The Effectiveness of Health Screening.

Using a matched insurant-general practitioner panel data set, we estimate the effect of a general health-screening program on individuals' health status and health-care cost. To account for selection into treatment, we use regional variation in the intensity of exposure to supply-determined screening recommendations as an instrumental variable. We find that screening participation increases inpatient and outpatient health-care costs up to 2 years after treatment substantially. In the medium run, we find cost savings in the outpatient sector, whereas in the long run, no statistically significant effects of screening on either health-care cost component can be discerned. In sum, screening participation increases health-care cost. Given that we do not find any statistically significant effect of screening participation on insurants' health status (at any point in time), we do not recommend a general health-screening program. However, given that we find some evidence for cost-saving potential for the sub-sample of younger insurants, we suggest more targeted screening programs.

Demand and supply of emergency help: an economic analysis of Red Cross services.

This paper analyzes supply and demand side characteristics of (voluntary) Red Cross services in Austria. The demand side analysis is based on a contingent valuation study on people's willingness to pay for emergency treatment, transportation services and disaster relief activities. The supply side is identified by a high percentage of volunteers in the Red Cross organization which makes the provision of emergency help at low cost possible. We find that aggregate benefits of Red Cross services exceed their cost of production. Policy conclusions are drawn with respect to future recruitment and funding: whereas intrinsic motivation is important for the decision to volunteer, and financial incentives play a minor role in general, the young Red Cross activists work voluntarily for self-realization reasons and to continue their education. Age-specific recruitment strategies accompanied by word-of-mouth advertising are recommended to address potential volunteers. As long as the volunteering character of Red Cross services will be maintained and cost of production will not go up an increase of funds does not seem necessary in the future. Moreover, a radical change in the structure of funding may crowd out both donations and voluntary labor supply.

Old boys' network in general practitioners' referral behavior?

We analyzed the impact of social networks on general practitioners' (GPs) referral behavior based on administrative panel data from 2,684,273 referrals to specialists made between 1998 and 2007. For the definition of social networks, we used information on the doctors' place and time of study and their hospital work history. We found that GPs referred more patients to specialists within their personal networks and that patients referred within a social network had fewer follow-up consultations and less inpatient days thereafter. The effects on patient outcomes (e.g. waiting periods, days in hospital) of referrals within personal networks and affinity-based networks differed. Specifically, whereas empirical evidence showed a concentration on high-quality specialists for referrals within the personal network, suggesting that referrals within personal networks overcome information asymmetry with respect to specialists' abilities, the empirical evidence for affinity-based networks was different and less clear. Same-gender networks tended to refer patients to low-quality specialists.

Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine.

There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.

Antiviral treatment of chronic hepatitis C in clinical routine.

OBJECTIVE: Pegylated interferon plus ribavirin is the standard treatment for chronic hepatitis C. Sustained virological response (SVR) rates of up to 60% are reported in randomized controlled trials, but it is unclear whether the results from such trials are reproducible in the clinical routine setting. We investigated consecutive treatment-naïve chronic hepatitis C patients at our center to examine the efficacy of treatment with pegylated interferon plus ribavirin in clinical routine. MATERIALS AND METHODS: Between 2000 and 2006 we treated a total of 219 patients with pegylated interferon alpha (2a or 2b) and ribavirin (800-1200 mg/d). Among them, 34.8% of patients infected with HCV genotypes 1/4/6 and 18.4% of those with genotypes 2/3 had advanced fibrosis or cirrhosis (F3-F4). For analysis of outcome we subdivided our series into two groups of patients: those who fulfilled standard inclusion criteria in randomized controlled trials and those who did not. RESULTS: The overall SVR rate was 44.3%. In patients with F0-F2 an SVR was achieved in 52.5%; in those with F3-F4 the SVR rate was 20.8%. In patients infected with genotypes 1/4/6 the SVR rate was 35.4% (SVR: F0-F2 47.7%; F3-F4 19.6%); in those with genotypes 2/3 the rate was 67.8%. The SVR rate in patients with unfavorable baseline factors was significantly lower (32.4% vs. 50%; P = 0.017) and they were more likely to be non-responders (30.9% vs. 13.8%). CONCLUSION: In everyday clinical practice, up to one-third of patients show unfavorable baseline factors for antiviral therapy, resulting in worse therapeutic outcome. Differences in therapeutic outcome are influenced by patient selection and by the proportion and severity of the underlying liver disease.

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection.

BACKGROUND/AIMS: Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in naïve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin. METHODS: Patients enrolled in this randomized, placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum I, 24-h HCV-RNA decline >1.4-log10; II, 0.8-1.39-log10; III, <0.8-log10; a reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (F0/1/2 vs. F3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1000-1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N = 114) or placebo (N = 95) for 48 weeks. RESULTS: Week-24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7%) or placebo (65.7%), as were sustained virological response rates at week 72 (46.5 and 51.6%, respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome. CONCLUSIONS: Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.

Warm glow, free-riding and vehicle neutrality in a health-related contingent valuation study.

