A novel method for the translation and cross-cultural adaptation of health-related quality of life patient-reported outcome measurements.

BACKGROUND: This paper presents a novel methodology for translation and cross-cultural adaptation of health-related quality-of-life patient-reported outcome measures, incorporating the Delphi method. Specifically, we describe the process of translating the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 from English to Norwegian using this method. METHODS: The multistep translation method combined the European Organization for Research and Treatment of Cancer Quality of Life guidelines, an Expert Panel review, and the Delphi method. It comprised two independent forward- and back-translations. While the bilingual pelvic floor Expert Panel ensured rigorous cross-checking and effective cross-cultural adaptation, the addition of the Delphi method (comprising the attributes of anonymity, controlled feedback, and statistical group response) further established consensus on translated items. OUTCOMES: The application of the Delphi method in the Expert Panel phase proved adequate in producing comprehensible intermediate Norwegian versions ready for pilot testing. The Expert Panel reviewed the comments made by patients completing the instruments and offered advice to allow final translated versions to be produced and tested for measurement properties. This iterative approach, internal logic, and anonymity between rounds improved the evaluations that the panel members provided, which in turn enhanced the final translated Patient Reported Outcome Measures (PROMs). CONCLUSIONS: To our knowledge, this work represents the first demonstration of the application of an Expert Panel review incorporating a Delphi method to assess health-related quality-of-life instruments. The controlled feedback approach, iterative nature, internal logic, and anonymity of the Delphi consensus method appeared to ensure a good cross-cultural adaptation of these PROMs.

Serological antibodies and surgery in a population-based inception cohort of Crohn's disease patients - the IBSEN study.

Introduction: Serological antibodies have been associated with complicated disease course in Crohn's disease (CD), including the need for surgery.Aim: The aim of this study was to investigate if a panel of relevant antibodies could predict surgery in a prospective population-based cohort of patients with CD.Methods: The population-based IBSEN cohort has been followed prospectively for 20 years. At the 10- and 20-year follow-up, the following panel of serological antibodies was analysed: pANCA, ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1. At the 20-year follow-up or until lost to follow-up, all CD-related surgeries were registered.Results: Serum was available from 159 patients at 10-year follow-up and 135 patients at 20-year follow-up. In 113 patients, serum was available at both time points. No significant change of antibody status (positive vs. negative) was found from 10-year to 20-year follow-up. Negative pANCA, positive ASCA IgA and positive ASCA IgG at 10-year follow-up were all individually associated with increased risk for CD-related surgery. There was no association between anti-OmpC, anti-I2 or anti-CBir1 and CD-related surgery. In a multiple regression model including disease location and behaviour, only stricturing or penetrating disease behaviour and negative pANCA remained significantly associated with higher odds for surgery.Conclusion: Positive ASCA IgA and IgG, and negative pANCA were associated with higher odds for CD-related surgery in univariate analysis. Since disease phenotype changes during the disease course, while serological antibodies are stable, our results support the use of pANCA, ASCA IgA and ASCA IgG as prognostic markers in CD.

Clinical relevance of pancreatobiliary and intestinal subtypes of ampullary and duodenal adenocarcinoma: Pattern of recurrence, chemotherapy, and survival after pancreatoduodenectomy.

