Cost-consequence analysis of remifentanil-based analgo-sedation vs. conventional analgesia and sedation for patients on mechanical ventilation in the Netherlands

Introduction: Hospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach. Methods: A Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of 2-3 days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours. Results: The average total 28-day costs were 15,626 euros with RS versus 17,100 euros with CS, meaning a difference in costs of 1474 euros (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis. Conclusions: Compared to CS, RS significantly decreases the overall costs in the ICU

Genetic Predisposition to Gastric Cancer: CDH1 and Beyond

Gastric cancer is a complex disease influenced by strong genetic and environmental factors. Hereditary gastric cancer syndromes are thought to account for between 1-3% of all cases. The most common hereditary gastric cancer syndrome is Hereditary Diffuse Gastric Cancer (HDGC), an autosomal dominant cancer syndrome that is primarily characterised by an extreme risk of developing diffuse-type gastric cancer. Approximately 40% of families that fit the clinical criteria for HDGC carry a pathogenic variant in germline CDH1. An explanation for the remaining 60% of cases remains largely elusive. While New Zealand as a whole is a country with a low-incidence of gastric cancer, Māori have an age-standardised incidence of gastric cancer more than three times that of non-Māori. Additionally, Māori have an average age of diagnosis approximately 10 years younger than non-Māori, and are one of the few populations worldwide with a higher incidence of the diffuse-type disease. To assess the contribution of HDGC to the high-incidence of diffuse gastric cancer for Māori, we analysed the CDH1 sequence from an unselected cohort of 94 Māori gastric cancer patients and 200 healthy matched controls using next-generation amplicon sequencing, multiplex ligation-dependent probe amplification, and Sanger sequencing. Pathogenic CDH1 variants were identified in 18% of all cases, 34% of diffuse gastric cancers, and 66% of early-onset cases (< 45 years of age). After adjusting for the effect of clinical genetic testing for known Māori HDGC families, we estimate 6% of all Māori gastric cancer patients and 13% of diffuse gastric cancer patients carry pathogenic germline CDH1 variants. Chile is a country with a high-incidence of gastric cancer and no formal genetic screening programme for gastric cancer patients. To explore pathogenic germline CDH1 variants as a cause of gastric cancer in Chile, next-generation amplicon sequencing and Sanger sequencing were used to screen a cohort of 51 Chilean gastric cancer patients that presented with a striking family history or early-onset disease. Overall, one clear pathogenic CDH1 variant was identified, representing 2.0% of all probands and 3.6% of probands who met the clinical criteria for HDGC. Although pathogenic CDH1 variants were rare in this Chilean cohort, we were able to screen the extended family of the one proband with a confirmed mutation and identify five further carriers. These carriers will now benefit from surveillance and early intervention. Finally, whole-exome sequencing was used to examine 14 diffuse gastric cancer patients that fit the clinical criteria for HDGC and did not carry a pathogenic variant in their germline CDH1. Variants in these patients were filtered and prioritised for further evaluation and validation using Sanger sequencing. Single probands were found to carry pathogenic variants in ATM and TP53, genes which are not associated with HDGC, but are known to increase gastric cancer risk. Additional mutations of interest were identified in FARP2, FGD4, and LMO7, genes that are important in the coordination of the actin cytoskeleton and/or cell adhesion, pathways which are dysregulated in diffuse-type gastric tumours. Until now, FARP2, FGD4, and LMO7 were not linked with diffuse gastric cancer risk. It is clear from the current study and other HDGC studies, that there is no other common gene for HDGC, however families may carry private variants in genes rarely associated with disease. Taken together, these studies demonstrate the variable frequency of pathogenic variants in germline CDH1 in different populations, the absence of other commonly mutated genes in familial diffuse gastric cancers, and the importance of genetic screening and targeted interventions for those that carry pathogenic variants

Multiplier Effects and Compensation Mechanisms for Inclusion in Health Economic Evaluation:A Systematic Review

