Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Longchain-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. Objective: To determine whether -3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis. Design: Randomized, d ouble-blind, p lacebocontrolled trial conducted between 2004 and 2007. Setting: Psychosis detection unit of a large public hospital in Vienna, Austria. Participants: Eighty-one individuals at ultra-high risk of psychotic disorder. Interventions: A 12-week intervention period of 1.2g/d -3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months. Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of -6 to -3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition. Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study’s end (12 months), 2 of 41 individuals (4.9%) in the -3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to fullthreshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). -3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P=.01), negative symptoms (P=.02), and general symptoms (P=.01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups. Conclusions: Long-chain-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration: clinicaltrials.gov Identifier: NCT00396643

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Long-chain ω-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial

Mixed models have become very popular for the analysis of longitudinal data, partly because they are flexible and widely applicable, partly also because many commercially available software packages offer procedures to fit them. They assume that measurements from a single subject share a set of latent, unobserved, random effects which are used to generate an association structure between the repeated measurements. In this chapter, we give an overview of frequently used mixed models for continuous as well as discrete longitudinal data, with emphasis on model formulation and parameter interpretation. The fact that the latent structures generate associations implies that mixed models are also extremely convenient for the joint analysis of longitudinal data with other outcomes such as dropout time or some time-to-event outcome, or for the analysis of multiple longitudinally measured outcomes. All models will be extensively illustrated with the analysis of real data.

/pdf/random-effects-models-for-longitudinal-data-1jcr7vk0zp.pdf

Random Effects Models for Longitudinal Data

Opportunities and challenges in developing risk prediction models with electronic health records data: a systematic review

An introduction to event history analysis via multi-state models is given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.

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Multi-state models for event history analysis

This paper formulates a class of models for the joint behaviour of a sequence of longitudinal measurements and an associated sequence of event times, including single-event survival data. This class includes and extends a number of specific models which have been proposed recently, and, in the absence of association, reduces to separate models for the measurements and events based, respectively, on a normal linear model with correlated errors and a semi-parametric proportional hazards or intensity model with frailty. Special cases of the model class are discussed in detail and an estimation procedure which allows the two components to be linked through a latent stochastic process is described. Methods are illustrated using results from a clinical trial into the treatment of schizophrenia.

/pdf/joint-modelling-of-longitudinal-measurements-and-event-time-4so99fccfs.pdf

Joint modelling of longitudinal measurements and event time data.

Methods for the combined analysis of survival time and longitudinal biomarker data have been developed in recent years, with most emphasis on modelling and estimation. This paper focuses on the use of longitudinal marker trajectories as individual-level surrogates for survival. A score test for association which requires only standard methods for implementation is derived for the initial identification of candidate biomarkers. Methods for assessing efficacy of markers are discussed and a measure contrasting conditional and marginal distributions is proposed. An application using prothrombin index as biomarker for survival of liver cirrhosis patients is included.

/pdf/identification-and-efficacy-of-longitudinal-markers-for-3srwvz1opc.pdf

Identification and efficacy of longitudinal markers for survival

Nous presentons une gamme de procedures graphiques informelles visant au diagnostic des modeles de donnees jointes longitudinales et de date d'abandon. Un cadre d'effets aleatoires est envisage pour des reponses gaussiennes et des temps d'abandon a risques proportionnels. Nous examinons une evaluation preliminaire des classes d'abandon basee sur les residus, apres une analyse longitudinale classique ne prenant pas en compte les abandons informatifs. Nous discutons les proprietes des residus conditionnellement a l'information d'abandon, et nous considerons l'influence des cas. Les methodes proposees ne necessitent pas de methodes intensives de calcul au-dela de celles utilisees pour ajuster le modele propose. Un essai longitudinal sur le traitement de la schizophrenie est utilise pour illustrer nos suggestions.

Angela Dobson

Papers

Joint modelling of longitudinal measurements and event time data.

Identification and efficacy of longitudinal markers for survival

Diagnostics for joint longitudinal and dropout time modeling.