BACKGROUND: The clinical relevance of the classification of ampullary adenocarcinoma (AC) into pancreatobiliary (PB) or intestinal (Int) subtypes has not been resolved. METHODS: Clinicopathological factors, survival, and localization and treatment of recurrence were investigated for patients with AC and duodenal adenocarcinoma (DC) treated by pancreatoduodenectomy from 2000 to 2015. RESULTS: A total of 109 AC (45 PB, 64 Int) and 71 DC (all Int) were identified. Median overall survival (OS) for ACPB vs DC vs ACInt was 43.6 vs 51 vs 75 months, respectively. ACPB had significantly shorter OS than ACInt (p = 0.036). However, for AC stage (HR = 2.39; 95 %CI 1.23-4.64, p = 0.010) was the only factor associated with mortality risk in multivariate analysis. Localization of recurrence (n = 88) was predominantly distant (ACPB 81.5%; ACInt 92%; DC 91.7%, p = 0.371). Post-recurrence survival (PRS) for ACPB, ACInt and DC did not differ (6.9 vs 9.2 vs 7.5 months, p = 0.755). Best supportive care or palliative chemotherapy were offered for recurrent disease to 44.5%/48.1% for ACPB, 40%/56% for ACInt, and 41.7%/52.8% for DC (p = 0.947). The choice of chemotherapy regimen varied considerably. Five patients underwent surgical resection or ablation with curative intent. All deaths among ACPB were caused by recurrent disease, whereas 29.4% of ACInt and 23.1% of DC deaths was non-cancer related or caused by other specific cancer. CONCLUSION: ACPB, ACInt and DC have similar recurrence patterns and PRS. The difference in survival between ACPB and ACInt was not statistically significant when stratified by stage. The optimal chemotherapy in patients with recurrent AC remains undefined.

Real world data on effectiveness, safety and therapeutic drug monitoring of vedolizumab in patients with inflammatory bowel disease. A single center cohort.

BACKGROUND AND AIMS: The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness. METHODS: This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy. RESULTS: In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients. CONCLUSION: Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.

Peripheral arthritis in patients with long-term inflammatory bowel disease. Results from 20 years of follow-up in the IBSEN study.

OBJECTIVES: Peripheral arthritis and related musculoskeletal manifestations, often classified as peripheral spondyloarthritis, are frequently seen in patients with inflammatory bowel disease (IBD). Few long-term studies have reported on the prevalence of these conditions. The aim of this study was to determine the prevalence of IBD-related peripheral arthritis and peripheral spondyloarthritis in IBD patients during 20 years of disease course, and to assess whether these conditions were associated with the intestinal IBD severity and activity. MATERIALS AND METHODS: In an inception cohort (the IBSEN study), IBD patients were followed prospectively for 20 years. At the 5 year follow-up the patients underwent a rheumatological examination and at the 20 year follow-up they completed a questionnaire with identical questions. When peripheral arthritis was characteristic and not explained by other specific diagnoses, it was defined as IBD-related peripheral arthritis. The Assessment of Spondyloarthritis International Society criteria were used to define peripheral spondyloarthritis, including patients with peripheral arthritis, enthesitis and/or dactylitis. RESULTS: After 20 years of follow-up, 441 patients were included (296 ulcerative colitis and 145 Crohn's disease). The prevalence of IBD-related peripheral arthritis was 17.2% and peripheral spondyloarthritis 27.9% during the disease course. IBD severity and activity were not different between those with a history of IBD-related peripheral arthritis or peripheral spondyloarthritis and those without. A higher proportion of women had IBD-related peripheral arthritis and peripheral spondyloarthritis. CONCLUSION: During 20 years of disease course, more than every sixth patient had suffered from IBD-related peripheral arthritis and every fourth from peripheral spondyloarthritis.

Switching from originator to biosimilar infliximab - real world data of a prospective 18 months follow-up of a single-centre IBD population.

BACKGROUND AND AIMS: Long-term data regarding switching from originator infliximab to biosimilar CT-P13 are sparse. Concerns about increased immunogenicity after switching have been raised. We aimed to study the effectiveness, safety and immunogenicity after switching from originator infliximab to CT-P13 in a real-world IBD population with 18 months prospective follow-up. METHODS: All adult IBD patients treated with originator infliximab at the Department of Gastroenterology, Oslo University Hospital, were switched to CT-P13 and followed prospectively for 18 months. The primary endpoints were (i) the proportion of patients remaining on CT-P13 18 months after switching and (ii) immunogenicity during 18 months after switching. The secondary endpoints included (i) adverse events, (ii) changes in disease activity, C-reactive protein, anaemia, faecal calprotectin, infliximab dose and interval and p-infliximab. RESULTS: In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. Altogether, 130 (91%) remained on CT-P13 throughout 18 months. Two patients developed ADAs at moderate level and discontinued CT-P13. Another 10 patients discontinued CT-P13 (two due to loss of response without ADAs, four due to adverse events, and four in remission and a personal wish to stop). There was no overall change in disease activity scores or in the other studied variables except for p-infliximab, which increased significantly. CONCLUSIONS: The present study provides valuable evidence for the safety and effectiveness of switching from originator to biosimilar infliximab over a prolonged period of 18 months and demonstrates that switching was well tolerated and did not affect the long term clinical outcome.

