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.

Assédio moral em estudantes trabalhadores e sua relação com o bem-estar no trabalho / Mobbing in student workers and their relationship to well-being at work

Este trabalho tem o intuito de investigar o assédio moral e as possíveis relações com o bem-estar notrabalho. Foram aplicados o Questionário Biosociodemográfico e Laboral, o Questionário de AtosNegativos - QAN e as Medidas de Bem-estar no Trabalho em 457 acadêmicos de graduação. Osresultados mostraram que há relação entre o assédio moral e as medidas de bem-estar no trabalho(p<0,05), indicando que a presença da violência psicológica causa uma diminuição no bem-estar laboral.Na análise de regressão linear, alguns atos negativos no trabalho foram preditores de duas dimensões dasmedidas de bem estar no trabalho. Estes resultados sugerem que a ocorrência de assédio moral estáassociada a menor satisfação e comprometimento no trabalho(AU)

Assédio moral em estudantes trabalhadores e sua relação com o bem-estar no trabalho / Mobbing in student workers and their relationship to well-being at work

Este trabalho tem o intuito de investigar o assédio moral e as possíveis relações com o bem-estar . Foram aplicados o Questionário Biosocio demográfico e Laboral, o Questionário de Atos Negativos - QAN e as Medidas de Bem-estar no Trabalho em 457 acadêmicos de graduação. Os resultados mostraram que há relação entre o assédio moral e as medidas de bem-estar no trabalho(p<0,05), indicando que a presença da violência psicológica causa uma diminuição no bem-estar laboral.Na análise de regressão linear, alguns atos negativos no trabalho foram preditores de duas dimensões das medidas de bem estar no trabalho. Estes resultados sugerem que a ocorrência de assédio moral está associada a menor satisfação e comprometimento no trabalho

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.

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.

Exploring areas of consensus and conflict around values underpinning public involvement in health and social care research: a modified Delphi study.

OBJECTIVE: There is growing interest in the potential benefits of public involvement (PI) in health and social care research. However, there has been little examination of values underpinning PI or how these values might differ for different groups with an interest in PI in the research process. We aimed to explore areas of consensus and conflict around normative, substantive and process-related values underpinning PI. DESIGN: Mixed method, three-phase, modified Delphi study, conducted as part of a larger multiphase project. SETTING: The UK health and social care research community. PARTICIPANTS: Stakeholders in PI in research, defined as: clinical and non-clinical academics, members of the public, research managers, commissioners and funders; identified via research networks, online searches and a literature review. RESULTS: We identified high levels of consensus for many normative, substantive and process-related issues. However, there were also areas of conflict in relation to issues of bias and representativeness, and around whether the purpose of PI in health and social care research is to bring about service change or generate new knowledge. There were large differences by group in the percentages endorsing the ethical justification for PI and the argument that PI equalises power imbalances. With regard to practical implementation of PI, research support infrastructures were reported as lacking. Participants reported shortcomings in the uptake and practice of PI. Embedding PI practice and evaluation in research study designs was seen as fundamental to strengthening the evidence base. CONCLUSIONS: Our findings highlight the extent to which PI is already embedded in research. However, they also highlight a need for 'best practice' standards to assist research teams to understand, implement and evaluate PI. These findings have been used in developing a Public Involvement Impact Assessment Framework (PiiAF), which offers guidance to researchers and members of the public involved in the PI process.

Predictors of positive and negative attitudes toward their condition in Turkish individuals with epilepsy.

The purpose of this cross-sectional study was to explore the attitudes of individuals with epilepsy (IWE) toward their condition via self-reported changes in the feelings/thoughts about having epilepsy. We aimed to investigate whether individuals with epilepsy perceive a change in their initial attitudes toward the condition over time. Additionally, if a change was perceived, the variables which predict the current thoughts/feelings toward epilepsy were also examined. Seventy adult IWE participated in the study. Of the 70 participants in the study, 25.7% retained their initial feelings/thoughts without any change. Among the IWE who reported no-change, the most common category was "negative from the beginning". On the other hand, 74.3% of the participants reported a change. Of the 74.3% of participants reporting change, the most common direction was from negative to positive" (79.2%) seeming to indicate a positive adjustment over the passage of time. In a logistic regression, only three factors were found to predict positive feelings/thoughts toward epilepsy: a clear understanding of the condition, low levels of depression and current employment status. Finally, there is a discussion of the potential applications of the IWE' self-assessment of their attitudes.

Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists.

