Racial discrimination, binge drinking, and negative drinking consequences among black college students: serial mediation by depressive symptoms and coping motives.

Objectives: Experiences of racial discrimination have been associated with diverse negative health outcomes among racial minorities. However, extant findings of the association between racial discrimination and alcohol behaviors among Black college students are mixed. The current study examined mediating roles of depressive symptoms and coping drinking motives in the association of perceived racial discrimination with binge drinking and negative drinking consequences. Design: Data were obtained from a cross-sectional study of Black college students attending a predominantly White institution in the northeastern US (N = 251, 66% female, mean age = 20 years). Results: Results from path analysis showed that, when potential mediators were not considered, perceived racial discrimination was positively associated with negative drinking consequences but not frequency of binge drinking. Serial multiple mediation analysis showed that depressive symptoms and in turn coping drinking motives partially mediated the associations of perceived racial discrimination with both binge drinking frequency and negative drinking consequences (after controlling for sex, age, and negative life events). Conclusions: Perceived racial discrimination is directly associated with experiences of alcohol-related problems, but not binge drinking behaviors among Black college students. Affective responses to perceived racial discrimination experiences and drinking to cope may serve as risk mechanisms for alcohol-related problems in this population. Implications for prevention and intervention efforts are discussed.

Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

BACKGROUND: The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. METHOD: A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. RESULTS: Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. CONCLUSIONS: These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

Knowledge gaps and uncertainties about epilepsy: findings from an ethnographic study in China.

Epilepsy represents one of the major brain disorders worldwide. In China, research into how much people with epilepsy know about their condition appears limited. Drawing on data collected as part of a large ethnographic study, we present the experiences and views of Chinese people with epilepsy and their family members, to identify knowledge gaps and uncertainties about epilepsy within selected urban and rural communities. We also examine how respondents' demographic characteristics influence their knowledge, understanding, and beliefs about epilepsy. We found knowledge and understanding of epilepsy to be uneven and context specific. Hereditary factors were most frequently cited as a potential cause, although their impact remained unclear. Western medicalization of epilepsy appears less evident in the reports of rural informants, where traditional beliefs continue to shape definitions and treatment. Societal differences within these communities set boundaries on knowledge acquisition. Plotted against these differences, we suggest strategies for proposed educational/psychosocial intervention programs.

A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial.

OBJECTIVES: To compare clinicians' choice of one of the standard epilepsy drug treatments (carbamazepine or valproate) versus appropriate comparator new drugs. DESIGN: A clinical trial comprising two arms, one comparing new drugs in carbamazepine and the other with valproate. SETTING: A multicentre study recruiting patients with epilepsy from hospital outpatient clinics. PARTICIPANTS: Patients with an adequately documented history of two or more clinically definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option. INTERVENTIONS: Arm A was carbamazepine (CBZ) versus gabapentin (GBP) versus lamotrigine (LTG) versus oxcarbazepine (OXC) versus topiramate (TPM). Arm B valproate (VPS) versus LTG versus TPM. MAIN OUTCOME MEASURES: Time to treatment failure (withdrawal of the randomised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two) and time to achieve a 12-month remission of seizures. Time from randomisation to first seizure, 24-month remission of seizures, incidence of clinically important adverse events, quality of life (QoL) outcomes and health economic outcomes were also considered. RESULTS: Arm A recruited 1721 patients (88% with symptomatic or cryptogenic partial epilepsy and 10% with unclassified epilepsy). Arm B recruited 716 patients (63% with idiopathic generalised epilepsy and 25% with unclassified epilepsy). In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC. Some 12% and 8% fewer patients experienced treatment failure on LTG than CBZ, the standard drug, at 1 and 2 years after randomisation, respectively. The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinically inferior to CBZ for measures of its efficacy. No consistent differences in QoL outcomes were found between treatment groups. Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality-adjusted life-year gained. In Arm B for time to treatment failure, VPS, the standard drug, was preferred to both TPM and LTG, as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission. QoL assessments did not show any between-treatment differences. The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy, although there is a suggestion that TPM is a cost-effective alternative to VPS. CONCLUSIONS: The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing standard drug treatment, CBZ, for patients diagnosed as having partial seizures. For patients with idiopathic generalised epilepsy or difficult to classify epilepsy, VPS remains the clinically most effective drug, although TPM may be a cost-effective alternative for some patients. Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy (levetiracetam, zonisamide and pregabalin), therefore these drugs should be compared in a similarly designed trial.

