Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?

The hydrolysis of sphingomyelin generates key molecules regulating cell growth and inducing apoptosis. Data from animal cancer models support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. In the intestinal tract, a sphingomyelinase with an optimum alkaline pH has been identified. We recently found that the activity of alkaline sphingomyelinase is significantly decreased in colorectal adenocarcinomas, indicating a potential anticarcinogenic role of this enzyme. To further examine whether the reduction of sphingomyelinase is present already in the premalignant state of neoplastic transformation, we measured sphingomyelinase activities in patients with familial adenomatous polyposis (FAP) and in sporadic colorectal tubulovillous adenomas. Tissue samples were taken from adenomas and surrounding macroscopically normal mucosa from 11 FAP patients operated with ileorectal anastomosis, from three FAP patients with intact colon, from 13 patients with sporadic colorectal adenomas and from 12 controls. Activities of acid, neutral and alkaline sphingomyelinase were measured together with alkaline phosphatase. In FAP adenoma tissue, alkaline sphingomyelinase activity was reduced by 90% compared to controls (P < 0.0001), acid sphingomyelinase by 66% (P < 0.01) and neutral sphingomyelinase by 54% (P < 0.05). Similar reductions were found in the surrounding mucosa. In sporadic adenoma tissue, only alkaline sphingomyelinase was reduced significantly, by 57% (P < 0.05). Alkaline phosphatase was not changed in FAP adenomas, but decreased in the sporadic adenomas. We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation. © 1999 Cancer Research Campaig

Data for: Hedging with Trees: Tail-Hedge Discounting of Long-Term Forestry Returns

Stumpage prices, Sweden 1909 - 2012, current prices and fixed prices (CPI deflated)

Value of a QALY and VSI estimated with the chained approach

The value of a quality-adjusted life-year (QALY) and the value of a statistical injury (VSI) are important measures within health economics and transport economics. Several studies have, therefore, estimated people's willingness to pay (WTP) for these estimates, but most results show scale insensitivity. The 'original' chained approach (CA) is a method developed to mitigate this problem by combining the contingent valuation (CV) with standard gamble (SG). In contrast to the version of the CA applied by the previous research of the WTP for a QALY, the original version allows the value of major health gains to be estimated without having the respondents express their WTP directly. The objective of this study was to estimate the value of a QALY and VSI in the context of non-fatal road traffic accidents using the original CA to test if the approach, applied to a wide range of health gains, is able to derive valid estimates and a constant value of a QALY which the previous research has not been able to show. Data were collected from a total of 800 individuals in the Swedish adult general population using two web-based questionnaires. The values of a QALY based on trimmed estimates were close to constant at €300,000 irrespective of the size of the QALY gain. The study shows that the original CA method may be a valid method to estimate the value of a QALY and VSI for major health losses. It also supports the use of a higher threshold value for a QALY than that which is currently applied by several health technology assessment agencies in different countries

Measuring the end-of-life premium in cancer using individual ex ante willingness to pay

For the assessment of value of new therapies in healthcare, Health Technology Assessment (HTA) agencies often review the cost per quality-adjusted life-year (QALY) gained. Some HTA agencies accept a higher cost per QALY gained when treatment is aimed at prolonging survival for patients with a short expected remaining lifetime, a so-called end-of-life (EoL) premium. The objective of this study is to elicit the existence and size of an EoL premium in cancer. Data was collected from 509 individuals in the Swedish general population 20–80 years old using a web-based questionnaire. Preferences were elicited using subjective risk estimation and the contingent valuation (CV) method. A split-sample design was applied to test for order bias. The mean value of a QALY was MSEK4.8 (€528,000), and there was an EoL premium of 4–10% at 6 months of expected remaining lifetime. Using subjective risk resulted in more robust and valid estimates of the value of a QALY. Order of scenarios did not have a significant impact on the WTP and the result showed scale sensitivity. Our result provides some support for the use of an EoL premium based on individual preferences when expected remaining lifetime is short and below 24 months. Furthermore, we find support for a value of a QALY that is above the current threshold of several HTA agencies