Core Discrete Event Simulation Model for the Evaluation of Health Care Technologies in Major Depressive Disorder

ObjectiveA review of existing economic models in major depressive disorder (MDD) highlighted the need for models with longer time horizons that also account for heterogeneity in treatment pathways between patients. A core discrete event simulation model was developed to estimate health and cost outcomes associated with alternative treatment strategies.MethodsThis model simulated short- and long-term clinical events (partial response, remission, relapse, recovery, and recurrence), adverse events, and treatment changes (titration, switch, addition, and discontinuation) over up to 5 years. Several treatment pathways were defined on the basis of fictitious antidepressants with three levels of efficacy, tolerability, and price (low, medium, and high) from first line to third line. The model was populated with input data from the literature for the UK setting. Model outputs include time in different health states, quality-adjusted life-years (QALYs), and costs from National Health Service and societal perspectives. The codes are open source.ResultsPredicted costs and QALYs from this model are within the range of results from previous economic evaluations. The largest cost components from the payer perspective were physician visits and hospitalizations. Key parameters driving the predicted costs and QALYs were utility values, effectiveness, and frequency of physician visits. Differences in QALYs and costs between two strategies with different effectiveness increased approximately twofold when the time horizon increased from 1 to 5 years.ConclusionThe discrete event simulation model can provide a more comprehensive evaluation of different therapeutic options in MDD, compared with existing Markov models, and can be used to compare a wide range of health care technologies in various groups of patients with MDD.     

The influence of (public) health expenditure on longevity

Objectives

We report new evidence on the contribution of health expenditure to increasing life expectancy in OECD countries, differentiating the effects of public and private health expenditures.

Methods

A theoretical model is presented and estimated though a cross-country fixed effects multiple regression analysis for a sample of OECD countries over the period 1980–2000.

Results

Although the effect of aggregate health expenditure is not conclusive, public health expenditure plays a significant role in enhancing longevity. However, its influence diminishes as the size of the public health sector on GDP expands, reaching a maximum around the 8 %.

Conclusions

With the influence of public health expenditure being positive, the ambiguous effect of the aggregate expenditure suggests that the weight of public and private health sectors matters, the second having a lower impact on longevity. This might explain the poor evolution of the life expectancy in countries with a high amount of private resources devoted to health. In such cases, an extension of public services could give rise to a better outcome from the overall health investment.     

Estado actual y perspectivas futuras del trasplante de hepatocitos

The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT).Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results.Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment.     

Estado actual de la prevención y tratamiento de las complicaciones de los estomas. Revisión de conjunto

The aim of our study was to perform a review of the literature to assess the results of prevention and treatment of stoma complications.     

Inter-rater reliability of surgical reviews for AREN03B2: A COG renal tumor committee study

Purpose

The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews.

Methods

Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value).

Results

Local tumor stage correlated in all 3 reviews except in one case (Kappa = 0.9775, p < 0.001). Similarly, overall disease stage had excellent correlation (0.9422, p < 0.001). There was strong correlation for type of renal procedure (0.8357, p < 0.001), presence of tumor rupture (0.6858, p < 0.001), intraoperative tumor spill (0.6493, p < 0.001), and blood vessel involvement (0.6470, p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p < 0.001) and interpretation of residual disease status (0.5310, p < 0.001).

Conclusion

The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy.     

Prenatal retinoic acid increases lipofibroblast expression in hypoplastic rat lungs with experimental congenital diaphragmatic hernia

Background/purpose

Prenatal administration of all-trans retinoic acid (ATRA) has been shown to stimulate alveolarization in nitrofen-induced pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial lipofibroblasts (LIFs), characterized by adipocyte differentiation-related protein (ADRP), play a critical role in alveolar development by coordinating lipid homeostasis. Previous studies have demonstrated that ATRA positively affects LIF expression in developing lungs. We hypothesized that pulmonary LIF expression is increased after prenatal ATRA treatment in the nitrofen model of CDH-associated PH.

Methods

Timed-pregnant rats were treated with nitrofen or vehicle on E9.5, followed by injection of ATRA or placebo on E18.5, E19.5, and E20.5. Fetal lungs were dissected on E21.5 and divided into Control + Placebo, Control + ATRA, Nitrofen + Placebo, and Nitrofen + ATRA. Pulmonary gene expression levels of ADRP were analyzed by quantitative real-time polymerase chain reaction, and LIF expression was investigated by ADRP immunohistochemistry, oil-red-O-, and immunofluorescence-double-staining.

Results

Relative mRNA expression of pulmonary ADRP was significantly increased in Nitrofen + ATRA compared to Nitrofen + Placebo (0.31 ± 0.02 vs. 0.08 ± 0.01; P < 0.0001). ADRP immunoreactivity and oil-red-O-staining were markedly increased in alveolar interstitium of Nitrofen + ATRA compared to Nitrofen + Placebo. Immunofluorescence-double-staining confirmed markedly increased LIF expression in alveolar walls of Nitrofen + ATRA compared to Nitrofen + Placebo.

Conclusions

Increased LIF expression after prenatal treatment with ATRA in nitrofen-induced PH suggests that ATRA may have a therapeutic potential in attenuating CDH-associated PH by stimulating alveolar development.