Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study

BACKGROUND: The ABCB1 3435C-->T single-nucleotide polymorphism (SNP) or a three-SNP haplotype containing 3435C-->T has been implicated in multidrug resistance in epilepsy in three retrospective case-control studies, but a further three have failed to replicate the association. We aimed to determine the effect of the ABCB1 gene on epilepsy drug response, using a unique large cohort of epilepsy patients with prospectively measured seizure and drug response outcomes. METHODS: The ABCB1 3435C-->T polymorphism and three-SNP haplotype, plus a comprehensive set of tag SNPs across ABCB1 and adjacent ABCB4, were genotyped in a cohort of 503 epilepsy patients with prospectively measured seizure and drug response outcomes. Clinical, demographic, and genetic data were analysed. Treatment outcome was measured in terms of time to 12-month remission, time to first seizure, and time to drug withdrawal due to inadequate seizure control or side-effects. Randomly selected genome-wide HapMap SNPs (n=129) were genotyped in all patients for genomic control. FINDINGS: Number of seizures before treatment was the dominant feature predicting seizure outcome after starting antiepileptic drug therapy, measured by both time to first seizure (hazard ratio 1.34, 95% CI 1.21-1.49, p<0.0001) and time to 12-month remission (0.83, 0.73-0.94, p=0.003). There was no association of the ABCB1 3435C-->T polymorphism, the three-SNP haplotype, or any gene-wide tag SNP with time to first seizure after starting drug therapy, time to 12-month remission, or time to drug withdrawal due to unacceptable side-effects or to lack of seizure control. INTERPRETATION: We found no evidence that ABCB1 common variation influences either seizure or drug withdrawal outcomes after initiation of antiepileptic drug therapy.     

Sleep syncope: a prospective cohort study

Clinical Autonomic Research - Sleep syncope is defined as a form of vasovagal syncope which interrupts sleep. Long term follow-up has not been reported. Between 1999 and 2013 we diagnosed vasovagal...     

Dementia and Alzheimer disease incidence: a prospective cohort study

CONTEXT: Age-specific incidence rates for dementia and Alzheimer disease (AD) are important for research and clinical practice. Incidence estimates for the United States are few and vary with the population sampled and study design; we present data that will contribute to a consensus of these rates. OBJECTIVES: To provide age-specific incidence estimates for dementia and AD and to estimate the association of sex, educational level, and apolipoprotein E genotype with onset. DESIGN: Prospective cohort study; begun in 1994 with follow-up interviews every 2 years. SETTING: Members of community-based, large health maintenance organization with demographics consistent with the surrounding base population; diagnostic evaluation by university-based study clinicians. SUBJECTS: Random sample of subjects aged 65 years or older from the base population; dementia free, nonnursing home residents. Of 5422 who were eligible, 2581 were enrolled, and 2356 had at least 1 follow-up evaluation (10 591 person-years of observation). MAIN OUTCOME MEASURE: Dementia and Alzheimer disease diagnoses were based on standard criteria. Age-specific incidence rates were calculated using a person-years approach with Poisson distribution confidence intervals. Cox proportional hazards model analysis was used to examine other factors. RESULTS: Two hundred fifteen cases of dementia and 151 cases of AD were diagnosed. Incidence rates for dementia and AD increase across the 5-year age groups; AD rates rise from 2.8 per 1000 person-years (age group, 65-69 years) to 56.1 per 1000 person-years in the older than 90-year age group. The rates nearly triple from the 75-to-79-year and 80-to-84-year age groups, but the relative increase is much less thereafter. Sex was not associated with AD onset. Educational level (>15 years vs <12 years) was associated with a decreased risk of AD; however, the association was also dependent on the baseline cognitive screening test score. CONCLUSIONS: Our dementia and AD incidence rates are consistent with recent US and European cohort studies, providing clinicians and researchers new information concerning the reproducibility of incidence estimates across settings. Increased risk was associated with age and the apolipoprotein E genotype; also with a low baseline cognitive screening test score. Educational level was inversely associated with the risk of dementia and positively associated with the baseline cognitive test score; thus, detection of AD by the screening test could also be influenced by educational level.     

Depression and incident diabetic retinopathy: a prospective cohort study

Objective

This study examined whether depression is associated with a higher incidence of diabetic retinopathy among adults with type 2 diabetes after controlling for sociodemographic factors, health risk behaviors and clinical characteristics.

Method

This study included 2359 patients enrolled in Pathways Epidemiologic Follow-Up Study, a prospective cohort study investigating the impact of depression in primary care patients with type 2 diabetes. The predictor of interest was baseline severity of depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9). The outcome was incident diabetic retinopathy. Risk of diabetic retinopathy was assessed using logistic regression, and time to incident diabetic retinopathy was examined using Cox proportional hazard models.

Results

Over a 5-year follow-up period, severity of depression was associated with an increased risk of incident retinopathy [odds ratio =1.026; 95% confidence interval (CI) 1.002-1.051] as well as time to incident retinopathy (hazard ratio=1.025; 95% CI 1.009-1.041). The risk of incident diabetic retinopathy was estimated to increase by up to 15% for every significant increase in depressive symptoms severity (5-point increase on the PHQ-9 score).

Conclusion

Diabetic patients with comorbid depression have a significantly higher risk of developing diabetic retinopathy. Improving depression treatment in patients with diabetes could contribute to diabetic retinopathy prevention.     

