Rebleeding in peptic ulcer bleeding - a nationwide cohort study of 19,537 patients.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB). The associated prognosis remains rather unclear because previous studies generally also included non-ulcer lesions. OBJECTIVE: We aimed to identify predictors for rebleeding; clarify the prognostic consequence of rebleeding; and develop a score for predicting rebleeding. METHODS: Nationwide cohort study of consecutive patients presenting to hospital with PUB in Denmark from 2006-2014. Logistic regression analyses were used to identify predictors for rebleeding, evaluate the association between rebleeding and 30-day mortality, and develop a score to predict rebleeding. Patients with persistent bleeding were excluded. RESULTS: Among 19,258 patients (mean age 74 years, mean ASA-score 2.4), 10.8% rebled, and 10.2% died. Strongest predictors for rebleeding were endoscopic high-risk stigmata of bleeding (Odds Ratio (OR): 2.12 [95% Confidence Interval (CI): 1.91-2.36]), bleeding from duodenal ulcers (OR: 1.87 [95% CI: 1.69-2.08]), and presentation with hemodynamic instability (OR: 1.55 [95% CI: 1.38-1.73]). Among patients with all three factors (7.9% of total), 24% rebled, 50% with rebleeding failed endoscopic therapy, and 23% died. Rebleeding was associated with increased mortality (OR: 2.04 [95% CI: 1.78-2.32]). We were unable to develop an accurate score to predict rebleeding. CONCLUSION: Rebleeding occurs in ∼10% of patients with PUB and is overall associated with a two-fold increase in 30-day mortality. Patients with hemodynamic instability, duodenal ulcers, and high-risk endoscopic stigmata are at highest risk of rebleeding. When rebleeding occurs in such patients, consultation with surgery and/or interventional radiology should be obtained prior to repeat endoscopy.

Investigating hypozincemia and validity of plasma zinc measurements in infected patients.

Hypozincemia is a well-known phenomenon in patients with infection caused by the activation of the acute phase response (APR). Zn status is still based upon plasma Zn levels in venous blood samples. Recent trials have questioned the validity of this measurement in infected patients. The aim of this study was to assess plasma levels of Zn, albumin and Zinc-binding capacity in patients during and following infection. Furthermore, to assess if an assay for albumin-corrected Zn could potentially replace or add knowledge to existing tools for assessment of Zinc-status. A prospective clinical observational trial was conducted. Associations between P-Zn, -Albumin, -Albumin-corrected Zn and Zn binding capacity were analyzed. Analyzes were based upon two venous blood samples drawn during and following infection, respectively. Twenty-three patients admitted to a medical ward showing paraclinical signs of infection were included in the study. Significantly lower levels of Zn and albumin were found during infection compared with the levels post-infection. These findings corresponded to the changes found in Zn binding capacity. About 52% of patients were deemed Zn deficient by plasma Zn levels during infection but after applying the correction for P-Albumin, all patients were found to be within normal ranges of Zn levels. Furthermore, we found no statistically significant difference between albumin-corrected Zn during infection and P-Zn post-infection. The new assay was found to accurately estimate the 'true' Zn levels in infected patients. Based on our findings, we propose albumin-corrected P-Zn as a promising new tool, which may result in more precise diagnostics and treatment.

Albumin-corrected Zn and available free Zn-binding capacity as indicators of Zn status - potential for clinical implementation.

We have established and describe two measurement procedures to diagnose possible zinc (Zn) deficiency; albumin-corrected Zn concentration and available free Zn-binding capacity. Reference intervals for both biomarkers were established in healthy adults from the Danish population. The clinical usefulness of the measurement procedures was investigated in patients with cirrhosis and in patients given parenteral nutrition due to short bowel syndrome. The results of both methods indicate that there is a risk of overdiagnosing Zn deficiency based on low plasma Zn concentrations. Needless Zn supplementation may thus be avoided by using the albumin-corrected Zn concentration or available free Zn-binding capacity.

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients.

First-degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk-assessment and management of high-risk individuals. Using a Danish cohort of 27 FPC families, we performed whole-genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer-related genes and cancer-driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes were enriched by gene clusters encoding for extracellular matrix and associated proteins. PTV genes were over-represented by functions related to transport of small molecules, innate immune system, ion channel transport, and stimuli-sensing channels. In conclusion, FDRs of FPC patients carry rare germline variants related to cancer pathogenesis that may contribute to increased susceptibility to PDAC. The identified variants may potentially be useful for risk prediction of high-risk individuals in predisposed families.