Clinical Outcome of Patients With High-Risk Endometrial Carcinoma After Treatment With Chemotherapy Only.

OBJECTIVES: Adjuvant treatment of high-risk endometrial cancer (EC) is still controversial. Several studies have tried to clarify the best treatment strategy, and guidelines have been made, but no study to date has shown a survival benefit for radiation over chemotherapy. We aimed to evaluate the outcome of high-risk EC patients treated with adjuvant chemotherapy only in a population where the routine administration of adjuvant radiotherapy was omitted. METHODS: This is a retrospective study including 230 EC patients with International Federation of Gynecology and Obstetrics stage I type II, stage Ib type I/G3, stage II, and IIIc treated at Oslo University Hospital between 2005 and 2012. Standard treatment was hysterectomy, bilateral salpingo-oophorectomy and at least pelvic lymphadenectomy followed by adjuvant chemotherapy. RESULTS: Of the 230 high-risk patients, standard treatment was given to 146 patients (63.5%): 60 patients in stage I, 10 patients in stage II, and 76 patients in stage IIIc. Only 10% of patients with stage I disease relapsed, with 3.3% locoregional relapses and 6.7% distant relapses. Recurrence rate in stage IIIc was 39.5%, with 7.9% isolated vaginal and 31.6% distant relapses. The 3-year disease-free survival was 92% for stage I, 80% for stage II, and 60% for stage IIIc disease. In the total population, 55 patients had International Federation of Gynecology and Obstetrics stage Ia, 43 Ib, 42 stage II, and 90 stage IIIc disease. Recurrence rate in the total population was 29.6%, with 9.6% isolated vaginal recurrences, 1.7% recurrences located in the pelvis, and 18.3% distant recurrences. CONCLUSIONS: Patients with high-risk EC have acceptable vaginal/pelvic control rates after adjuvant chemotherapy. However, prognosis remains poor for patients with stage IIIc disease, also after chemotherapy.

Symptom Experience and Self-rated Physical Functioning in Patients With Ovarian Cancer Receiving Chemotherapy: A Longitudinal Study.

OBJECTIVES: In this longitudinal study, we investigated occurrence of multiple symptoms during chemotherapy in patients with ovarian cancer. We also evaluated whether self-rated physical functioning, selected demographic, and clinical variables were associated with symptom burden over time. METHODS AND MATERIALS: In total, 82 patients provided longitudinal data (4 time points) by completing questionnaires including the Memorial Symptom Assessment Scale, the Karnofsky Performance Status Scale, and the Self-Administered Comorbidity Questionnaire. Demographic and clinical data were collected from medical records. Karnofsky Performance Status Scale score of less than 80 was defined as low and Karnofsky Performance Status Scale score 80 or higher as high physical functioning. Possible associations between the most frequent symptoms and selected variables were modeled using binary logistic regression for repeated measures. RESULTS: Palliative treatment was the main reason for treatment for 85% of the patients. Sixty percent of the patients reported high prevalence of symptoms, particularly lack of energy, difficulty sleeping, and worrying. The total number of symptoms increased during the treatment and returned to enrollment values at 6 months. This trend was dominated with physical symptoms. When we compared women with low (n = 33) versus high physical functioning (n = 49) at enrollment, low physical functioning was significantly associated with more symptoms and distress for the study period. Patients with low physical functioning were more likely to experience lack of energy (odds ratio [OR] = 8.33), feeling drowsy (OR = 4.17), feeling bloated (OR = 2.44), feeling sad (OR = 3.33), having pain (OR = 4.72), and worrying (OR = 2.50), and this remained stable throughout the observation period of 6 months. CONCLUSIONS: A high symptom burden was reported in this cohort of patients with ovarian cancer mainly treated with palliative intent. Low self-rated physical functioning was strongly associated with high symptom burden for the 6-month period. When chemotherapy is discussed with patients with ovarian cancer with low physical functioning, possible palliation benefits must be weighed against the added risk of long-term distressful symptoms that chemotherapy implies.