Background: Compensation mechanisms and multiplier effects may affect productivity losses due to illness, disability, or premature death of individuals. Hence, they are important in estimating productivity losses and productivity costs in the context of economic evaluations of health interventions. This paper presents a systematic literature review of papers focusing on compensation mechanisms and multiplier effects, as well as whether and how they are included in health economic evaluations. Methods: The systematic literature search was performed covering EconLit and PubMed. A data-extraction form was developed focusing on compensation mechanisms and multiplier effects. Results: A total of 26 studies were included. Of these, 15 were empirical studies, three studies were methodological studies, two studies combined methodological research with empirical research, four were critical reviews, one study was a critical review combined with methodological research, and one study was a cost–benefit analysis. No uniform definition of compensation mechanisms and multiplier effects was identified. The terminology used to describe compensation mechanisms and multiplier effects varied as well. While the included studies suggest that both multipliers as well as compensation mechanisms substantially impact productivity cost estimates, the available evidence is scarce. Moreover, the generalizability as well as validity of assumptions underlying the calculations are unclear. Available measurement methods for compensation mechanisms and multiplier effects differ in approaches and are hardly validated. Conclusion: While our review suggests that compensation mechanisms and multiplier effects may have a significant impact on productivity losses and costs, much remains unclear about their features, valid measurement, and correct valuation. This hampers their current inclusion in economic evaluation, and therefore, more research into both phenomena remains warranted.</p

Development of the Treatment Inventory of Costs in Psychiatric Patients: TIC-P Mini and Midi

AbstractBackgroundMedical costs of (psychiatric) illness can be validly measured with patient report questionnaires. These questionnaires comprise many detailed items resulting in lengthy administrations.ObjectivesWe set out to find the minimal number of items needed to retrieve 80% and 90% of the costs as measured by the Treatment Inventory of Costs in Patients with psychiatric disorders (TIC-P).MethodsThe TIC-P is a validated patient-reported outcome measure concerning the utilization of medical care and productivity losses. The present study focused on direct medical costs. We applied data of 7756 TIC-P administrations from three studies in patients with mental health care issues. Items that contribute least to the total cost were eliminated, providing that 80% and 90% of the total cost was retained.ResultsAverage medical costs per patient were €658 over the last 4 weeks. The distribution of cost was highly skewed, and 5 of the 14 items of the TIC-P accounted for less than 10% of the total costs. The 80% Mini version of the TIC-P required five items: ambulatory services, private practice, day care, general hospital, and psychiatric clinic. The TIC-P Midi 90% inventory required eight items. Both had variance between the three samples in the optimal choice of the items.ConclusionsThe number of items of the TIC-P can be reduced considerably while maintaining 80% and 90% of the medical costs estimated by the complete TIC-P. The reduced length makes the questionnaire more suitable for routine outcome monitoring

A Systematic Review of Literatures onFactors Associated with Educational ndAcademic Performance in Attention DeficitHyperactivity Disorder

__Abstract__ Attention Deficit Hyperactivity Disorder (ADHD) has been shown to impair major life activities including educational functioning. However, there is no consensus on the specific cause for the impact on this worse educational outcome. This systematic review aims to identify factors that have been associated with educational and academic underperformance of children and adolescents with ADHD. A literature search was conducted using PubMed and the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The study focused on articles presenting results of data-based analyses related to ADHD and keywords related to education. The search resulted in 376 records that were screened by title. Of these, 185 articles were screened by abstract and 35 met the eligibility criteria for inclusion in the review. These 35 articles were related to seven domains: educational training, educational environment, pharmacological treatment, ADHD symptoms, associations of ADHD with academic outcomes, self-concept, and specific skills. The main source of educational challenges seems to be related to the inattentive symptoms (or subtype) of ADHD. This outcome is different than expected, since hyperactive symptoms are pronounced more prominently and often refer children to clinical practice. Inattentive symptoms amongst others refer to difficulties in organization skills and can lead to decreased self-efficacy and development of depressive symptoms. This decreased self-efficacy and the depressive symptoms were also found to be related to influence the relation between ADHD and academic performance. Educational outcomes were shown to be improved using small group work, learning via a computer-based service and as a result of coaching and pharmacological treatment. To help children and adults achieve educational goals that now are out of reach, more attention should be spent to the inattentive symptoms of ADHD and possibilities to overcome experienced problems