Hypotension develops one to two hours before other symptoms in peptic ulcer rebleeding; a matched cohort study.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB) and is associated with increased mortality. Blood pressure and heart rate are two easy non-invasive measurements to evaluate the hemodynamics and therefore a standard observation during hospitalization. OBJECTIVE: We aimed to investigate the dynamics of systolic blood pressure and heart rate up to time of peptic ulcer rebleeding. DESIGN: Retrospective matched cohort study. Hemodynamics in patients with peptic ulcer rebleeding was compared to hemodynamics in a matched control group consisting of patients with PUB without rebleeding. Blood pressure and heart rate in the six hours up to diagnosis of rebleeding was compared with baseline in the case cohort as well as with the matched control group. RESULTS: Thirty-eight patients with peptic ulcer rebleeding and 66 controls were included. Mean age was 75 years, 62% were males and 30-day mortality was 23%. Baseline systolic blood pressure in cases was 114 mmHg. Compared to baseline, we found significant decrease in systolic blood pressure two hours before rebleeding (4 mmHg; p = 0.041) and one hour before rebleeding (14 mmHg; p = 0.0002). Mean systolic blood pressure 30 min before rebleeding was 89 mmHg. No significant change was found in heart rate (p = 0.99). In the control group no change was found in systolic blood pressure or heart rate. CONCLUSION: In patients with peptic ulcer rebleeding, hypotension develops 1-2 h before other symptoms of rebleeding. Thus, close monitoring of blood pressure is needed in order to ensure early identification of rebleeding in high-risk patients.

Analysis of patterns of bacteremia and 30-day mortality in patients with acute cholangitis over a 25-year period.

INTRODUCTION: Acute cholangitis (AC) is a condition of bacterial infection in the biliary tract with a high mortality rate of around 10%. Direct association between presence of bacteremia and 30-day mortality among AC patients is sparsely investigated and remains unclear. AIMS AND METHODS: Our aim was to investigate association between bacteremia and 30-day mortality among patients with AC included over a period of 25 years. All AC patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) at Odense University Hospital, between 1 January 1990 and 31 October 2015, were identified using a prospective ERCP database. Blood culture results from the patients along with antimicrobial resistance patterns were collected from a bacteremia research database. RESULTS: During the study period, 775 consecutive AC patients underwent ERCP and blood cultures were collected from 528 patients. Among these patients 48% (n = 260) had bacteremia. Overall, 30-day mortality in patients with blood cultures performed was 13% (n = 69). In patients with bacteremia, 30-day mortality was 19% (n = 49), compared to 7% (n = 20) in patients without bacteremia (p < .01). Presence of bacteremia was associated with increased 30-day mortality (OR [95% CI]: 3.43 [1.92-6.13]; p < .01) following adjustment for confounding factors. Among the species, bacteremia with Enterobacter cloacae was significantly associated with increased 30-day mortality (OR [95% CI]: 2.97 [1.16-7.62]; p = .02). CONCLUSION: Our results indicate that presence of bacteremia was associated with a nearly fourfold increase in 30-day mortality among AC patients.

How dyspepsia, gastroesophageal reflux symptoms, and overlapping symptoms affect quality of life, use of health care, and medication - a long-term population based cohort study.

BACKGROUND AND AIM: The prevalence of gastroesophageal reflux symptoms (GERS) and dyspepsia is high. Overlapping of GERS and dyspepsia has been described to affect quality of life. However, studies are few. This long-term population-based study evaluates how GERS, dyspepsia, and overlapping symptoms, affect quality of life, and the use of health care and medication. METHODS: This study presents data for the control group of the randomised population study, HEP-FYN. At baseline 10,000 individuals, aged 40-65 years, received questionnaires at baseline and after 1, 5 and 13 years. The questionnaire included questions regarding demographics, use of health care resources, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and the Short-Form 36-Item Health Survey (SF-36) to assess quality of life. RESULTS: Complete data was available for 4.403 individuals at 13-year follow-up. Of these 13.6% reported GERS only, 11.6% dyspepsia only, and 27.1% overlapping symptoms during follow-up. Individuals reporting overlapping symptoms had compared to individuals reporting GERS only or dyspepsia only more visits at general practitioner (last year:16.7% vs. 8.5% vs. 12.3%), more sick leave days (last month: 4.3% vs. 2.9% vs 0.7%), used more ulcer drugs (last month: 30.5% vs 16.4% vs 9.4%). In addition, individuals with overlapping symptoms reported a lower quality of life in all eight dimensions of SF-36 compared to individuals with GERS alone or dyspepsia alone. CONCLUSIONS: Overlapping symptoms was associated with lower quality of life scores and substantial use of health-care resources. Having solely GERS affected quality of life and health care use least.