High-Sensitivity Troponin T vs I in Acute Coronary Syndrome: Prediction of Significant Coronary Lesions and Long-term Prognosis.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) T and I assays are established as crucial tools for the diagnosis of acute myocardial infarction (AMI), as they have been found superior to old troponin assays. However, eventual differences between the assays in prediction of significant coronary lesions and long-term prognosis in patients with acute coronary syndrome (ACS) have not been fully unraveled. METHODS: Serum concentrations of hs-cTnT (Roche), hs-cTnI (Abbott), and amino-terminal pro-B-type natriuretic peptide (NT-proBNP; Roche) in 390 non-ST-elevation (NSTE) ACS patients were evaluated in relation to significant coronary lesions on coronary angiography (defined as a stenosis >50% of the luminal diameter, with need for revascularization) and prognostic accuracy for cardiovascular mortality, all-cause mortality, as well as the composite end point of cardiovascular mortality and hospitalizations for AMI or heart failure. RESULTS: The mean (SD) follow-up was 2921 (168) days. Absolute hs-cTnI concentrations were significantly higher than the hs-cTnT concentrations. The relationship between analyzed biomarkers and significant coronary lesions on coronary angiography, as quantified by the area under the ROC curve (AUC), revealed no difference between hs-cTnT [AUC, 0.81; 95% CI, 0.77-0.86] and hs-cTnI (AUC, 0.81; 95% CI, 0.76-0.86; P = NS). NT-proBNP was superior to both hs-cTn assays regarding prognostic accuracy for both cardiovascular and all-cause mortality and for the composite end point during follow-up, also in multivariate analyses. CONCLUSIONS: The hs-cTnT and hs-cTnI assays displayed a similar ability to predict significant coronary lesions in NSTE-ACS patients. NT-proBNP was superior to both hs-cTn assays as a marker of long-term prognosis in this patient group.

Vitamin D deficiency in inflammatory bowel disease: prevalence and predictors in a Norwegian outpatient population.

BACKGROUND AND AIM: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD. METHODS: Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory. RESULTS: In total, 49% (200/408) of the patients had a 25-OH-D concentration <50 nmol/L, including 53% (122/230) of the Crohn's disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >100 mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.

Norwegian translation, and validation, of the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7).

INTRODUCTION AND HYPOTHESIS: The goal was to translate into Norwegian, and validate, short versions of the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) using a sample of women with symptomatic pelvic organ prolapse and pelvic floor dysfunction. METHODS: Modified European Organization for Research and Treatment of Cancer Guidelines were used for translation and cultural adaptation. Of 212 eligible Norwegian women who consented to participate, 205 completed the questionnaires, of whom 50 were retested after 1 - 3 weeks, and 76 were tested 6 months after surgery. Reliability, validity and responsiveness were evaluated. Additionally, interpretability, the smallest detectable change, the standard error of measurement, floor and ceiling effects, and the percentages of missing items are reported. RESULTS: Reliability ranged from 0.66 to 0.93 and intraclass correlation coefficients from 0.85 to 0.94. Both construct validity and responsiveness were found to be adequate. The responsiveness of the PFDI-20 was further supported by areas under the curve above 0.70. Estimates were lower for the PFIQ-7. The smallest detectable changes at the individual level were 15 - 21 % and 17 - 27 % for the PFDI-20 and PFIQ-7, respectively. The absolute values of the minimal important changes in the total scores were 48 and 47, respectively. No floor or ceiling effects were evident in the distributions of the PFDI-20 and PFIQ-7 total scores. CONCLUSIONS: The translated questionnaires provided adequate reliability, validity and good responsiveness to change. These short versions of the PFDI and PFIQ are robust measuring instruments that will enable symptom severity and health-related quality of life to be evaluated in the Norwegian context.

