with VKA for an additional 12 months. Clinical event rates to inform the model were taken from the AMPLIFY and AMPLIFY-EXT trials and a network meta-analysis. Background mortality rates, costs, and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom National Health Service. The evaluated outcomes included the number of events avoided in a 1000-patient cohort, total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Results Initial plus extended treatment with apixaban was superior to both treatment durations of LMWH/VKA in reducing the number of bleeding events, and was superior to initial LMWH/VKA for 6 months followed by no therapy, in reducing VTE recurrences. Apixaban treatment was cost-effective compared to 6-month treatment with LMWH/VKA at an incremental cost-effectiveness ratio (ICER) of £6692 per QALY. When initial LMWH/VKA was followed by further VKA therapy for an additional 12 months (i.e., total treatment duration of 18 months), apixaban was cost-effective at an ICER of £8528 per QALY gained. Sensitivity analysis suggested these findings were robust over a wide range of inputs and scenarios for the model. Conclusions In the UK, initial plus extended treatment with apixaban for treatment of VTE and prevention of recurrences appears to be economical and a clinically effective alternative to LMWH/VKA, whether used for initial or initial plus extended treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12913-017-1995-8) contains supplementary material, which is available to authorized users.

Background. Patient-reported outcome measures are an important component of the evidence for health technology appraisal. Their incorporation into cost-effectiveness analyses (CEAs) requires conversion of descriptive information into utilities. This can be done by using bespoke utility algorithms. Otherwise, investigators will often estimate indirect utility models for the patient-reported outcome measures using off-the-shelf utility data such as the EQ-5D or SF-6D. Numerous modeling strategies are reported; however, to date, there has been limited utilization of Bayesian methods in this context. In this article, we examine the relative advantage of the Bayesian methods in relation to dealing with missing data, relaxing the assumption of equal variances and characterizing the uncertainty in the model predictions. Methods. Data from a large myeloma trial were used to examine the relationship between scores in each of the 19 domains of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 and the EQ-5D utility. Data from 1839 patients were divided 75%/25% between derivation and validation sets. A conventional ordinary least squares model assuming equal variance and a Bayesian model allowing unequal variance were estimated on complete cases. Two further models were estimated using conventional and Bayesian multiple imputation, respectively, using the full data set. Models were compared in terms of data fit, accuracy in model prediction, and characterization of uncertainty in model predictions. Conclusions. Mean EQ-5D utility weights can be estimated from the EORTC QLQ-C30/QLQ-MY20 for use in CEAs. Frequentist and Bayesian methods produced effectively identical models. However, the Bayesian models provide distributions describing the uncertainty surrounding the estimated utility values and are thus more suited informing analyses for probabilistic CEAs.

To assess the predictive validity of apixaban cost-effectiveness model by comparing key event rates from model to those seen in AMPLIFY and AMPLIFY-EXT trials in patients with venous thromboembolism (VTE). Markov model was developed to extrapolate the observed clinical impact of apixaban versus

The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK.A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews.Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation.This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

Background: Patient Reported Outcome Measures are an important component of the evidence for health technology appraisal. Their incorporation into cost effectiveness analyses (CEA) requires conversion of descriptive information into utilities. This can be done using bespoke utility algorithms. Otherwise, investigators will often estimate indirect utility models for the PROMS using off-the-shelf utility data such as the EQ-5D or SF-6D. Many different modeling strategies are reported in the literature; however, to date there has been limited utilization of Bayesian methods in this context. In this paper we use a large trial dataset containing the EORTC QLQ-C30 with MY20 and the EQ-5D to examine the relative advantage of the Bayesian methods in relation to dealing with missing data, relaxing the assumption of equal variances and characterizing the uncertainty in the model predictions. Methods: Data from a large myeloma trial were used to examine the relationship between scores in each of the 19 domains of the EORTC QLQ-C30/QLQ-MY20 and the EQ-5D utility. Data from 1839 patients was divided 75%/25% between derivation and validation sets. A conventional OLS model, assuming equal variance and a Bayesian model allowing unequal variance were estimated on complete cases. Two further models were estimated using conventional and Bayesian multiple imputation respectively, using the full dataset. Models were compared in terms of data fit, accuracy in model prediction and characterization of uncertainty in model predictions. Conclusions: Mean EQ-5D utility weights can be estimated from the EORTC QLQ-C30/QLQMY20 for use in CEA. Frequentist and Bayesian methods produced effectively identical models. However, the Bayesian models provide distributions describing the uncertainty surrounding the estimated utility values and are thus more suited informing analyses for probabilistic CEA.

