We use the additive risk model of Aalen (Aalen, 1980) as a model for the rate of a counting process. Rather than specifying the intensity, that is the instantaneous probability of an event conditional on the entire history of the relevant covariates and counting processes, we present a model for the rate function, i.e., the instantaneous probability of an event conditional on only a selected set of covariates. When the rate function for the counting process is of Aalen form we show that the usual Aalen estimator can be used and gives almost unbiased estimates. The usual martingale based variance estimator is incorrect and an alternative estimator should be used. We also consider the semi-parametric version of the Aalen model as a rate model (McKeague and Sasieni, 1994) and show that the standard errors that are computed based on an assumption of intensities are incorrect and give a different estimator. Finally, we introduce and implement a test-statistic for the hypothesis of a time-constant effect in both the non-parametric and semi-parametric model. A small simulation study was performed to evaluate the performance of the new estimator of the standard error.
: Biliary atresia (BA) is a leading cause of end-stage paediatric liver disease. Standard BA treatment is sequential surgery with an initial Kasai procedure (KP) followed by liver transplant (LT) for patients who progress to liver failure. A key determinant for the post-KP patient survival with their native liver is patient age at KP (older age, poorer outcome). Recently, European studies have reported that caseload experience influences prognosis with centres managing 3 cases per year). Overall patient, post-KP native liver, and LT survivals were compared between centres. Outcome parameters were reevaluated for patients grouped by the largest Canadian centre (>5 cases per year) and all other centres (
A new net survival method has been introduced by Pohar Perme et al. (2012 ) and recommended to substitute the relative survival methods in current use for evaluating population-based cancer survival.
The new method is based on the use of continuous follow-up time, and is unbiased only under non-informative censoring of the observed survival. However, the population-based cancer survival is often evaluated based on annually or monthly tabulated follow-up intervals. An empirical investigation based on data from the Finnish Cancer Registry was made into the practical importance of the censoring and the level of data tabulation. A systematic comparison was made against the earlier recommended Ederer II method of relative survival using the two currently available computer programs (Pohar Perme (2013)  and Dickman et al. (2013) ).
With exact or monthly tabulated data, the Pohar-Perme and the Ederer II methods give, on average, results that are at five years of follow-up less than 0.5% units and at 10 and 14 years 1-2% units apart from each other. The Pohar-Perme net survival estimator is prone to random variation and may result in biased estimates when exact follow-up times are not available or follow-up is incomplete. With annually tabulated follow-up times, estimates can deviate substantially from those based on more accurate observations, if the actuarial approach is not used.
At 5 years, both the methods perform well. In longer follow-up, the Pohar-Perme estimates should be interpreted with caution using error margins. The actuarial approach should be preferred, if data are annually tabulated.
Morbidity data on chronic viral hepatitis including cirrhotic stages of disease and lethality indexes in St. Petersburg are provided. The necessity of isolation in ICD- 10 and statistical accounting of chronic viral hepatitis diagnosis with outcome into cirrhosis (cirrhotic stage) is shown. During use of viral etiology liver cirrhosis diagnosis the disease is registered in the structure of liver diseases which does not allow to have data on unfavorable outcomes of chronic viral hepatitis and for complete morbidity accounting.
BACKGROUND: Previous studies of non-smoking individuals with severe alpha(1)-antitrypsin deficiency (PiZZ) have been sparse and included only a limited number of individuals, mostly identified by respiratory symptoms. The aim of this study was to estimate the prognosis of non-smoking PiZZ individuals and to analyse the most common causes of death by including a large number of individuals who had been identified by other means than respiratory symptoms. METHODS: The study included 568 non-smoking PiZZ subjects who were selected from the Swedish National AAT Deficiency Registry and followed up from 1991 to September 2007. Of these, 156 (27%) were identified by respiratory symptoms (respiratory cases) and 412 were identified by extrapulmonary symptoms or screening (non-respiratory cases). RESULTS: 93 subjects (16%) died during the follow-up period. The specific standardised mortality rate (SMR) for the whole study population was 2.32 (95% CI 1.87 to 2.83) with no significant difference between men and women. The SMR was 2.55 (95% CI 1.91 to 2.83) for the respiratory cases and 2.07 (95% CI 1.49 to 2.81) for the non-respiratory cases. Further calculation of SMR for subgroups in the non-respiratory cases showed that the SMR was 0.70 (95% CI 0.14 to 2.04) for individuals identified by family/population screening. Emphysema and liver cirrhosis were the most common causes of death (45% and 28%, respectively). Malignant transformation was found in 38% of the cases with cirrhosis. CONCLUSION: Non-smoking PiZZ individuals identified by screening do not have an increased mortality risk compared with the Swedish general population.