L1CAM as a prognostic marker in stage I endometrial cancer: a validation study.

BACKGROUND: L1 cell adhesion molecule (L1CAM) overexpression has been reported to be strongly associated with poor prognosis in early stage endometrial cancer (EC). We aimed at the validation of L1CAM as a marker of poor prognosis in an independent study population. METHODS: Patients with endometrioid EC FIGO stage I, were treated at Oslo University Hospital between 2005 and 2012. L1CAM expression was detected by immunohistochemistry with >10 % L1CAM staining defined as positive. Risks of relapse and death were estimated as hazard ratios (HRs) with 95 % confidence intervals (95 % CI). RESULTS: Of 450 patients, 388 (86 %) were evaluable for L1CAM expression and 35 (9 %) were L1CAM positive. After follow-up for a median time of 4.8 years (0.1-8.8), 33 (8 %) patients had recurred. 6/35 (17 %) L1CAM positive patients relapsed compared to 27/353 (8 %) L1CAM-negative patients. There were 7 (20 %) deaths in the L1CAM positive group, and 34 (10 %) in the negative group. In multivariate analysis, controlled for age and FIGO stage, L1CAM positivity was not significantly associated with the risk of relapse (HR 2.08, 95 % CI: 0.85-5.10, p = 0.11) or death of all-cause (HR 1.81, 95 % CI: 0.79-4.11, p = 0.16). In patients who were not treated with chemotherapy, L1CAM was significantly associated with risk of relapse (HR 2.9; 95 % CI: 1.08-7.56; p = 0.04). CONCLUSION: Our report confirms that L1CAM is associated with a more aggressive tumortype and more distant relapses. The overall recurrence rate in this population was low as were the absolute differences between L1CAM positive and negative patients. In this independent study sample, L1CAM failed to be a clinically relevant marker of poor prognosis in stage I endometrioid endometrial carcinoma.

Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma - A population-based cohort study.

BACKGROUND: Multimodality treatment (MMT) improves survival for patients with pancreatic ductal adenocarcinoma (PDAC). The surgery-first (SF) strategy is the most universally accepted approach. MATERIAL AND METHODS: Population-based retrospective cohort study of all cases of resectable PDAC from 2006 to 2012. Patients were planned for adjuvant chemotherapy (AC) with the Nordic 5-fluorouracil/leucovorin regimen. Reasons for and rates of failure to complete AC, postoperative major complications (PMC), and overall survival (OS) were analysed. RESULTS: Of 203 patients, 85 (41.9%) completed AC, 41 (20.2%) failed to complete AC, and 77 (37.9%) never initiated AC. Primary reasons for not initiating or completing AC were early disease progression (34.7%), postoperative complications/poor performance status (32.2%), and age > 75 years (24.6%). Median OS in the whole cohort was 17.0 months, and 20.0 months in patients who initiated AC. Median OS in patients who completed AC was higher than in patients who did not (25.0 months vs. 12.0 months, p < 0.001). PMC (n = 41) were associated with decreased initiation rate (p < 0.001) and completion rate (p = 0.007) of AC, and decreased median OS (11.0 months vs. 19.0 months, p = 0.028). Among patients with R1 resection, PMC again were associated with worse median OS (8.0 months vs. 16.0 months, p = 0.028). Multivariate analysis demonstrated that completion of MMT and tumour grade (G1/G2) were related to mortality rate (p < 0.001). Mortality risk for patients who completed AC was reduced also when adjusting for competing risk (SHR 0.426, p < 0.001). CONCLUSIONS: MMT completion is strongly associated with reduced mortality risk in patients with resectable PDAC undergoing the SF approach. Early disease progression and PMC/poor performance status preclude MMT completion in more than one third of the patients. These reasons for failure to complete MMT underscore the need for strategies to improve patient selection and reduce surgical morbidity in patients with resectable PDAC.

Immunological factors influencing clinical outcome in lung cancer patients after telomerase peptide vaccination.

