Inference on latent factor models for informative censoring.

This work discusses the problem of informative censoring in survival studies. A joint model for the time to event and the time to censoring is presented. Their hazard functions include a latent factor in order to identify this joint model without sacrificing the flexibility of the parametric specification. Furthermore, a fully Bayesian formulation with a semi-parametric proportional hazard function is provided. Similar latent variable models have been described in literature, but here the emphasis is on the performance of the inferential task of the resulting mixture model with unknown number of components. The posterior distribution of the parameters is estimated using Hamiltonian Monte Carlo methods implemented in Stan. Simulation studies are provided to study its performance and the methodology is implemented for the analysis of the ACTG175 clinical trial dataset yielding a better fit. The results are also compared to the non-informative censoring case to show that ignoring informative censoring may lead to serious biases.

A preference-based item response theory model to measure health: concept and mathematics of the multi-attribute preference response model.

BACKGROUND: A new patient-reported health measurement model has been developed to quantify descriptions of health states. Known as the multi-attribute preference response (MAPR) model, it is based on item response theory. The response task in the MAPR is for a patient to judge whether hypothetical health-state descriptions are better or worse than his/her own health status. METHODS: In its most simple form MAPR is a Rasch model where for each respondent on the same unidimensional health scale values are estimated of their own health status and values of the hypothetical comparator health states. These values reflect the quality or severity of the health states. Alternatively, the respondents are offered health-state descriptions that are based on a classification system (e.g., multi-attribute) with a fixed number of health attributes, each with a limited number of levels. In the latter variant, the weights of the levels of the attributes in the descriptive system, which represents the range of the health states, are estimated. The results of a small empirical study are presented to illustrate the procedures of the MAPR model and possible extensions of the model are discussed. RESULTS: The small study that we conducted to illustrate the procedure and results of our proposed method to measure the quality of health states and patients' own health status showed confirming results. CONCLUSIONS: This paper introduces the typical MAPR model and shows how it extends the basic Rasch model with a regression function for the attributes of the health-state classification system.

Persistent Low Rates of Treatment of Metabolic Risk Factors in People With Psychotic Disorders: A PHAMOUS Study.

OBJECTIVE: People with psychotic disorders have an increased metabolic risk and a shortened life expectancy compared to the general population. Two large studies showed that metabolic disorders were untreated in a majority of the patients. Since then, guidelines have urged monitoring of metabolic health. This study examined the course of metabolic disorders over time in people with psychotic disorders and investigated current treatment rates. METHODS: A total of 1,259 patients with psychotic disorders, as defined by the DSM-IV, from 4 Dutch mental health institutions participated in 3 yearly assessments of the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) between 2006 and 2014. Patients' metabolic parameters were measured, and the use of pharmacologic treatment for hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg), dyslipidemia (5% ≤ Systematic COronary Risk Evaluation [SCORE] risk < 10% and low-density lipoprotein [LDL] cholesterol level ≥ 2.5 mmol/L or SCORE risk ≥ 10% and LDL cholesterol level ≥ 1.8 mmol/L and/or triglycerides ≥ 2.3 mmol/L), and hyperglycemia (hemoglobin A1c concentration > 7% and/or fasting glucose concentration ≥ 7.2 mmol/L) was recorded. RESULTS: Prevalence of the metabolic syndrome, as defined by the National Cholesterol Education Program criteria, was > 50% at each assessment. On the basis of the European Society of Cardiology guidelines, pharmacotherapy for metabolic disorders was recommended for 52%-59% of the patients at each assessment. Treatment rates with antihypertensive (from 31% to 38%, P < .001) pharmacotherapy increased throughout the assessments. However, half of the patients were not treated for their metabolic risk factors while being monitored for 3 years or longer. Older patients were more likely to receive treatment, and patients who received treatment had lower blood pressure and lower cholesterol and triglyceride concentrations than patients not receiving the recommended treatment. CONCLUSIONS: Metabolic risk factors are still seriously undertreated in people with psychotic disorders. Better adherence to and better implementation of guidelines about monitoring and treating metabolic disorders in psychiatry are crucial.

A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome: A comparison of different designs.

This paper compares the power of the parallel group design, the matched-pairs design, and several options for the stepped wedge and delayed start designs for testing a possible effect of intranasal insulin with respect to placebo on developmental growth of children with a rare disorder like Phelan-McDermid syndrome. A subject-specific linear mixed effects model for the primary outcome developmental age in a longitudinal setting with five time points was assumed. Monte Carlo simulation studies with small sample sizes were applied since the rare disorder prohibits large trials. The stepped wedge designs, which were initially preferred for ethical reasons, appear to be competitive in power to other designs and were in some settings even the best. The assumed statistical model also demonstrates that all of the designs can be viewed as a stepped wedge or delayed treatment design. Our results show that the stepped wedge design is an appropriate alternative for randomized controlled trials on developmental growth with small numbers of participants under the formulated statistical conditions.

Cannabis use in people with severe mental illness: The association with physical and mental health--a cohort study. A Pharmacotherapy Monitoring and Outcome Survey study.

