Long-term survivor mixture model with random effects: application to a multi-centre clinical trial of carcinoma

A mixture model incorporating long-term survivors has been adopted in the field of biostatistics where some individuals may never experience the failure event under study. The surviving fractions may be considered as cured. In most applications, the survival times are assumed to be independent. However, when the survival data are obtained from a multi-centre clinical trial, it is conceived that the environ mental conditions and facilities shared within clinic affects the proportion cured as well as the failure risk for the uncured individuals. It necessitates a long-term survivor mixture model with random effects. In this paper, the long-term survivor mixture model is extended for the analysis of multivariate failure time data using the generalized linear mixed model (GLMM) approach. The proposed model is applied to analyse a numerical data set from a multi-centre clinical trial of carcinoma as an illustration. Some simulation experiments are performed to assess the applicability of the model based on the average biases of the estimates formed. Copyright (C) 2001 John Wiley & Sons, Ltd.

Fossil trees in ancient fluvial channel deposits: evidence of seasonal and longer-term climatic variability

It has been established that large numbers of certain trees can survive in the beds of rivers of northeastern Australia where a strongly seasonal distribution of precipitation causes extreme variations in flow on both a yearly and longer-term basis. In these rivers, minimal flow occurs throughout much of any year and for periods of up to several years, allowing the trees to become established and to adapt their form in order to facilitate their survival in environments that experience periodic inundation by fast-flowing, debris-laden water. Such trees (notably paperbark trees of the angiosperm genus Melaleuca) adopt a reclined to prostrate, downstream-trailing habit, have a multiple-stemmed form, modified crown with weeping foliage, development of thick, spongy bark, anchoring of roots into firm to lithified substrates beneath the channel floor, root regeneration, and develop in flow-parallel, linear groves. Individuals from within flow-parallel, linear groves are preserved in situ within the alluvial deposit of the river following burial and death. Four examples of in situ tree fossils within alluvial channel deposits in the Permian of eastern Australia demonstrate that specialised riverbed plant communities also existed at times in the geological past. These examples, from the Lower Permian Carmila Beds, Upper Permian Moranbah Coal Measures and Baralaba Coal Measures of central Queensland and the Upper Permian Newcastle Coal Measures of central New South Wales, show several of the characteristics of trees described from modern rivers in northeastern Australia, including preservation in closely-spaced groups. These properties, together with independent sedimentological evidence, suggest that the Permian trees were adapted to an environment affected by highly variable runoff, albeit in a more temperate climatic situation than the modem Australian examples. It is proposed that occurrences of fossil trees preserved in situ within alluvial channel deposits may be diagnostic of environments controlled by seasonal and longer-term variability in fluvial runoff, and hence may have value in interpreting aspects of palaeoclimate from ancient alluvial successions. (C) 2001 Elsevier Science B.V. All rights reserved.

Long-term risk stratification for survivors of acute coronary syndromes - Results from the long-term intervention with pravastatin in ischemic disease (LIPID) study

OBJECTIVES We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% fur those assigned placebo. CONCLUSIONS Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy. CT Am Coil Cardiol 2001;38:56-63) (C) 2001 by the American College of Cardiology.

Long-Term Effects of Specific Stabilizing Exercises for First-Episode Low Back Pain

Study Design. A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups. Objective. To report a specific exercise intervention’s long-term effects on recurrence rates in acute, first-episode low back pain patients. Summary of Background Data. The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term. Methods. Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients. Results. Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P , 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P , 0.01). Conclusion. Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone. [Key Words: multifidus, low back pain, rehabilitation]