We have previously reported two trials in non-small cell lung cancer (NSCLC) evaluating vaccine therapy with the telomerase peptide GV1001. The studies demonstrated considerable differences in survival among immune responders, highlighting that an immune response is not necessarily beneficial. In the present study, we conducted long-term clinical follow-up and investigated immunological factors hypothesized to influence clinical efficacy. Peripheral blood mononuclear cells from 33 NSCLC trial patients and 15 healthy donors were analyzed by flow cytometry for T regulatory cells (Tregs, CD4(+)CD25(+)CD127(low/-)FOXP3(+)) and two types of myeloid-derived suppressor cells (MDSCs, HLA-DR (low) CD14 (+) or Lin (-/lo) HLA-DR (-) CD33 (+) CD11b (+)). T cell cultures were analyzed for 17 cytokines. The results demonstrated that immune responders had increased overall survival (OS, p < 0.001) and progression-free survival (p = 0.003), compared to subjects without immunological response. The mean OS advantage was 54 versus 13 months. Six patients were still alive at the last clinical update, all belonging to the immune responders. No serious toxicity had developed (maximum observation 13 years). Most patients developed a polyfunctional cytokine profile, with high IFNγ/IL-4 and IFNγ/IL-10 ratios. Low Treg levels were associated with improved OS (p = 0.037) and a favorable cytokine profile, including higher IFNγ/IL-10 ratios. High CD33(+) MDSC levels were associated with poorer immune response rate (p = 0.005). The levels of CD14(+) MDSC were significantly higher in patients than in healthy controls (p = 0.012). We conclude that a randomized GV1001 trial in NSCLC is warranted. The findings suggest that Tregs and MDSCs are associated with a tolerogenic cytokine milieu and impaired clinical efficacy of vaccine responses.

Body mass index, diabetes and survival after diagnosis of endometrial cancer: A report from the HUNT-Survey.

OBJECTIVE: We studied the association of body mass index (BMI) and diabetes with all-cause death and endometrial cancer-specific death among women with endometrial cancer (EC). METHODS: Included were 337 women in the Health Surveys in North-Trøndelag, Norway who were followed from EC diagnosis to death or end of follow-up, 30th June 2012. Risks of death associated with BMI and diabetes were estimated as hazard ratios (HRs) with 95% confidence intervals (95% CI). The risks of EC-specific death were estimated as sub-HRs, after adjustment for competing causes of death. We also studied the risk of death associated with diabetes in women with BMI<25kg/m(2) and in women with BMI≥25kg/m(2). RESULTS: During the median follow-up time of 6.7years, 166 women (49.3%) died. Diabetes increased the risk of all-cause death (HR 2.14, 95% CI: 1.26-3.63) and endometrial cancer-specific death (SHR, 2.62, 95% CI: 1.07-6.43) after adjustment for age, histological type and stage of EC. BMI was not associated with risk of all-cause or EC-specific death. The increased risk of both all-cause death and EC specific death in diabetic women seemed to be more pronounced in women with BMI<25kg/m(2) (HR 6.35, 95% CI: 1.90-21.14) compared to women with BMI>25kg/m(2) (HR 1.80, 95% CI: 0.98-3.33). CONCLUSIONS: Diabetes, but not BMI, was associated with increased risk of all-cause death and death from EC. The increased risk of death associated with diabetes seemed to be most pronounced in women with BMI<25kg/m(2).

One-year protocol biopsies from ABO-incompatible renal allografts compared with a matched cohort of ABO-compatible allografts.