Criticism of contingent valuation (CV) stresses warm glow and free-riding as possible causes for biased willingness to pay figures. We present an empirical framework to study the existence of warm glow and free-riding in hypothetical WTP answers based on a CV survey for the measurement of health-related Red Cross services. Both in conventional double-bounded and spike models we do not find indication of warm glow phenomena and free-riding behaviour. The results are very robust and insensitive to the applied payment vehicles. Theoretical objections against CV do not find sufficient empirical support.

Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease.

BACKGROUND & AIMS: A 5-fold increase of hepatic copper concentration is considered as the best available test for diagnosis of hepatic Wilson's disease (WD). However, the sensitivity and specificity of this test have never been fully investigated. METHODS: Copper content was measured by flame atomic absorption spectroscopy in 114 liver biopsies obtained at diagnosis of WD, in 219 patients with noncholestatic liver diseases (including 144 with chronic hepatitis C and 44 with nonalcoholic fatty liver disease), and in 26 without evidence of liver disease. RESULTS: Liver copper content was >250 microg/g in 95 WD patients (83.3%), between 50 and 250 microg/g in 15, and below 50 microg/g in 4. It did not correlate with age (r(2) = .003), the grade of fibrosis, or the presence of stainable copper. Liver copper content was >250 or between 50 and 250 microg/g in 3 (1.4%) and 20 (9.1%) of 219 patients with noncholestatic liver diseases, respectively. By lowering the cutoff from 250 to 75 microg/g, the sensitivity of liver copper content to diagnose WD increased from 83.3% (95% confidence interval, 75.2%-89.6%) to 96.5% (91.3%-99.1%), but the specificity decreased from 98.6% (96.0%-99.7%) to 95.4% (91.8%-97.8%). CONCLUSIONS: There is no gold standard for the diagnosis of WD. Liver copper content is a useful parameter, but a value below 250 microg/g does not exclude WD. Diagnosis requires the combination of a variety of clinical and biochemical tests.

Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents.

In patients with liver cirrhosis, implantation of a transjugular intrahepatic shunt (TIPS) leads to reduction of portal pressure, but not of mortality compared with other therapies. The high stenosis rates of conventional bare stents causes high reintervention rates and costs and may be correlated with poor survival. ePTFE-covered stentgrafts provide much improved patency rates, but their impact on survival is unclear. All suitable patients receiving either bare TIPS (419/466) or undergoing implantation of ePTFE endoprostheses (89/100) in several centers in Austria up to 2002 were included in this retrospective analysis. Both patient groups were compared regarding survival with Kaplan-Meier and Cox regression analysis. Unmatched and 1:1-matched survival analyses were performed. Patients undergoing ePTFE stentgraft implantation had significantly higher survival rates in all analyses. The 3-month, 1-year, and 2-year survival rates were 93%, 88%, and 76% for the ePTFE-group and 83%, 73%, and 62% for conventional TIPS patients, respectively. The matched survival analyses validated these findings. The model of the stent, patient age, and Child-Pugh Class (CPC) were independent predictors of survival. In conclusion, patients undergoing ePTFE-endoprosthesis implantation had higher survival rates within 2 years after TIPS-implantation. This may be the result of improved patency rates after correct placement (up to the inferior caval vein [ICV]) of the ePTFE stentgraft. These data should be validated in a prospective series.

Mutations of the HFE gene in patients with hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients with genetic hemochromatosis may be at risk for HCC, but limited information is available on the relationship of HCC and heterozygosity for the HFE gene mutations. METHODS: HFE mutations (C282Y and H63D) were assessed in 162 consecutive patients (131 men/31 women) with HCC. A total of 159 patients had cirrhosis. The most common etiologies of cirrhosis were chronic viral hepatitis (hepatitis C 39%, hepatitis B 9%) and alcoholic liver disease (36%). RESULTS: Five patients were C282Y homozygotes, four C282Y/H63D compound heterozygotes, and three H63D homozygotes. The C282Y and H63D allele frequencies in HCC were 8.3 (95% confidence limit = 5.3-11.3) and 11.1 (7.8-14.6), respectively, and not different from previously published data in healthy subjects or patients with chronic hepatitis C in Austria. Furthermore, there was no difference in the age at diagnosis in patients with or without HFE gene mutations. C282Y homozygotes had a 19-fold increased risk to develop HCC. In contrast, all other HFE allele constellations were not associated with such a risk. CONCLUSIONS: Except for C282Y homozygotes, HFE gene mutations do not increase the risk to develop HCC in patients with cirrhosis.

Impact of high-dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy.

BACKGROUND/AIMS: Initial high-dose interferon-alpha induction therapy in combination with ribavirin improves sustained response rates in treatment-naïve patients. This prospective, randomized, controlled study tested whether non-responders or relapsers to interferon monotherapy also benefit from induction therapy. METHODS: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1-1.2 g ribavirin/day throughout the whole study. RESULTS: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non-1 than in those with genotype 1. CONCLUSION: High-dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.