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.

Unchanged mortality in patients with acute cholangitis despite an increase in malignant etiologies - a 25-year epidemiological study.

Background and aims: Acute cholangitis (AC) is a rare but serious condition, with an incidence of 7.0 per 10,000 people and mortality rates up to 10%. The aim of this study was to describe changes in obstruction etiology, comorbidities, clinical factors, and mortality among AC patients during a 25-year period. Methods: Using a database of 11,563 consecutive ERCP-procedures performed from 1990-2015 at Odense University Hospital, we identified all AC cases during that period. Clinical and epidemiological data were collected from the database and the Danish Patient Registry. Association with 30-day mortality was investigated using multiple logistic regression analysis with adjustment for confounding factors. Results: In total, 775 consecutive and individual cases of AC were included. Among cases, 42% (n = 326) were of malignant etiology, with an increasing incidence over time (regression coefficient [95% CI]: 0.03 [0.01-0.04] per year; p = .01). Mean Charlson Comorbidity Index was 1.4, with an increase over time (regression coefficient [95% CI]: 0.04 [0.03-0.05] per year; p < .01). Malignant obstruction etiology was associated with 30-day mortality (OR [95% CI]: 1.11 [1.04-1.18]; p < .01). Overall 30-day mortality was 12% (n = 91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time (OR [95% CI]: 1 [1-1.00]; p = .91 per year). Conclusion: Significant increases in the incidence of malignant obstruction etiology and severity of comorbidities among AC patients were observed during the study period. Despite those findings, 30-day mortality remained unchanged, potentially reflecting a general improvement in the management of AC.

Association between early ERCP and mortality in patients with acute cholangitis.

BACKGROUND AND AIMS: Acute cholangitis (AC) is associated with high mortality of up to 10%. The association between timing of ERCP and mortality in patients with AC remains unclear. The aim of this study was to investigate whether early ERCP within 24 hours was associated with improved survival. METHODS: All patients who underwent ERCP at Odense University Hospital, Denmark, between March 2009 and September 2016 were identified using a prospective ERCP database. Clinical data were collected from medical records. Patients fulfilling the Tokyo Guidelines 2013 criteria and for whom a detailed review of medical records revealed evidence of AC were included. We investigated the association between ERCP within 24 hours and 30-day mortality using logistic regression analysis with adjustment for confounding factors. RESULTS: A total of 4066 consecutive patients underwent ERCP during the study period, and 166 patients fulfilled the inclusion criteria. Forty-eight patients (29%) underwent ERCP within 24 hours from the time of hospitalization, and 118 patients (71%) underwent later ERCP. Patients undergoing ERCP within 24 hours were younger (medians: 65 vs 73 years; P = .01) and had a higher heart rate (medians: 95 vs 90 beats/minute; P = .02). Overall 30-day mortality was 16% (n = 27). Mortality was 8% (n = 4) among patients undergoing early ERCP and 19% (n = 23) among patients undergoing later ERCP (P = .10). After adjustment for confounding factors, performance of ERCP within 24 hours was associated with lower 30-day mortality (odds ratio, 0.23; 95% confidence interval, 0.05-0.95; P = .04). CONCLUSION: Our results indicate that early ERCP within 24 hours is associated with lower 30-day mortality in patients with AC.

Arterial lactate does not predict outcome better than existing risk scores in upper gastrointestinal bleeding.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a frequent medical emergency and several scoring systems are developed to help risk-stratify patients. We aimed to investigate if elevated arterial lactate (AL) was associated with 30-day mortality, need for hospital-based intervention, or rebleeding. Furthermore, we compared the performance of AL with existing scoring systems and examined if incorporation of AL could improve their predictive ability. MATERIALS AND METHODS: Retrospective cohort study of 331 consecutive patients admitted with UGIB during a one-year period. Multivariate analyses were performed to evaluate the association between AL and outcomes. Receiver operating characteristic curves were used to compare AL with existing scoring systems and to test if incorporation of AL could significantly increase their performance. RESULTS: AL was significantly associated with mortality (p = .001), need for hospital-based intervention (p = .005), and rebleeding (p = .031). In predicting mortality and rebleeding, AL performed equally to existing scoring systems, however, inferior to all, in predicting need for intervention. Two of the scoring systems were marginally improved in predicting mortality if AL was included. CONCLUSIONS: AL is associated with adverse outcomes in patients with UGIB, but has only similar or inferior ability to predict relevant clinical outcomes compared to existing scoring systems. Although AL could enhance performance of two scorings systems in predicting mortality, it does not have an apparent clinical significance. Thus, our data does not support routine measurement of AL in patients with UGIB.