OBJECTIVE: In the general population cannabis use is associated with better cardiometabolic outcomes. Patients with severe mental illness frequently use cannabis, but also present increased cardiometabolic risk factors. We explore the association between cannabis use and cardiometabolic risk factors in patients with severe mental illness. METHOD: A total of 3169 patients with severe mental illness from a Dutch cohort were included in the study. The association of cannabis use with body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, glycated hemoglobin and Positive and Negative Syndrome Scale was examined with separate univariate AN(C)OVA. Changes in metabolic risk factors and Positive and Negative Syndrome Scale were examined after a follow-up interval of 9-24 months, for patients who continued, discontinued, started or were never using cannabis between the two assessments. RESULTS: Cannabis users at baseline had lower body mass index, smaller waist circumference, lower diastolic blood pressure, and more severe psychotic symptoms than non-users. Patients who discontinued their cannabis use after the first assessment had a greater increase in body mass index, waist circumference, diastolic blood pressure and triglyceride concentrations than other patients, and the severity of their psychotic symptoms had decreased more compared to continued users and non-users. CONCLUSION: Extra attention should be paid to the monitoring and treatment of metabolic parameters in patients who discontinue their cannabis use.

Effectiveness and cost-effectiveness of cognitive adaptation training as a nursing intervention in long-term residential patients with severe mental illness: study protocol for a randomized controlled trial.

BACKGROUND: Despite the well-known importance of cognitive deficits for everyday functioning in patients with severe mental illness (SMI), evidence-based interventions directed at these problems are especially scarce for SMI patients in long-term clinical facilities. Cognitive adaptation Training (CAT) is a compensatory approach that aims at creating new routines in patients' living environments through the use of environmental supports. Previous studies on CAT showed that CAT is effective in improving everyday functioning in outpatients with schizophrenia. The aim of this study is to evaluate the effect of CAT as a nursing intervention in SMI patients who reside in long-term clinical facilities. METHODS/DESIGN: This is a multicenter cluster randomized controlled trial comparing CAT (intervention group) as a nursing intervention to treatment as usual (control group). The primary goal is to evaluate the effectiveness of CAT on everyday functioning. Secondary outcomes are quality of life, empowerment and apathy. Further, an economic evaluation will be performed. The study has a duration of one year, with four follow-up assessments at 15, 18, 21 and 24 months for the intervention group. DISCUSSION: There is a need for evidence-based interventions that contribute to the improvement of the functional recovery of long-term residential patients. If our hypotheses are confirmed, it may be recommended to include CAT in the guidelines for SMI care and to implement the method in standardized care. TRIAL REGISTRATION: Nederlands Trial Register (identifier: NTR3308 ). Date registered: 12 February 2012.

Active encouragement of older women with urinary incontinence in primary care to undergo diagnosis and treatment: a matched-pair cluster randomized controlled trial.

OBJECTIVES: The URINO trial investigated the effect of offering treatment to older women with urinary incontinence in the general population, who had not sought help on their own initiative. STUDY DESIGN: In a cluster randomized trial, 14 general practitioners were matched into pairs and randomly allocated to an intervention or a control group. Women aged ≥ 55 years registered in the participating practices were asked about urinary incontinence via a postal questionnaire. Patients in the intervention group were assessed and treated whereas patients in the control group received standard care. MAIN OUTCOME MEASURES: Primary outcome was improvement (yes or no) of the severity of symptoms at 12-month follow-up measured with the Incontinence Severity Index. Secondary outcomes were the number of incontinence episodes per day and quality of life. The primary analysis was on an intention-to-treat basis with multiple imputation of missing data. A logistic regression model with correction for cluster randomization was fitted to estimate odds ratios (ORs). RESULTS: At 12 months, the severity of symptoms had improved in more patients in the intervention group (n166) than in the controls (n184) (OR 1.9; 95% CI 1.1-3.3). Also, the number of patients with fewer episodes of incontinence had increased (OR 2.5; 95% CI 1.5-4.1). No between-group differences in changes in quality of life were apparent (p0.14). CONCLUSIONS: It is recommended to encourage women in the general population aged ≥ 55 years with urinary incontinence to undergo diagnosis and treatment.

Health-related quality of life in epidermolysis bullosa: Validation of the Dutch QOLEB questionnaire and assessment in the Dutch population.

Defining the health-related quality of life (HRQoL) in patients suffering from the heritable blistering disease epidermolysis bullosa (EB) is important in assessing the efficacy of new treatments. The quality of life in EB questionnaire (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL in Dutch EB patients. The QOLEB was translated to Dutch according to protocol. Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had excellant correlation with the Skindex-29 (ρs = 0.86), good correlation with the SF-36 physical score (ρs = -0.75), and moderate correlation with the SF-36 mental score (ρs = -0.43). The discriminative validity between the 4 different EB subtypes was significant (p = 0.002). The internal consistency was excellent (α = 0.905), and the test-retest reliability strong (ρs = 0.88). In conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment of the HRQoL in adult EB patients.

Causal inference algorithms can be useful in life course epidemiology.

OBJECTIVES: Life course epidemiology attempts to unravel causal relationships between variables observed over time. Causal relationships can be represented as directed acyclic graphs. This article explains the theoretical concepts of the search algorithms used for finding such representations, discusses various types of such algorithms, and exemplifies their use in the context of obesity and insulin resistance. STUDY DESIGN AND SETTING: We investigated possible causal relations between gender, birth weight, waist circumference, and blood glucose level of 4,081 adult participants of the Prevention of REnal and Vascular ENd-stage Disease study. The latter two variables were measured at three time points at intervals of about 3 years. RESULTS: We present the resulting causal graphs, estimate parameters of the corresponding structural equation models, and discuss usefulness and limitations of this methodology. CONCLUSION: As an exploratory method, causal graphs and the associated theory can help construct possible causal models underlying observational data. In this way, the causal search algorithms provide a valuable statistical tool for life course epidemiological research.