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) had been one of the malignancies with the highest reported increase of incidence in Sweden, but during the late 20-year period the incidence has been decreasing. The aims of our study were to state the impact of autopsy on diagnosis and to identify clinical characteristics in HCC. METHODOLOGY: This retrospective study was performed in Göteborg, Sweden and included all cases with a diagnosis of liver cancer from a period with a high autopsy frequency (1958-1979). The cases were reevaluated histopathologically and the autopsy records as well as the case files were scrutinized. RESULTS: The majority (63%) of the 530 biopsy verified cases of HCC were diagnosed unexpectedly at autopsy. Cirrhosis of the liver could be established in 71% of the cases, but was diagnosed or at least clinically suspected before the diagnosis of the tumor only in a minority (19%) of all HCC patients. At presentation, malaise (85%), weight loss (78%), anorexia (67%) and hepatomegaly (84%) were common. The median survival time from diagnosis was one month. In most cases (92%) the cause of death was either directly or indirectly related to HCC and/or underlying liver disease such as advanced tumor disease, hepatic failure and gastrointestinal bleeding. Spontaneous rupture of HCC was the cause of death in 17 cases (3%) CONCLUSIONS: In an unselected population in a low incidence area of HCC, most patients have clinically unknown cirrhosis of the liver and present with vague general paramalignant symptoms. HCC has an extremely poor prognosis. Since HCC, in a majority of cases, remains undiagnosed before death, the autopsy has great impact on the diagnosis. This should be considered in interpretation of results from epidemiological studies.
We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (
Recent studies have shown that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) may offer a survival advantage compared to monotherapy.
To study the effectiveness of combination therapy with RFA and TACE compared to that of TACE alone in a Scandinavian tertiary liver cancer center.
A retrospective study of the patients treated with combination therapy vis-à-vis TACE alone from June 2007 to November 2012 was performed. Eighteen patients were treated with a combination of RFA and TACE with an interval of 1-4 days between the treatments. For comparison, a group of 18 patients treated with TACE as monotherapy in the same time period was matched with the combination group by demographic data, tumor characteristics, biochemical and clinical parameters, and performance status (PS).
Each group consisted of 14 patients with cirrhosis and four without. There were no significant differences between the groups regarding age, gender, tumor characteristics, causes of cirrhosis, levels of bilirubin, creatinine, prothrombin time, Child Pugh score, or World Health Organization (WHO) performance status. The median survival of patients in the RFA?+?TACE combination group was 586 days compared to 296 days in the control group. The difference was not statistically significant (P?=?0.26). However, when we stratified the data for cirrhosis and WHO performance status, patients in the combination group had significantly better survival (P?=?0.024).
Combination therapy with RFA and TACE for unresectable HCC, compared to TACE alone, may offer a survival benefit for a selected group of patients with HCC.
The use of complementary and alternative medicine (CAM) is becoming more common, particularly among cancer patients. We sought to define the frequency of CAM use among general surgery, hepatobiliary and surgical oncology patients and to define some of the determinants of CAM use in patients with benign and malignant disease.
We asked all patients attending the clinics of 3 hepatobiliary/surgical oncology surgeons from 2002 to 2005 to voluntarily respond on first and subsequent visits to a questionnaire related to the use of CAM. We randomly selected patients for review.
We reviewed a total of 490 surveys from 357 patients. Overall CAM use was 27%. There was significantly more CAM use among cancer (34%) versus noncancer patients (21%; p = 0.008), and the use of CAM was more common in patients with unresectable cancer (51%) than resectable cancer (22%; p
Long-term use of ursodeoxycholic acid (UDCA) is the recommended therapy in primary biliary cirrhosis (PBC). The lifetime effectiveness and cost-effectiveness of UDCA in PBC have, however, not been assessed.
To estimate the health outcomes and lifetime costs of a Norwegian cohort of PBC patients on UDCA.
Norwegian PBC patients (n = 182) (90% females; mean age 56.3 ± 8.9 years; Mayo risk score 4.38) who were included in a 5-year open-label study of UDCA therapy were subsequently followed up for up to 11.5 years. The lifetime survival was estimated using a Weibull survival model. The survival benefit from UDCA was based on a randomised clinical trial from Canada, comparing the effect of non-UDCA and UDCA. Survival and costs of standard care vs. standard care plus UDCA were simulated in a Markov model with death and liver transplantation as major events, invoking transition of a patient's state in the model.
The gain in life expectancy for a PBC patient on UDCA compared with standard care was 2.24 years (1.19 years discounted). The lifetime treatment costs were EUR 151,403 and EUR 157,741 (EUR 102,912 and EUR 115,031 discounted) for patients with and without UDCA respectively. A probabilistic sensitivity analysis indicated an 82% probability that UDCA entails both greater life expectancy and lower costs than standard care.
The results of this study indicate that UDCA therapy is a dominant strategy as it confers reduced morbidity and mortality, as well as cost savings, compared with standard therapy.