INTRODUCTION: Early acute antibody-mediated rejection (ABMR) occurs more frequently in ABO-incompatible (ABOi) than in ABO-compatible (ABOc) kidney transplantation. This could lead to increased inflammation/scarring in the ABOi grafts. Protocol biopsy data in ABOi kidney recipients are scarce. METHODS: A single-center retrospective matched cohort study was conducted. Eighty adult living donor (LD) renal transplant recipients without HLA donor-specific antibodies (DSA) transplanted between 2009 and 2012 were included; 20 ABOi and 60 ABOc controls matched for donor age and transplantation year. Protocol biopsies at one yr were scored according to the Banff classification. Three sums of scores were constructed: tubulointerstitial inflammation (t + i = 0 vs. >0), microvascular inflammation (g + ptc = 0 vs. >0), scarring/hyalinosis (ci + ct + cv + ah ≤ 1 vs. >1. Scores and presence of subclinical rejection (SCR) at one yr were compared. RESULTS: Protocol biopsy findings at one yr in the ABOi vs. ABOc matched control group were not statistically different: (t + i) > 0, 30% vs. 20%; (g + ptc) > 0, 5% vs. 8%; (ci + ct + cv + ah) > 1, 85% vs. 60%, respectively. No transplant glomerulopathy occurred. SCR rate at one yr was 30% vs. 18%, subclinical ABMR 5% vs. 7% (all with de novo HLA DSA). CONCLUSION: One-year protocol biopsies of ABOi and ABOc LD recipients do not differ in chronic changes, inflammation, or SCRs.

Risk matrix model for prediction of colectomy in a population-based study of ulcerative colitis patients (the IBSEN study).

OBJECTIVES: Identifying ulcerative colitis (UC) patients with increased risk of colectomy is essential for appropriate treatment. We aimed to develop a prediction model assessing the risk of having colectomy within the first 10 years after diagnosis. MATERIAL AND METHODS: A population-based inception cohort of UC patients diagnosed in south-eastern Norway between 1990 and 1994 has been followed for 10 years. Altogether 519 patients were recruited including 49 patients who were colectomized. Based on the best-fitted multivariate model, the probabilities of colectomy were computed for selected levels of baseline covariates, and the results arranged in a prediction matrix. The following risk factors at diagnosis were analyzed: age, smoking, sex, disease extent, weight loss and fever and need for systemic steroids. Biochemical markers included C-reactive protein (CRP, <30 or ≥30 mg/l); erythrocyte sedimentation rate (ESR, <30 or ≥30 mm/h) and hemoglobin (Hgb, <10.5 or ≥ 10.5 g/dL). RESULTS: Extent of disease, age (<40 years, ≥40 years), need for systemic steroids and CRP or ESR (<30 or ≥30) at diagnosis were independently associated with colectomy and were combined in a prediction matrix. The probabilities of colectomy during the follow-up period ranged from 2.6% to 40.1% depending on the combination of predictors at diagnosis. CONCLUSIONS: Our prediction model revealed significant differences in the probability of undergoing colectomy during a 10-years course of disease, which supports an early individualized treatment approach in UC.

Site-specific proportion cured models applied to cancer registry data.

PURPOSE: Proportion-cured models were applied to evaluate their applicability on data from a relatively small cancer registry and to assess the up-to-date survival level of major cancer types in Tyrol, Austria. METHODS: In total, the 25 most common types of cancer were analyzed with mixture cure models using the period approach for estimation of the proportion cured and median survival time of the fatal cases. RESULTS: For several of the cancer types, no estimates could be obtained. The models converged for 14 sites among females and for 15 among males. The highest estimate of the proportion cured was found for cervix cancer (74.0 %; 95 % CI 64.4-83.6) and the lowest for male pancreas cancer (4.6 %; 95 % CI 0.2-9.0). The highest median survival of the uncured was 2.7 years (95 % CI 1.2-6.0) for male larynx cancer and the lowest 0.3 years (95 % CI 0.1-0.6) for male acute myeloblastic leukemia (AML). CONCLUSIONS: The estimates seem reliable for stomach, colon, rectum, pancreas, lung, cervix, ovary, central nervous system/brain and AML cancer and among men also for head/neck, esophagus, liver and kidney cancer. Altogether, it is demonstrated that even data from a regional cancer registry covering a rather small region can be utilized to derive up-to-date survival estimates of various cancer types, enabling monitoring of the development and changes in cancer treatment. Moreover, potentially this methodology is advantageously employable in any situation where the number of cancer cases is limited.

Return to work and sick leave after radical prostatectomy: a prospective clinical study.