Working conditions and psychotropic medication: a prospective cohort study

Purpose  

To examine whether work arrangements, physical working conditions and psychosocial working conditions are associated with subsequent mental health problems, measured by prescribed psychotropic drugs.     

Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction

BACKGROUND: Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown. This study, conducted between June 2001 and November 2002, evaluated the rate of smoking cessation and reduction in patients with schizophrenia (DSM-IV) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years. METHOD: Two years following a double-blind placebo-controlled trial of bupropion sustained release, 150 mg/day, added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia, subjects were interviewed, medical charts were reviewed, and carbon monoxide in expired air was measured. RESULTS: Seventeen of 18 subjects completed the follow-up assessment. More subjects were abstinent (22% [N = 4]) at the 2-year follow-up than were abstinent at the end of the trial (6% [N = 1]). Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years (4/7) than those who did not significantly reduce smoking during the trial (0/11) (chi(2) = 8.1, p <.005). Most subjects who achieved > or = 50% reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years. Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up (r = 0.60, p =.01). CONCLUSION: The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior. We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special populations is indicated.     

Doxepin as an adjunct to smoking cessation: a double-blind pilot study

In a double-blind study, 19 adults received bedtime doses of either 150 mg of doxepin hydrochloride (N = 9) or placebo (N = 10). After 3 weeks the subjects were instructed to stop smoking and continue taking medication for 4 additional weeks. Cessation was reported by all nine doxepin subjects 1 week after cessation and by seven doxepin subjects 9 weeks after cessation. One placebo subject reported cessation. Cotinine assays generally confirmed cessation but were subject to interpretation. Doxepin assays suggested that the precessation level was associated with cessation. Further studies with larger samples and extended follow-up are needed to determine the reliability of these results.     

A prospective study of smoking in young women and risk of later psychiatric hospitalization

Background: It is not known whether smoking is a risk factor for mental disorders. Aims: To investigate the prospective associations between cigarette smoking in pregnant women and a range of psychiatric hospital diagnoses. Method: Using data from the Copenhagen Perinatal Cohort, we followed a cohort of 7926 young women from 1959–61 to 2007, linking data on cigarette smoking with psychiatric admission diagnoses obtained from the Danish Psychiatric Central Register. The women were interviewed by a physician in 1959–61 when data was obtained on smoking and other health related variables. With adjustment for age, social class and psychopharmacological treatment at baseline, the effects of smoking on the risk of (hierarchically ordered) major categories of mental disorders were examined. Results: Significant positive associations were observed between number of cigarettes smoked and schizophrenia spectrum disorder, substance use-related disorder, a broad category of other non-psychotic disorders, and any psychiatric registration. For affective spectrum disorders, there was a significant, but non-linear association. Conclusion: Number of cigarettes smoked in young adulthood significantly predicted a range of psychiatric admission diagnoses and, for most diagnostic categories, evidence of a dose–response relationship was observed.     

Disability progression in multiple sclerosis: a Tunisian prospective cohort study

Neurological Sciences - Data regarding multiple sclerosis (MS) course in North Africans are scarce and mainly retrospective. To prospectively assess disability progression of multiple sclerosis in...     

Development of delirium: a prospective cohort study in a community hospital

BACKGROUND: Previous research on risk of delirium in acute hospital settings identified mainly patient variables (e.g., age) that are not amenable to intervention. The purpose of this study was to develop a model for new delirium in hospitalized older patients that included process of care and social variables. METHODS: A prospective cohort study was undertaken in a community hospital in Ontario, Canada. Research participants included 156 hospitalized patients age 65+ years and without delirium on admission who were admitted to a medical or surgical unit. The measures included daily appraisal of delirium using a standardized and validated tool, and assessment of patient, process of care, and social variables. RESULTS: Delirium developed in 28 of the 156 patients (17.9%). Older age and cognitive impairment were significant patient variables. Significant process of care variables included a high number of medications administered during hospitalization, surgery, a high number of procedures during early hospitalization (e.g., x-rays, blood tests), and intensive care treatment. CONCLUSIONS: Approximately one older patient in five developed delirium after admission to a medical or surgical unit. Risks not easily amenable to intervention included age, cognitive dysfunction, surgery, and intensive care requirements. Risk factors that are potentially modifiable included number of medications and number of procedures. Future research might focus on the efficacy of such intervention to reduce new-onset delirium in acute hospital settings.     

Continuity of care and clinical outcome: a prospective cohort study

  Background: Continuity of care is a central objective of community psychiatric services, but there is no consensus about its measurement. Aims: We developed measures of continuity of care suitable for routine use, and measured continuity and individual patient outcome over a period in which community services were developing. Method: One hundred patients with severe mental illness receiving continuing care from two sectorised services were sampled and interviewed. Data were collected concerning their care over 20 months prior to interview. After 20 months prospective follow-up, they were re-interviewed. Continuity was defined as: perceived accessibility of services and knowledge about them, the number of keyworkers in a defined period of time, and the proportion of time out of contact with services. Results: Continuity of care improved significantly on all measures over the period of the study. Individual patient outcome also improved, but in multiple regression models including clinical and demographic variables, measures of continuity were not significant predictors of outcome. Continuity was similar for white and non-white patients. Conclusion: Simple measures of continuity are useful in evaluating changes in the process of care, but they are not straightforwardly related to individual outcome. Accepted: 16 March 2000