Self-management education for adults with epilepsy.

BACKGROUND: Self-management education has been shown to improve the quality of life of people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for adults with epilepsy. SEARCH STRATEGY: We searched MEDLINE (Ovid) (1966 to April 2005), EMBASE (Ovid) (1980 to April 2005), CINAHL (Dialog) (1980 to April 2005), PsycINFO (Dialog) (1887 to April 2005), and the Cochrane Epilepsy Group's Specialised Register (April 2005). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. We did not impose any language restriction. We re-ran the searches in February 2007 and added the identified references to the 'Studies awaiting assessment' table. SELECTION CRITERIA: Randomised trials of self-management education programmes for adults with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Two trials evaluated the effect of self-management education for adults with epilepsy, neither of which assessed as being of high quality. In total, 483 adults with epilepsy were randomised. Both trials showed improvements in seizure frequency and other outcomes, such as knowledge. However, we were not able to estimate a summary effect for seizure frequency due to a lack of data. AUTHORS' CONCLUSIONS: Self-management education programmes, based on increasing understanding through psychosocial methods, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency. It is, however, not clear how effective self-management programmes of epilepsy would be in a more general population of adults with epilepsy, as both trials had higher proportions of people with partial seizures than would be expected in a community sample.

Self-management education for children with epilepsy.

BACKGROUND: Self-management education has been shown to improve the quality of life of children and young people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in children and young people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for children and young people with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialised Register (April 2007), MEDLINE (Ovid) (1966 to February 2007), EMBASE (Ovid) (1980 to February 2007), CINAHL (Dialog) (1980 to February 2007), and PsycINFO (Dialog) (1887 to February 2007). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. No language restriction was imposed. SELECTION CRITERIA: Randomised trials of self-management education programmes for children or young people with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Only one trial involving 167 children was identified that evaluated the effect of a child-centred model of training for the self-management of two chronic illnesses, asthma and epilepsy. The trial was not assessed as being of high quality and the methods used to analyse and report the data did not enable us to precisely determine the effect of the intervention. However, improvements were seen in seizure frequency and other outcomes, such as knowledge and behaviour. AUTHORS' CONCLUSIONS: Self-management education programmes that deliver a child-centred model of training, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency in children and young people with epilepsy. However, based on the evidence reviewed, we are not able to determine how effective it is, or what the key components of the programme should be.

Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial.

BACKGROUND: The relative risks and benefits of starting or withholding antiepileptic drug treatment in patients with few or infrequent seizures are unclear. We sought to compare policies of immediate versus deferred treatment in such patients and to assess the effects of these policies on short-term recurrence and long-term outcomes. METHODS: We undertook an unmasked, multicentre, randomised study of immediate and deferred antiepileptic drug treatment in 1847 patients with single seizures and early epilepsy. Outcomes comprised time to first, second, and fifth seizures; time to 2-year remission; no seizures between years 1 and 3 and between years 3 and 5 after randomisation; and quality of life. Analysis was by intention to treat. FINDINGS: 404 patients invited to join the trial did not consent to randomisation; 722 were subsequently assigned immediate treatment with antiepileptic drugs and 721 were assigned deferred treatment. Immediate treatment increased time to first seizure (hazard ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2-year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in the immediate treatment group and 77% of those in the deferred treatment group were seizure free between 3 and 5 years after randomisation (difference -0.2% [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality of life outcomes or serious complications. INTERPRETATION: Immediate antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2 years, but does not affect long-term remission in individuals with single or infrequent seizures.

Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.