OBJECTIVES: To provide information on the frequency and reasons for outcome reporting bias in clinical trials. DESIGN: Trial protocols were compared with subsequent publication(s) to identify any discrepancies in the outcomes reported, and telephone interviews were conducted with the respective trialists to investigate more extensively the reporting of the research and the issue of unreported outcomes. PARTICIPANTS: Chief investigators, or lead or coauthors of trials, were identified from two sources: trials published since 2002 covered in Cochrane systematic reviews where at least one trial analysed was suspected of being at risk of outcome reporting bias (issue 4, 2006; issue 1, 2007, and issue 2, 2007 of the Cochrane library); and a random sample of trial reports indexed on PubMed between August 2007 and July 2008. SETTING: Australia, Canada, Germany, the Netherlands, New Zealand, the United Kingdom, and the United States. MAIN OUTCOME MEASURES: Frequency of incomplete outcome reporting-signified by outcomes that were specified in a trial's protocol but not fully reported in subsequent publications-and trialists' reasons for incomplete reporting of outcomes. RESULTS: 268 trials were identified for inclusion (183 from the cohort of Cochrane systematic reviews and 85 from PubMed). Initially, 161 respective investigators responded to our requests for interview, 130 (81%) of whom agreed to be interviewed. However, failure to achieve subsequent contact, obtain a copy of the study protocol, or both meant that final interviews were conducted with 59 (37%) of the 161 trialists. Sixteen trial investigators failed to report analysed outcomes at the time of the primary publication, 17 trialists collected outcome data that were subsequently not analysed, and five trialists did not measure a prespecified outcome over the course of the trial. In almost all trials in which prespecified outcomes had been analysed but not reported (15/16, 94%), this under-reporting resulted in bias. In nearly a quarter of trials in which prespecified outcomes had been measured but not analysed (4/17, 24%), the "direction" of the main findings influenced the investigators' decision not to analyse the remaining data collected. In 14 (67%) of the 21 randomly selected PubMed trials, there was at least one unreported efficacy or harm outcome. More than a quarter (6/21, 29%) of these trials were found to have displayed outcome reporting bias. CONCLUSION: The prevalence of incomplete outcome reporting is high. Trialists seemed generally unaware of the implications for the evidence base of not reporting all outcomes and protocol changes. A general lack of consensus regarding the choice of outcomes in particular clinical settings was evident and affects trial design, conduct, analysis, and reporting.

Adverse antiepileptic drug effects in new-onset seizures: a case-control study.

OBJECTIVE: Adverse effects (AEs) are a major concern when starting antiepileptic drug (AED) treatment. This study quantified the extent to which AE reporting in people with new-onset seizures started on AEDs is attributable to the medication per se, and investigated variables contributing to AE reporting. METHODS: We pooled data from 2 large prospective studies, the Multicenter Study of Early Epilepsy and Single Seizures and the Northern Manhattan Study of incident unprovoked seizures, and compared adverse event profile (AEP) total and factor scores between adult cases prescribed AEDs for new-onset seizures and untreated controls, adjusting for several demographic and clinical variables. Differences in AEP scores were also tested across different AED monotherapies and controls, and between cases and controls grouped by number of seizures. RESULTS: A total of 212 cases and 206 controls were identified. Most cases (94.2%) were taking low AED doses. AEP scores did not differ significantly between the 2 groups. Depression, female gender, symptomatic etiology, younger seizure onset age, ≥2 seizures, and history of febrile seizures were associated with higher AEP scores. There were no significant differences in AEP scores across different monotherapies and controls. AEP scores increased in both cases and controls with increasing number of seizures, the increment being more pronounced in cases. CONCLUSIONS: When AED treatment is started at low doses following new-onset seizures, AE reporting does not differ from untreated individuals. Targeting specific factors affecting AE reporting could lead to improved tolerability of epilepsy treatment.

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.

Socioeconomic differences in service use, payment and receipt of illness-related benefits in the last year of life: findings from the British Household Panel Survey.

BACKGROUND: Terminal illness presents a financial challenge to many households, but in Britain the situation should be eased by state benefits, such as attendance allowance, which is available to everyone in the last six months of life without means testing. AIM: To investigate the use of health and social services, payments and benefit receipt by individuals in differing financial circumstances in the year before death. METHODS: Analysis of individual level panel data for 1652 community-dwelling decedents from 12 waves of the British Household Panel Study (1991-2003). RESULTS: In the year before death, over 90% of decedents saw their GP, and around one-third spent some time in hospital. More than 80% paid no fees for any services. Over a third of decedents aged over 65 reported financial strain, but only 13.9% of these were receiving attendance allowance. People who felt that they were having financial difficulties were more likely to be frequent attenders in primary care, taking age, health status and other factors into account (adjusted OR=1.9, 95% CI=1.3-2.6, P<0.001). Older age was associated with less use of primary, but not secondary care. CONCLUSIONS: Financial strain was common, but benefit uptake low. Primary health care professionals saw nearly all decedents in their last year, and could play an important role in ensuring that the elderly and the less well off are aware of the services and benefits available to them.

Meanings of epilepsy in its sociocultural context and implications for stigma: findings from ethnographic studies in local communities in China and Vietnam.

