Cohort profile and heritability assessment of familial pancreatic cancer: a nation-wide study.

BACKGROUND: Familial Pancreatic Cancer (FPC) is responsible for up to 10% of all cases of pancreatic ductal adenocarcinoma (PDAC). Individuals predisposed for FPC have an estimated lifetime risk of 16-39% of developing PDAC. While heritability of PDAC has been estimated to be 36% in a Nordic twin study, no heritability estimate specific on FPC has been reported. METHODS: A national cohort of Danish families with predisposition for FPC is currently included in a screening program for PDAC at Odense University Hospital. Family members included in the screening program were interviewed for pedigree data including: cases of PDAC among first-degree relatives (FDRs) and number of affected/unaffected siblings. Heritability for FPC in the predisposed families was assessed by doubling the estimated intra-class correlation coefficient (ICC) from a random intercept logistic model fitted to data on FDRs. RESULTS: Among families with predisposition for FPC, 83 cases of PDAC were identified. The median age at diagnosis of PDAC was 66 years, and median time from diagnosis to death was 7.6 months. A total of 359 individuals were found as unaffected FDRs of the 83 PDAC cases. The retrieved FDRs included a total of 247 individuals in sibship and 317 individuals in parent-offspring relatedness. We estimated an ICC of 0.25, corresponding to a narrow sense additive heritability estimate of 0.51 in the FPC family cohort. CONCLUSION: We have established a nation-wide cohort of FPC families to facilitate clinical and genetic studies on FPC. The estimated heritability of 51% prominently underlines a strong genetic background of FPC.

The cost effectiveness of Helicobacter pylori population screening-economic evaluation alongside a randomised controlled trial with 13-year follow-up.

BACKGROUND: Helicobacter pylori eradication improves dyspeptic symptoms in 8%-10%, prevents peptic ulcer and may reduce the risk of gastric cancer. Availability of a high quality diagnostic test and an effective treatment makes population screening and eradication of Helicobacter pylori an attractive option. AIM: To evaluate the cost effectiveness of Helicobacter pylori population screening and eradication. METHODS: Cost effectiveness analysis and cost utility analysis alongside randomised controlled trial with 13 years follow-up. The evaluation has a societal perspective. A random general population sample of 20 011 individuals aged 40-65 were randomised and invited in 1998-1999; 12 530 were enrolled and, of these, 8658 have been successfully followed up at 1, 5, and 13 years after intervention. Questionnaires included the quality of life instrument SF-36. From SF-36 responses an SF-6D score was derived and used for calculation of quality-adjusted life years. Register data on costs, use of health care resources and medication were obtained for all randomised individuals. The intervention was an invitation to Helicobacter pylori screening by in-office blood test; positive tests were validated by 13 C-urea breath test. Those who tested positive were offered eradication therapy. Main outcome measures were Incremental cost per quality-adjusted life year and life-years gained. RESULTS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost per screened person was higher than not screening (mean difference 11 269 DKK [95% CI: 3175-19 362]). The probability of being cost-effective was 80% at a threshold of 400 000 DKK (approximately 53,800 Euros) of willingness-to-pay per life-year gained. CONCLUSIONS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost of screening was higher than not screening.

Is screening for pancreatic cancer in high-risk groups cost-effective? - Experience from a Danish national screening program.

OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems to improve with early detection. A hereditary component has been identified in 1-10% of the PC cases. To comply with this, screening for PC in high-risk groups with a genetic disposition for PC has been recommended in research settings. DESIGN: Between January 2006 and February 2014 31 patients with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no-screening was assessed by the incremental cost-utility ratio (ICER). RESULTS: By screening the FPC group we identified 2 patients with PDAC who were treated by total pancreatectomy. One patient is still alive, while the other died after 7 months due to cardiac surgery complications. Stratified analysis of patients with HP and FPC provided ICERs of 47,156 US$ vs. 35,493 US$ per life-year and 58,647 US$ vs. 47,867 US$ per QALY. Including only PDAC related death changed the ICER to 31,722 US$ per life-year and 42,128 US$ per QALY. The ICER for patients with FPC was estimated at 28,834 US$ per life-year and 38,785 US$ per QALY. CONCLUSIONS: With a threshold value of 50,000 US$ per QALY this screening program appears to constitute a cost-effective intervention although screening of HP patients appears to be less cost-effective than FPC patients.

The Glasgow Blatchford score is the most accurate assessment of patients with upper gastrointestinal hemorrhage.