The mechanisms underlying bipolar disorder (BD) and the associated medical burden are unclear. Damage generated by oxidation of nucleosides may be implicated in BD pathophysiology; however, evidence from in vivo studies is limited and the extent of state-related alterations is unclear. This prospective study investigated for we believe the first time the damage generated by oxidation of DNA and RNA strictly in patients with type I BD in a manic or mixed state and subsequent episodes and remission compared with healthy control subjects. Urinary excretion of 8-oxo-deoxyguanosine (8-oxodG) and 8-oxo-guanosine (8-oxoGuo), valid markers of whole-body DNA and RNA damage by oxidation, respectively, was measured in 54 patients with BD I and in 35 healthy control subjects using a modified ultraperformance liquid chromatography and mass spectrometry assay. Repeated measurements were evaluated in various affective phases during a 6- to 12-month period and compared with repeated measurements in healthy control subjects. Independent of lifestyle and demographic variables, a 34% (P<0.0001) increase in RNA damage by oxidation across all affective states, including euthymia, was found in patients with BD I compared with healthy control subjects. Increases in DNA and RNA oxidation of 18% (P<0.0001) and 8% (P=0.02), respectively, were found in manic/hypomanic states compared with euthymia, and levels of 8-oxodG decreased 15% (P<0.0001) from a manic or mixed episode to remission. The results indicate a role for DNA and RNA damage by oxidation in BD pathophysiology and a potential for urinary 8-oxodG and 8-oxoGuo to function as biological markers of diagnosis, state and treatment response in BD.

Molecular cloning and characterisation of the mouse preprogalanin gene.

Using a probe obtained by PCR amplification from mouse genomic DNA, a genomic clone was isolated covering the entire mouse preprogalanin gene. The mouse gene has an exon:intron organisation very similar to that of the rat and human genes. The first exon is noncoding while exons 2-5 carry the coding region. Exon 6 also encodes the stop codon and a polyadenylation signal. The deduced amino-acid sequence of mouse preprogalanin is 94% and 68% identical to the rat and human peptide, respectively. The amino-acid sequence of mouse galanin was confirmed by RT-PCR amplification of mouse brain RNA. The cloning of the mouse galanin gene should allow elucidation of the regulatory characteristics of its promoter and facilitate transgenic approaches to the analysis of galanin gene function in this species.

Hyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors.

The neuropeptide galanin may have a role in modulation of nociception, particularly after peripheral nerve injury. The effect of galanin is mediated by at least three subtypes of receptors. In the present study, we assessed the nociceptive sensitivity in mice lacking the galanin receptor 1 gene (Galr1) and the development of neuropathic pain-like behaviours after photochemically induced partial sciatic nerve ischaemic injury. Under basal condition, Galr1 knock-out (Galr1(-/-)) mice had shortened response latency on the hot plate, but not tail flick and paw radiant heat, tests. The mechanical sensitivity was not different between Galr1(-/-) and wild type (Galr1(+/+)) mice, whereas the cold response was moderately enhanced in Galr1(-/-) mice. Both Galr1(-/-) mice and Galr1(+/+) controls developed mechanical and heat hypersensitivity after partial sciatic nerve injury. The duration of such pain-like behaviours was significantly increased in Galr1(-/-). The Galr1(-/-) mice and Galr1(+/+) mice did not differ in their recovery from deficits in toe-spread after sciatic nerve crush. The results provide some evidence for an inhibitory function for the neuropeptide galanin acting on galanin receptor 1 (GALR1) in nociception and neuropathic pain after peripheral nerve injury in mice.

A solid phase enzyme linked immunofiltration assay for secretory leucocyte proteinase inhibitor.

A solid phase enzyme linked immunosorbent filtration assay (ELIFA) has been developed for secretory leucocyte proteinase inhibitor (SLPI) utilising polyclonal anti-recombinant SLPI (anti-rSLPI) and polyclonal anti-bronchial mucus proteinase inhibitor (anti-BLPI) IgG samples. Millipore HATF nitrocellulose 96-well plates were used as receptacles for the assay and a commercial goat anti-rabbit IgG alkaline phosphatase conjugate was used as a secondary antibody for quantitation of levels of primary antibodies bound to rSLPI in the plate wells. Antigen bound to the HATF plates efficiently and the washing/blocking steps were simplified by vacuum filtration of samples resulting in a rapid and convenient assay system. The ELIFA was also sensitive and a detection limit of 0.1 ng SLPI/well was achieved using either anti-SLPI or anti-BLPI as primary antibodies. This assay was used to demonstrate the production of SLPI at moderate levels (0.5-3 ng/ml media) by human articular chondrocytes grown in monolayer culture.

