Does the MOSES study provide sufficient evidence for Eprosartan against Nitrendipine?
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Acrylates↗
Biomedical subjects
Klaus Larsen
Publications and source records attributed to Klaus Larsen.
Prognosis in patients with cirrhosis and mild portal hypertension.
OBJECTIVE: Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. MATERIAL AND METHODS: Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. RESULTS: Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. CONCLUSIONS: The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.
Adult↗
[Stewed glands as hormone therapy].
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Concept Formation↗
Appropriate assessment of neighborhood effects on individual health: integrating random and fixed effects in multilevel logistic regression.
The logistic regression model is frequently used in epidemiologic studies, yielding odds ratio or relative risk interpretations. Inspired by the theory of linear normal models, the logistic regression model has been extended to allow for correlated responses by introducing random effects. However, the model does not inherit the interpretational features of the normal model. In this paper, the authors argue that the existing measures are unsatisfactory (and some of them are even improper) when quantifying results from multilevel logistic regression analyses. The authors suggest a measure of heterogeneity, the median odds ratio, that quantifies cluster heterogeneity and facilitates a direct comparison between covariate effects and the magnitude of heterogeneity in terms of well-known odds ratios. Quantifying cluster-level covariates in a meaningful way is a challenge in multilevel logistic regression. For this purpose, the authors propose an odds ratio measure, the interval odds ratio, that takes these difficulties into account. The authors demonstrate the two measures by investigating heterogeneity between neighborhoods and effects of neighborhood-level covariates in two examples--public physician visits and ischemic heart disease hospitalizations--using 1999 data on 11,312 men aged 45-85 years in Malmo, Sweden.
Aged↗
Histological characteristics and prognosis in patients with fatty liver.
OBJECTIVE: The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis. MATERIAL AND METHODS: A total of 417 patients had a liver biopsy performed, which showed fatty liver without inflammation. The population consisted of 170 non-alcoholic and 247 alcoholic fatty liver patients. The study cohort was linked through their unique personal identification number to The National Registry of Patients and the nationwide Registry of Causes of Death. RESULTS: Median follow-up time was 19.9 years in the non-alcoholic group and 12.8 years in the alcoholic group. Overall mortality in the non-alcoholic group was not related to morphological findings in the index liver biopsy. Mortality was significantly (p < 0.05) higher in alcoholic patients with severe steatosis. One non-alcoholic patient (0.6%) developed cirrhosis versus 54 alcoholic patients (22%) during the follow-up period. CONCLUSIONS: In patients with non-alcoholic fatty liver without inflammation, patients at risk for premature death cannot be identified by histological characteristics in the index liver biopsy. Patients with alcoholic fatty liver have a high risk for development of cirrhosis and increased mortality with the severity of steatosis in the index liver biopsy.
Adult↗
The cox proportional hazards model with a continuous latent variable measured by multiple binary indicators.
This article is motivated by the Women's Health and Aging Study, where information about physical functioning was recorded along with death information in a group of elderly women. The focus is on determining whether having difficulties in daily living tasks is accompanied by a higher mortality rate. To this end, a two-parameter logistic regression model is used for the modeling of binary questionnaire data assuming an underlying continuous latent variable, difficulty in daily living. The Cox model is used for the survival information, and the continuous latent variable is included as an explanatory variable along with other observed variables. Parameters are estimated by maximizing the likelihood for the joint distribution of the items and the time-to-event information. In addition to presenting a new statistical model, this article also illustrates the use of the model in a real data setting and addresses the more practical issues of model building, diagnostics, and parameter interpretation.
Aged↗
The incidence of asthma in young adults.
STUDY OBJECTIVES: Longitudinal data on adult asthma are sparse. The objectives of this study were to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period. DESIGN: From birth cohorts over the period 1953 to 1982 in The Danish Twin Registry, 19,349 subjects with no history of asthma, as determined by a questionnaire-based survey in 1994, answered a follow-up questionnaire in 2002. The subjects were regarded as incident asthma cases when answering "yes" to the question "Do you have, or have you ever had asthma?" in 2002, and "no" to the same question in 1994. RESULTS: A total of 838 cases (4.3%) of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and 6.4 per 1,000 person-years, respectively, among male and female subjects. For all ages, the probability of adult-onset asthma was greater for female subjects (odds ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in probability with increasing age. There was a positive association between increasing body mass index (BMI) and risk of adult-onset asthma applying to both sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were found between incident asthma and a history of hay fever (OR: male subjects, 4.2; female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects, 8.0; p < 0.001). CONCLUSIONS: There is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis.