Effects of Community Screening for Helicobacter pylori: 13-Year Follow-Up Evaluation of a Randomized Controlled Trial.

BACKGROUND & AIMS: Helicobacter pylori eradication improves the prognosis of peptic ulcer disease (PUD), dyspepsia, and possibly gastric cancer. H pylori screening tests are accurate and eradication therapy is effective. H pylori population screening seems attractive. The aim of this study was to evaluate the long-term effect of H pylori population screening and eradication on dyspepsia prevalence and the incidence of PUD, and as secondary outcomes to assess the effect on health care consumption and quality of life. METHODS: At baseline in 1998 to 1999, 20,011 individuals aged 40 to 65 years were randomized to H pylori screening and eradication or a control group with no screening. Both groups received a questionnaire on dyspepsia and quality of life. Register data were obtained for all randomized individuals. RESULTS: The baseline questionnaire response rate was 63%. Of the 5749 individuals screened, 1007 (17.5%) were H pylori positive. Complete symptom data were obtained for 8658 (69%) individuals after 13 years. Dyspepsia prevalence decreased in both groups during the follow-up period, but multivariate analysis showed no effect of H pylori screening and eradication (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04); compared with usual care. Intention-to-treat and per-protocol analyses of register data provided similar results. H pylori screening neither reduced PUD incidence significantly (adjusted odds ratio, 0.88; 95% confidence interval, 0.70-1.11) nor did it have a beneficial effect on health care consumption. H pylori screening had no long-term effect on quality of life. CONCLUSIONS: This randomized clinical trial with 13 years of follow-up evaluation, designed to provide evidence on the effect of H pylori population screening, showed no significant long-term effect when compared with usual care in this low-prevalence area. ClinicalTrials.gov identifier: NCT02001727.

Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study.

BACKGROUND AND AIMS: The optimal timing of endoscopy in patients with peptic ulcer bleeding (PUB) remains unclear. The aim of this study was to examine the association between timing of endoscopy and mortality in PUB. METHODS: In a nationwide cohort study based on a database of consecutive patients admitted to the hospital with PUB in Denmark, patients were stratified according to the presence of hemodynamic instability at presentation and American Society of Anesthesiologists (ASA) score. Using descriptive statistics and logistic regression analyses, we identified optimal time frames for endoscopy and analyzed the association between timing of endoscopy and in-hospital mortality after adjusting for confounding factors. RESULTS: In total, 12,601 patients were included. We did not find any universal association between timing of endoscopy and mortality in hemodynamically stable patients with an ASA score of 1 to 2. In hemodynamically stable patients with an ASA score of 3 to 5, endoscopy 12 to 36 hours after admission to the hospital was associated with lower in-hospital mortality (OR, .48; 95% CI, .34-.67) compared with endoscopy outside this time frame. In patients with hemodynamic instability, endoscopy 6 to 24 hours after admission to the hospital was associated with lower in-hospital mortality (OR, .73; 95% CI, .54-.98) compared with endoscopy outside this time frame. CONCLUSIONS: Timing of endoscopy is associated with mortality in patients with PUB and an ASA score of 3 to 5 or hemodynamic instability. Our findings suggest that in these patients, a period of time to optimize resuscitation and manage comorbidities before endoscopy may improve outcome.

Internal dysregulation of the renin system in patients with stable liver cirrhosis.