Impact of epilepsy on employment status: findings from a UK study of people with well-controlled epilepsy.

This paper examines the current employment status and recent employment history of 494 individuals with epilepsy whose seizures were well-controlled or in remission. Information about employment status and history was obtained by means of self-completion questionnaires, sent to eligible subjects by post. The sampling frame from which subjects were recruited were neurology out-patient departments across the UK. The majority of subjects had epilepsy in remission: only 15% had had a seizure in the last year and only 25% reported one in the last two years. A high proportion of respondents were currently in employment. Of those who were not, few attributed this to their epilepsy; nor did epilepsy seem to have a significant impact on recent employment history. In spite of the lack of evidence of any actual discrimination, a third of respondents nevertheless felt their condition affected their ability to obtain employment. The findings from earlier studies of high unemployment rates partly reflect bias in the samples studied. Our data provide evidence that where seizures are well-controlled and uncomplicated by other handicap, people with epilepsy do not generally experience problems with employment.

The associations of psychopathology in epilepsy: a community study.

There is a plethora of studies documenting the association between psychosocial disadvantage and epilepsy but a paucity of studies explaining the precise nature of that relationship. Previous studies have been hampered by methodological problems including small sample size and selection bias. This study examined the aetiology of psychopathology in epilepsy in a cross-sectional community study. A significant proportion of patients were anxious and depressed and many reported side effects of their medication. Stepwise multiple regression techniques were employed to examine the relationship between clinical, demographic and psychosocial variables. Results indicated that psychosocial variables were the best predictors of each other but when these were taken into account, patient perceived seizure severity was an important predictor variable in understanding the relationship between epilepsy and psychosocial functioning.

The impact of counselling with a practical statistical model on patients' decision-making about treatment for epilepsy: findings from a pilot study.

To ascertain the impact of a computer-based predictive model on patients' decisions about continuing treatment of their epilepsy, 72 subjects were asked to complete questionnaires prior to and following counselling with the model. The subjects were attending the neurology out-patient clinic in a large UK hospital, and were identified from medical records as eligible for withdrawal of AEDs. The effect of counselling with the model was to make the majority of patients opt to continue AED therapy. Positive or negative framing of risk information appeared to influence the decisions of patients who were initially uncertain about continuing treatment, as did patients' perceptions of the clinician's views. The prognostic model appeared to allow relatively complex statistical information to be conveyed to patients in an accessible form. We suggest its use will aid clinicians in counselling patients and will help patients reach better-informed decisions about treatment.

Measuring the impact of epilepsy: the development of a novel scale.

The impact of a chronic illness is experienced not only through its physical symptoms, but also as a result of its effect on psychosocial functioning. In the case of an illness such as epilepsy, where the physical manifestations are transient, the psychosocial consequences may, with time, come to be of greater concern. We have been involved in developing a quality of life model for epilepsy. As part of the refinement of the initial model, we have devised a novel scale to measure the impact of the condition on a number of different aspects of daily life. The scale was administered to 75 patients attending an epilepsy out-patient clinic. Initial analysis of its psychometric properties is encouraging, although the inclusion of an item relating to employment reduced the scale's reliability. As a result, the wording of the existing item has been amended and an additional item has been incorporated. We hope the scale will be useful in investigations of treatment for epilepsy and of its psychosocial aspects.

The initial development of a health-related quality of life model as an outcome measure in epilepsy.

Patients with refractory epilepsy, despite no fixed physical deficit, are often socially and psychologically handicapped. Currently available outcome measures for epilepsy do not adequately address these manifestations or their influence on well-being and quality of life. A patient-based health-related quality of life (HRQL) model for epilepsy including physical, social and psychological domains was constructed. It contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, mastery, social satisfaction and general health and a specifically designed seizure severity scale with patient- and carer-based components. The psychometric properties of this model were evaluated in the context of the trial of a potential new antiepileptic drug. All the scales, except the Social Problems Questionnaire, have acceptable internal consistency (alpha 0.69-0.85) in this patient population. Construct validity is indicated by the ability of the scales to differentiate between groups of patients predicted to have different levels of psychosocial function. Treatment effects were detected by the patient (P = 0.017) and carers (P = 0.035) subscales of the seizure severity scale, the happiness (P = 0.003) and the mastery (P = 0.003) scales. Despite obvious deficiencies preliminary analyses are encouraging. This model provides a framework for investigating the complex interaction between the physical, social and psychological manifestations of epilepsy. The model has potential as an outcome measure for use in longitudinal studies and as a measure of disability for use in cross-sectional studies designed to compare quality of life in different populations of people with epilepsy.