BACKGROUND: To evaluate work status at three months after radical prostatectomy (RP) in patients with prostate cancer (PCa) in relation to socio-demographics, urinary incontinence and bother, medical complications health-related quality of life (HRQOL) and surgical methods. To identify pre-RP available factors that can predict the duration of immediate post-RP sick leave. MATERIAL AND METHODS: This prospective questionnaire-based study included 264 men with PCa<65 years, who were active in the work force before RP. Urinary incontinence and bother were assessed using the Expanded Prostate Cancer Index Composite-50 (EPIC-50). HRQOL was measured using SF-12. Medical complications comprised self- reported new morbidities and re-hospitalizations within three months after RP. Patients' work status was defined as either "stable/improved" or "declined" at three months compared to work status at baseline. Duration of immediate post-RP sick leave was considered as prolonged when lasting >6 weeks. Associations were analyzed using logistic regression analyses. RESULTS: Almost 30% of the patients had declined work status three months after RP. Change of physical HRQOL was the only factor remaining significantly associated with declined work status in the multivariate analysis. Half of the patients had prolonged immediate sick leave. Having physically strenuous work was the strongest predictor for this outcome. CONCLUSIONS: Long periods of sick leave and reduced workforce participation after RP should be considered potential adverse effects of this treatment.

Comparing effects in regular practice of e-communication and Web-based self-management support among breast cancer patients: preliminary results from a randomized controlled trial.

BACKGROUND: While Web-based interventions have been shown to assist a wide range of patients successfully in managing their illness, few studies have examined the relative contribution of different Web-based components to improve outcomes. Further efficacy trials are needed to test the effects of Web support when offered as a part of routine care. OBJECTIVE: Our aim was to compare in regular care the effects of (1) an Internet-based patient provider communication service (IPPC), (2) WebChoice, a Web-based illness management system for breast cancer patients (IPPC included), and (3) usual care on symptom distress, anxiety, depression, (primary outcomes), and self-efficacy (secondary outcome). This study reports preliminary findings from 6 months' follow-up data in a 12-month trial. METHODS: We recruited 167 patients recently diagnosed with breast cancer and undergoing treatment from three Norwegian hospitals. The nurse-administered IPPC allowed patients to send secure e-messages to and receive e-messages from health care personnel at the hospital where they were treated. In addition to the IPPC, WebChoice contains components for symptom monitoring, tailored information and self-management support, a diary, and communication with other patients. A total of 20 care providers (11 nurses, 6 physicians, and 3 social workers) were trained to answer questions from patients. Outcomes were measured with questionnaires at study entry and at study months 2, 4, and 6. Linear mixed models for repeated measures were fitted to compare effects on outcomes over time. RESULTS: Patients were randomly assigned to the WebChoice group (n=64), the IPPC group (n=45), or the usual care group (n=58). Response rates to questionnaires were 73.7% (123/167) at 2 months, 65.9 (110/167) at 4 months, and 62.3% (104/167) at 6 months. Attrition was similar in all study groups. Among those with access to WebChoice, 64% (41/64) logged on more than once and 39% (25/64) sent e-messages to care providers. In the IPPC group, 40% (18/45) sent e-messages. Linear mixed models analyses revealed that the WebChoice group reported significantly lower symptom distress (mean difference 0.16, 95% CI 0.06-0.25, P=.001), anxiety (mean difference 0.79, 95% CI 0.09-1.49, P=.03), and depression (mean difference 0.79, 95% CI 0.09-1.49, P=.03) compared with the usual care group. The IPPC group reported significant lower depression scores compared with the usual care group (mean difference 0.69, 95% CI 0.05-1.32, P=.03), but no differences were observed for symptom distress or anxiety. No significant differences in self-efficacy were found among the study groups. CONCLUSIONS: In spite of practice variations and moderate use of the interventions, our results suggest that offering Web support as part of regular care can be a powerful tool to help patients manage their illness. Our finding that a nurse-administered IPPC alone can significantly reduce depression is particularly promising. However, the multicomponent intervention WebChoice had additional positive effects. TRIAL REGISTRATION: Clinicaltrials.gov:NCT00971009; http://clinicaltrials.gov/show/NCT00971009 (Archived by WebCite at http://www.webcitation.org/6USKezP0Y).