Sodium retention in cirrhosis is associated with changes in the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and the glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute reactions of RAAS and SNS to volume expansion are qualitatively intact, but occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and renal responses to central blood volume changes were studied in cirrhotic patients and healthy controls. In patients, baseline plasma renin concentration (PRC) was elevated 5-fold compared to controls (p < .001); it increased during standing (+144%, p < .001) and remained elevated during subsequent sitting (+118%, p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated significantly (14 ± 2 vs. 9 ± 2 pg/mL) in contrast to plasma aldosterone (pAldo, +160%, p < .001). During orthostatic RAAS activation, the rise in pAngII per unit increase in PRC was 0.04 pg AngII/mIU and 0.48 pg AngII/mIU in patients and controls, respectively (p < .001); similarly, the change in pAldo per unit change in pANGII was 3.6 in patients and 14.5 pg/pg in controls (p < .001). Plasma noradrenaline was elevated in the patients, but the dynamic changes were virtually identical to those of controls. During standing, abrupt decreases in renal blood flow (-63%, p < .001) and GFR (-42% p < .04) occurred only in patients. In conclusion, in stable cirrhosis, static and dynamic dysregulation exists within the RAAS; in the supine position pAngII levels are inappropriately low, and the AngII-mediated regulation of aldosterone secretion is severely impeded. In cirrhotic patients, profound reductions in renal blood flow and GFR occur during standing.

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.

Performance of new thresholds of the Glasgow Blatchford score in managing patients with upper gastrointestinal bleeding.

BACKGROUND & AIMS: Upper gastrointestinal hemorrhage (UGIH) is a common cause of hospital admission. The Glasgow Blatchford score (GBS) is an accurate determinant of patients' risk for hospital-based intervention or death. Patients with a GBS of 0 are at low risk for poor outcome and could be managed as outpatients. Some investigators therefore have proposed extending the definition of low-risk patients by using a higher GBS cut-off value, possibly with an age adjustment. We compared 3 thresholds of the GBS and 2 age-adjusted modifications to identify the optimal cut-off value or modification. METHODS: We performed an observational study of 2305 consecutive patients presenting with UGIH at 4 centers (Scotland, England, Denmark, and New Zealand). The performance of each threshold and modification was evaluated based on sensitivity and specificity analyses, the proportion of low-risk patients identified, and outcomes of patients classified as low risk. RESULTS: There were differences in age (P = .0001), need for intervention (P < .0001), mortality (P < .015), and GBS (P = .0001) among sites. All systems identified low-risk patients with high levels of sensitivity (>97%). The GBS at cut-off values of ≤1 and ≤2, and both modifications, identified low-risk patients with higher levels of specificity (40%-49%) than the GBS with a cut-off value of 0 (22% specificity; P < .001). The GBS at a cut-off value of ≤2 had the highest specificity, but 3% of patients classified as low-risk patients had adverse outcomes. All GBS cut-off values, and score modifications, had low levels of specificity when tested in New Zealand (2.5%-11%). CONCLUSIONS: A GBS cut-off value of ≤1 and both GBS modifications identify almost twice as many low-risk patients with UGIH as a GBS at a cut-off value of 0. Implementing a protocol for outpatient management, based on one of these scores, could reduce hospital admissions by 15% to 20%.

The excess long-term mortality in peptic ulcer bleeding is explained by nonspecific comorbidity.

OBJECTIVE: Previous studies have concluded that peptic ulcer bleeding (PUB) is associated with increased long-term mortality. The underlying mechanism of this excess mortality is poorly understood. The aim of the present study was to examine if PUB patients have an increased long-term mortality compared to a matched control group when adjusting for comorbidity and socioeconomic status. Additionally, we identified predictive factors for mortality and examined causes of death. MATERIAL AND METHODS: We performed an observational study, comparing consecutive patients admitted with PUB with a matched control cohort from the source population. Predictors of mortality were identified using proportional hazards models. Causes of death were retrieved from death certificates. Long-term mortality was analyzed with adjustment for Charlson comorbidity index (CCI) and average income in residence municipality using proportional hazards models. RESULTS: We included 455 PUB cases and 2224 control subjects. Median follow up was 9.7 years, and median survival for the PUB and control cohorts was 7 and 12 years, respectively (p < 0.001). PUB patients had a higher level of comorbidity (mean CCI: 0.92 vs. 0.49; p < 0.0001). After adjustments, PUB patients had an excess mortality lasting at least 10 years after presentation. Age, comorbidity, male sex, anemia, and smoking were predictors for long-term mortality. The distribution of causes of death was similar in the two cohorts. CONCLUSION: PUB patients have an increased long-term mortality that is explained by nonspecific comorbidity.

Transcatheter arterial embolization is the first-line therapy of choice in peptic ulcer bleeding not responding to endoscopic therapy.