Seizure frequency, patient-perceived seizure severity and the psychosocial consequences of intractable epilepsy.

It is generally recognised that the assessment of treatment effects in epilepsy using seizure frequency as the only outcome measure may lack sensitivity. A patient-based seizure severity scale has been developed and initial results confirm its reliability and validity. As part of the further development of this scale it is important to explore the relationship between seizure severity, seizure frequency and the psychosocial consequences of intractable epilepsy. One hundred patients with medically refractory partial seizures completed a quality of life questionnaire including measures of physical (seizure severity and frequency), social and psychological well-being (anxiety, depression, self-esteem, locus of control and happiness). Multivariate analysis demonstrated that individual psychological variables were best predicted by other psychological variables. However, when these were removed from analysis, seizure severity was the most significant predictor of self-esteem (P = 0.005), locus of control P = 0.039) and anxiety (P = 0.048). Seizure frequency did not contribute significantly to the variance of any of the psychological factors. These results highlight the importance of considering seizure severity when assessing treatment effects in epilepsy and provide further evidence for the construct validity of a novel patient-based seizure severity scale.

Assessing quality of life in patients with epilepsy.

The importance of quality-of-life (QOL) assessments in providing quantified information about the impact of chronic illness and its treatment is now generally accepted. For epilepsy, QOL assessment is a relatively recent development, but it is increasingly included within clinical trial protocols. Clinical trials in epilepsy that have included a comprehensive QOL assessment, although still relatively few in number, have examined the effectiveness both of broad management policies and of individual drug therapies. There are a number of important conceptual, methodological and practical issues behind the measurement of quality of life as an outcome of care in epilepsy that are being addressed through current efforts to develop standardised QOL instruments. In trying to assess quality of life in epilepsy, as in any other condition, it is important to satisfy the universal requirements of a scientific instrument-that it be valid, reliable, sensitive in change and practical. To date, the main 'formal' approaches to QOL assessment in epilepsy have involved the development of a novel QOL measure from first principles, customising of a previously developed generic measure, identification of a battery of generic and disease-specific scales addressing specific QOL domains, and adoption of an individual patient-generated approach. These various efforts have produced a battery of potentially valuable tools and approaches. Although QOL assessment is now mainly on the epilepsy research agenda, some important challenges remain to be met. These include the development of comprehensive, age-related measures for children with epilepsy, further investigation of the psychometric properties of the available measures for adults, issues of cross-cultural application and use with proxy informants, and the development of utility-based measures.

Epilepsy and the quality of everyday life. Findings from a study of people with well-controlled epilepsy.

Epilepsy is a stigmatising disorder and available evidence suggests that its diagnosis can have important psychosocial consequences and severely reduce the quality of an individual's everyday life. A number of studies have examined the psychosocial aspects of living with epilepsy, but these have generally involved groups of patients with severe or intractable epilepsy, so that the prevalence of problems may be over-estimated. The present study examined psychosocial functioning in a group of people in whom epilepsy was well-controlled; the majority had been seizure-free for at least two years. In doing so, it drew upon a model of quality of life which incorporated physical, social and psychological domains. Among this group of people, psychosocial functioning and adjustment to epilepsy appeared high, with low reported levels of distress. This is an important finding, not least for people with epilepsy themselves.

Felt versus enacted stigma: a concept revisited. Evidence from a study of people with epilepsy in remission.

Epilepsy is, in the majority of cases, a short-lived and self-limiting clinical condition. However, individuals labelled as epileptic frequently continue to feel stigmatised, even after their seizures remit. This paper describes the nature and extent of stigma in a group of individuals with epilepsy in remission. The distinction between 'felt' and 'enacted' stigma is examined, and found to be supported by the data.