We investigated beliefs about the causes, course, and treatment of epilepsy and its impact on quality of life (QOL) in key target groups, using "mini-ethnographies" involving 141 in-depth interviews and 12 focus groups in China, and 84 in-depth interviews and 16 focus groups in Vietnam. Data were analyzed thematically, using a qualitative data analysis package. In both countries, beliefs about causes and triggers of epilepsy and seizures were a complex interweaving of Western, traditional, and folk medicine concepts. Epilepsy was understood to be chronic, not curable, but controllable, and was seen as enormously socially disruptive, with wide-ranging impact on QOL. Our findings suggest a more "embodied" and benign set of theories about epilepsy than in some other cultural contexts; nonetheless, people with epilepsy are still seen as having low social value and face social rejection. By exploring meanings attached to epilepsy in these two cultural contexts, we have clarified reasons behind previously documented negative attitudes and foci for future intervention studies.

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.

Knowledge of and attitudes expressed toward epilepsy by carers of people with epilepsy: a UK perspective.

OBJECTIVE: The aim of this study was to investigate the knowledge and attitudes possessed by carers of people with epilepsy. METHODS: A postal survey of 2000 carers recruited from the membership list of a UK epilepsy charity was conducted using a standard set of questions. The questions covered their knowledge of epilepsy (e.g., estimating prevalence and identifying causes of epilepsy) and their attitudes (e.g., about the characteristics of people with epilepsy). RESULTS: Overall, 651 carers responded. Only 29% of carers were male, with the majority between 40 and 60 years of age. The majority of respondents (76%) overestimated the prevalence of epilepsy. Twenty-five percent believed that epilepsy was caused by stress. The majority of respondents believed that people with epilepsy were treated differently by others. Only a small percentage believed that people with epilepsy should be barred from such professions as teaching and nursing. CONCLUSIONS: Carers of people with epilepsy generally possessed high levels of knowledge about most aspects of epilepsy, and their attitudes toward those with epilepsy were benign. There were, however, particular groups who were more likely to hold more positive attitudes, and these included younger and better-educated individuals. Limitations of this study include that the sample was self-selected and that only a third of the people to whom the questionnaire was mailed responded.

Quality of life outcomes of immediate or delayed treatment of early epilepsy and single seizures.

OBJECTIVE: To compare the impact of policies of immediate vs deferred treatment in patients with few or infrequent seizures on quality of life (QoL) outcomes. METHODS: We conducted a multicenter, randomized, unblinded study of immediate and deferred treatment. QoL data were collected by mail, using validated measures, for participants living in the UK and without major learning disability. Baseline questionnaires were returned by 441 adult patients; 333 returned 2-year follow-up questionnaires. This analysis is based on 331 patients (162 randomized to immediate, 169 to deferred treatment) returning both baseline and 2-year questionnaires. RESULTS: There were no significant differences at 2 years in QoL outcomes by treatment group. Patients randomized to deferred treatment were no more likely to report impairments in general health, cognitive function, psychological well-being, or social function. The one area of functioning affected was driving, where those randomized to deferred treatment were disadvantaged. There were clear QoL impacts both of taking antiepileptic drugs and, to an even greater extent, of continuing seizures. CONCLUSIONS: In treatment uncertain patients, there is a clear trade-off between adverse effects of seizures and adverse effects of taking antiepileptic drugs, i.e., neither policy examined in our study was associated with overall quality of life gains or losses longer term.

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.

Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis.

BACKGROUND AND AIMS: Study of health related quality of life (HRQOL) and the factors responsible for its impairment in primary biliary cirrhosis (PBC) has, to date, been limited. There is increasing need for a HRQOL questionnaire which is specific to PBC. The aim of this study was to develop, validate, and evaluate a patient based PBC specific HRQOL measure. SUBJECTS AND METHODS: A pool of potential questions was derived from thematic analysis of indepth interviews carried out with 30 PBC patients selected to represent demographically the PBC patient population as a whole. This pool was systematically reduced, pretested, and cross validated with other HRQOL measures in national surveys involving a total of 900 PBC patients, to produce a quality of life profile measure, the PBC-40, consisting of 40 questions distributed across six domains. The PBC-40 was then evaluated in a blinded comparison with other HRQOL measures in a further cohort of 40 PBC patients. RESULTS: The six domains of PBC-40 relate to fatigue, emotional, social, and cognitive function, general symptoms, and itch. The highest mean domain score was seen for fatigue and the lowest for itch. The measure has been fully validated for use in PBC and shown to be scientifically sound. PBC patient satisfaction, measured in terms of the extent to which a questionnaire addresses the problems that they experience, was significantly higher for the PBC-40 than for other HRQOL measures. CONCLUSION: The PBC-40 is a short easy to complete measure which is acceptable to PBC patients and has significantly greater relevance to their problems than other frequently used HRQOL measures. Its scientific soundness, shown in extensive testing, makes it a valuable instrument for future use in clinical and research settings.

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.