Adolescent↗
Change in prevalence of asthma in Danish children and adolescents.
BACKGROUND: There is evidence suggesting that the prevalence of asthma has increased, especially in industrialized countries. OBJECTIVE: To investigate whether the prevalence of asthma in Danish children and adolescents has changed during the past 15 years. METHODS: Serial cross-sectional studies of 2 different random population samples of children aged 7 to 17 years, living in urban Copenhagen, Denmark, were performed 15 years apart. The first cohort was investigated in 1986 (n = 527) and the second in 2001 (n = 480). The same methods were applied at both occasions. Skin test reactivity was measured using standard techniques. Asthma was defined on the basis of questionnaire responses and was regarded as nonatopic (intrinsic) if no positive reactions were observed on the skin test and as atopic (extrinsic) if at least 1 positive reaction was noted. Current asthma was defined as symptoms within the preceding 12 months. RESULTS: The prevalence of current asthma increased from 5.3% in 1986 to 11.7% in 2001. This was primarily due to an increase in intrinsic asthma, which was 4.2-fold (1.5% to 6.4%), compared with extrinsic asthma, which increased only 1.4-fold (3.8% to 5.5%). The changes were more pronounced in girls. CONCLUSIONS: The prevalence of asthma has increased substantially during the past 15 years. The observed striking increase in intrinsic asthma suggests the possibility of a more heterogeneous disorder, involving more important factors than atopy. Furthermore, our findings suggest that asthma might be shifting toward female predominance in childhood.
Adolescent↗
Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients.
The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0.045)). However, the effect of tenofovir on HIV-RNA in the group of patients who had tenofovir added to a stable ART was limited, and the decrease in HIV-RNA was significantly higher in patients who had drugs other than tenofovir changed as well (p = 0.004 and p = 0.03 after 3 and 6 months, respectively). After initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti-retroviral drugs, to patients on a failing highly active antiretroviral drug regimen (HAART).
Adenine↗
Joint analysis of time-to-event and multiple binary indicators of latent classes.
Multiple categorical variables are commonly used in medical and epidemiological research to measure specific aspects of human health and functioning. To analyze such data, models have been developed considering these categorical variables as imperfect indicators of an individual's "true" status of health or functioning. In this article, the latent class regression model is used to model the relationship between covariates, a latent class variable (the unobserved status of health or functioning), and the observed indicators (e.g., variables from a questionnaire). The Cox model is extended to encompass a latent class variable as predictor of time-to-event, while using information about latent class membership available from multiple categorical indicators. The expectation-maximization (EM) algorithm is employed to obtain maximum likelihood estimates, and standard errors are calculated based on the profile likelihood, treating the nonparametric baseline hazard as a nuisance parameter. A sampling-based method for model checking is proposed. It allows for graphical investigation of the assumption of proportional hazards across latent classes. It may also be used for checking other model assumptions, such as no additional effect of the observed indicators given latent class. The usefulness of the model framework and the proposed techniques are illustrated in an analysis of data from the Women's Health and Aging Study concerning the effect of severe mobility disability on time-to-death for elderly women.
Aged↗
Maximum likelihood inference for multivariate frailty models using an automated Monte Carlo EM algorithm.
We present a maximum likelihood estimation procedure for the multivariate frailty model. The estimation is based on a Monte Carlo EM algorithm. The expectation step is approximated by averaging over random samples drawn from the posterior distribution of the frailties using rejection sampling. The maximization step reduces to a standard partial likelihood maximization. We also propose a simple rule based on the relative change in the parameter estimates to decide on sample size in each iteration and a stopping time for the algorithm. An important new concept is acquiring absolute convergence of the algorithm through sample size determination and an efficient sampling technique. The method is illustrated using a rat carcinogenesis dataset and data on vase lifetimes of cut roses. The estimation results are compared with approximate inference based on penalized partial likelihood using these two examples. Unlike the penalized partial likelihood estimation, the proposed full maximum likelihood estimation method accounts for all the uncertainty while estimating standard errors for the parameters.
Algorithms↗