OBJECTIVE: In 5-10% of patients with peptic ulcer bleeding (PUB) it is impossible to achieve endoscopic hemostasis because of severe bleeding. These patients have traditionally been treated surgically. Transcatheter arterial embolization (TAE) may, however, be associated with a better outcome because of the less-invasive nature of the procedure. The aim of the present study was to identify the treatment of choice in endoscopy-refractory PUB. MATERIALS AND METHODS: A retrospective study. Consecutive patients treated with surgery or TAE for endoscopy-refractory PUB during a period of 16 years at a university hospital were included. Primary hemostasis, rebleeding rate, mortality, and complications were assessed. Mortality was compared between groups after adjustment for age, comorbidity, and anemia using logistic regression analyses. Comorbidity was quantified using the Charlson comorbidity index (CCI). RESULTS: One hundred and eighteen patients were included. Patients treated with TAE had a higher CCI (mean: 2.33 vs 1.42; p = .003), and more severe anemia (mean: 6.8 vs 7.9 g/dl; p = .007) compared with patients treated with surgery. Surgery was associated with a higher rate of primary hemostasis (100% vs 91%; p = .007), lower rate of rebleeding (15% vs 40%; p = .004) but also higher rate of complications (60% vs 38%; p = .02) than TAE. Surgery was associated with an increased mortality (Odds ratio: 3.05; p = .033) when adjusting for confounding factors and excluding patients (n = 3) who were not candidates for both interventions. CONCLUSIONS: We propose use of TAE as first-line therapy in these patients as it may be associated with lower mortality and lower rate of complications compared with surgery.

Supplementary arteriel embolization an option in high-risk ulcer bleeding--a randomized study.

OBJECTIVE: One of the major challenges in peptic ulcer bleeding (PUB) is rebleeding which is associated with up to a fivefold increase in mortality. We examined if supplementary transcatheter arterial embolization (STAE) performed after achieved endoscopic hemostasis improves outcome in patients with high-risk ulcers. MATERIAL AND METHODS: The study was designed as a non-blinded, parallel group, randomized-controlled trial and performed in a university hospital setting. Patients admitted with PUB from Forrest Ia - IIb ulcers controlled by endoscopic therapy were randomized (1:1 ratio) to STAE of the bleeding artery within 24 h or continued standard treatment. Randomization was stratified according to stigmata of hemorrhage. Patients were followed for 30 days. Primary outcome was a composite endpoint where patients were classified into five groups based on transfusion requirement, development of rebleeding, need of hemostatic intervention and mortality. Secondary outcomes were rebleeding, number of blood transfusions received, duration of admission and mortality. RESULTS: Totally 105 patients were included. Of the 49 patients allocated to STAE 31 underwent successful STAE. There was no difference in composite endpoint. Two versus eight patients re-bled in the STAE and control group, respectively (Intention-to-treat analysis; p = .10). After adjustment for possible imbalances a strong trend was noted between STAE and rate of rebleeding (p = .079). CONCLUSIONS: STAE is potentially useful for preventing rebleeding in high-risk PUB. STAE can safely be performed in selected cases with high risk of rebleeding. Further studies are needed in order to confirm these findings; ClincialTrials.gov number, NCT01125852.

A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome.

BACKGROUND & AIMS: Guidelines recommend a positive strategy based on symptom criteria to diagnose patients with irritable bowel syndrome (IBS). We conducted a randomized noninferiority trial to determine whether a positive diagnostic strategy is noninferior to a strategy of exclusion, with regard to patients' health-related quality of life (HRQOL). METHODS: We studied 302 patients (18-50 years old) from primary care who were suspected of having IBS and referred by general practitioners. Patients who fulfilled the Rome III criteria for IBS with no alarm signals were randomly assigned to groups assessed by a strategy of exclusion (analyses of blood, stool samples for intestinal parasites, and sigmoidoscopies with biopsies) or a positive strategy (analyses of blood cell count and C-reactive protein). Patients were followed for 1 year. The primary end point was difference in change of HRQOL from baseline to 1 year between groups (on the basis of the Short Form 36 health survey, physical component summary, and noninferiority margin of 3 points). Secondary outcomes were change in gastrointestinal symptoms, satisfaction with management, and use of resources. Findings of diagnostic misclassification were registered. RESULTS: A positive strategy was noninferior to a strategy of exclusion (difference, 0.64; 95% confidence interval, -2.74 to 1.45). The positive diagnostic strategy had lower direct costs. Each approach had similar effects on symptoms, satisfaction, and subsequent use of health resources. No cases of inflammatory bowel disease, colorectal cancer, or celiac disease were found. CONCLUSIONS: In diagnosing IBS in primary care, use of a positive diagnostic strategy is noninferior to using a strategy of exclusion with regard to the patients' HRQOL. Our findings support the current guideline recommendations.