Purpose To assess the cost-effectiveness of apixaban versus rivaroxaban, low-molecular-weight heparin (LMWH)/dabigatran, and LMWH/vitamin K antagonist (VKA) for the initial treatment and prevention of recurrent thromboembolic events in patients with venous thromboembolism (VTE). Methods A Markov model was developed to evaluate the pharmacoeconomic effect of 6 months of treatment with apixaban versus other anticoagulants over a lifetime horizon. Network meta-analyses were conducted using the results of the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy (AMPLIFY), EINSTEIN-pooled, and RE-COVER I and II trials for the following end points: recurrent VTE, major bleeds, clinically relevant non-major bleeds, and treatment discontinuations. The analysis was conducted from the perspective of the United Kingdom National Health Service. The outcomes evaluated were the number of events avoided in a 1000-patient cohort, total costs, life years, quality-adjusted life years (QALYs), and cost per QALY gained over a patient’s lifetime. Findings Treatment for 6 months with apixaban was projected to result in fewer recurrent VTE and bleeding events in comparison to rivaroxaban, LMWH/dabigatran, and LMWH/VKA. Apixaban was cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio of £2520 per QALY gained and was a dominant (ie, lower costs and higher QALYs) alternative to either rivaroxaban or LMWH/dabigatran. Sensitivity analysis indicated that results were robust over a wide range of inputs. Implications The assessment of the effects and costs of apixaban in this study predicted that apixaban is a dominant alternative to rivaroxaban and LMWH/dabigatran and a cost-effective alternative to LMWH/VKA for 6 months of treatment of VTE and the prevention of recurrence.

Background - There are now a variety of preference based health related quality of life measures available. These instruments describe health in different terms and also use different methods for measuring individual preferences for health. Whilst these instruments have been shown to have acceptable psychometric properties, they have also been shown to be affected by ceiling and/or floor effects. The presence of ceiling effects in the health descriptive system are of particular concern for health state preference modelling as it may impact upon the likelihood of observing censoring and/or compression. Where appropriate methodologies are available to deal with these problems, it is methodologically preferable to use them. In this paper we assess the impact of adopting Tobit models to deal with potential censoring in two datasets – the MVH EQ-5D data and the UK HUI2 health state preference data. In doing so, we will show the impact on estimated values and expected fit. Methods - For each dataset we estimate a generalised least squares model with random effects and a tobit random effects model. The specification of each utility function is equivalent to those in the original publications (Dolan 1997, McCabe et al 2005). For each model we report the estimated coefficients, the Mean Absolute Error (MAE), the Mean Square Error (MSE), the Root Mean Square Error (RMSE), the proportion of states where the absolute prediction error was greater than 0.1 and the correlation between observed and predicted values. Results - Censoring problems were found in the MVH EQ-5D data but not in the UK HUI2 data set. As expected the impact of adjusting for censoring is very different between the two datasets. Conclusion – The impact of taking account of potential censoring is much greater in the EQ-5D data than the HUI2 data. Although the EQ-5D 5 Level (EQ-5D 5L) will reduce the ceiling effect in the EQ-5D 3 Level (EQ-5D 3L), this will not provide a solution to the issue of censoring without a full re-estimation of utilities for all the health states it measures.

Objectives: To explore the impact of different utility measurement strategies on the results of a cost-effectiveness analysis, funding decisions, decision uncertainty and value of information. Methods: Data from a UK trial of two cancer therapies (active versus standard care) were analysed using NICE reference case methods. Within-trial, cost-utility analyses were conducted with utility based on a number of strategies: A) Observed EQ-5D; cancer-specific utility based on the EORTC QLQ-C30 B) the EORTC-8D and C) the QLQ_U; Mapping from QLQ-C30 to EQ-5D using an algorithm generated in D) the same cancer patient group and E) a different cancer group. Incremental cost-effectiveness ratios (ICERS) were calculated. Bootstrapped net benefit estimates allowed generation of cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was calculated using incremental cost scenarios. Results were compared across utility strategies. Results: There were small but important differences observed in the incremental QALYs which ranged from 0.067 (EQ-5D) to 0.036 (EORTC-8D). Large differences were observed in the ICERs generated; for strategies A to E these were: £57,513; £106,264; £102,785; £90,049; £78,885. Using an incremental cost scenario of £3,000 only strategy A yielded an ICER