BACKGROUND & AIMS: Risk scoring systems are used increasingly to assess patients with upper gastrointestinal hemorrhage (UGIH). There have been comparative studies to identify the best system, but most have been retrospective and included small sample sizes, few patients with severe bleeding and with low mortality. We aimed to identify the optimal scoring system. METHODS: We performed a prospective study to compare the accuracy of the Glasgow Blatchford score (GBS), an age-extended GBS (EGBS), the Rockall score, the Baylor bleeding score, and the Cedars-Sinai Medical Center predictive index in predicting patients' (1) need for hospital-based intervention or 30-day mortality, (2) suitability for early discharge, (3) likelihood of rebleeding, and (4) mortality. We analyzed the area under receiver operating characteristic (AUROC) curve, sensitivity, specificity, and positive and negative predictive values for each system. The study included 831 consecutive patients admitted with UGIH during a 2-year period. RESULTS: The GBS and EGBS better predicted patients' need for hospital-based intervention or 30-day mortality than the other systems (AUROC, 0.93; P < .001) and were also better in identifying low-risk patients (sensitivity values, 0.27-0.38; specificity values, 0.099-1). The EGBS identified a significantly higher proportion of low-risk patients than the GBS (P = .006). None of the systems accurately predicted which patients would have rebleeding or patients' 30-day mortality, on the basis of low AUROC and specificity values. CONCLUSIONS: The GBS accurately identifies patients with UGIH most likely to need hospital-based intervention and also those best suited for outpatient care. The EGBS seems promising but must be validated externally. No scoring system seems to accurately predict patients' 30-day mortality or rebleeding. ClinicalTrials.gov number, NCT01589250.

Effect of a community screening for Helicobacter pylori: a 5-Yr follow-up study.

BACKGROUND: Helicobacter pylori (H. pylori) screening and eradication may reduce the incidence of gastric cancer, AND AIMS: peptic ulcer, and ulcer complications, and it may reduce symptoms in a small proportion of individuals with functional dyspepsia. This study aimed to assess the effect of community H. pylori screening and treatment on the prevalence of dyspepsia, and as secondary outcomes, the effect on dyspepsia-related health-care consumption and quality of life over 5 yr. METHODS: In 1998-1999, individuals aged 40-65 yr were randomized to H. pylori screening and treatment or to the control group. Five years later, the participants were sent a questionnaire to assess the prevalence of dyspepsia and quality of life. In addition, we obtained information from registers on the use of endoscopies and prescription medication. An economic evaluation was done alongside the randomized trial. RESULTS: Of 12,530 participants attending the study at baseline, 11,065 (88%) were traced and contacted at the 5-yr follow-up. The response rate was 94%. At baseline, 17.5% in the screened group were H. pylori-positive. The absolute reduction in dyspepsia during the first year was 4% in the screened group, whereas no change was observed in the unscreened group; this rate remained constant during the next 4 yr. Quality of life did not change. A small effect was found for dyspepsia-related consultations and sick leave days, but not on the prescription rate of ulcer drugs. A 33% lower ulcer incidence (107 ulcers vs 148 ulcers) was seen in the screened group compared to the unscreened group. CONCLUSION: A population H. pylori screening and treatment program in an H. pylori low-prevalence area had only a modest, but insignificant, effect on the rate of dyspepsia, and a modest, significant effect on the consultation rate and sick leave days for dyspepsia, but resulted in a decreased ulcer incidence. The intervention resulted in an increased cost due to H. pylori screening and treatment.

Economic evaluation of empirical antisecretory therapy versus Helicobacter pylori test for management of dyspepsia: a randomized trial in primary care.

OBJECTIVES: An economic evaluation was performed of empirical antisecretory therapy versus test for Helicobacter pylori in the management of dyspepsia patients presenting in primary care. METHODS: A randomized trial in 106 general practices in the County of Funen, Denmark, was designed to include prospective collection of clinical outcome measures and resource utilization data. Dyspepsia patients (n = 722) presenting in general practice with more than 2 weeks of epigastric pain or discomfort were managed according to one of three initial management strategies: (i) empirical antisecretory therapy, (ii) testing for Helicobacter pylori, or (iii) empirical antisecretory therapy, followed by Helicobacter pylori testing if symptoms improved. Cost-effectiveness and incremental cost-effectiveness ratios of the strategies were determined. RESULTS: The mean proportion of days without dyspeptic symptoms during the 1-year follow-up was 0.59 in the group treated with empirical antisecretory therapy, 0.57 in the H. pylori test-and-eradicate group, and 0.53 in the combination group. After 1 year, 23 percent, 26 percent, and 22 percent, respectively, were symptom-free. Applying the proportion of days without dyspeptic symptoms, the cost-effectiveness for empirical treatment, H. pylori test and the combination were 12,131 Danish kroner (DKK), 9,576 DKK, and 7,301 DKK, respectively. The incremental cost-effectiveness going from the combination strategy to empirical antisecretory treatment or H. pylori test alone was 54,783 DKK and 39,700 DKK per additional proportion of days without dyspeptic symptoms. CONCLUSIONS: Empirical antisecretory therapy confers a small insignificant benefit but costs more than strategies based on test for H. pylori and is probably not a cost-effective strategy for the management of dyspepsia in primary care.