Impulsive suicide attempts among young people-A prospective multicentre cohort study in Sweden.

BACKGROUND: We aimed to compare the prevalence of impulsive suicide attempts (ISA) among young adults and those over 25 who present at hospital in connection with attempted suicide. We also aimed to identify factors associated with ISA in young adults and to assess medical severity as well as the probability of repeated suicide attempts in this age group. METHOD: A prospective multicentre cohort study included hospital known cases of suicide attempt (N = 666). The prevalence of ISA was compared between young adults (18-25) and adults aged > 26. We used logistic regression models to identify factors associated with ISA, associations of ISA with high medical severity and prediction of new fatal or non-fatal suicide attempts within 6 months. RESULTS: 43.7% of the young patients had made an ISA, and 30.2% among those aged > 26 (p = 0.001). Among the young, substance use disorder was associated with ISA; crude odds ratio (OR) 2.0 (1.0-4.2), and adjusted OR 2.1 (0.99-4.4). Affective disorder and unemployment/ sickness absence implied lower odds of ISA. ISA resulted in injuries of high medical severity as often as more planned attempts and non-fatal or fatal repetition within 6 months was equally common (30%) in both groups. LIMITATIONS: The study was set in psychiatric emergency services, which limits the generalizability. CONCLUSIONS: Clinicians should acknowledge that suicide attempts among youth often occur without previous planning and may result in medically severe injuries. The probability of new fatal or non-fatal suicide attempts should be kept in mind also after an impulsive suicide attempt.

Mental illness and suicide after self-harm among young adults: long-term follow-up of self-harm patients, admitted to hospital care, in a national cohort.

BACKGROUND: Self-harm among young adults is a common and increasing phenomenon in many parts of the world. The long-term prognosis after self-harm at young age is inadequately known. We aimed to estimate the risk of mental illness and suicide in adult life after self-harm in young adulthood and to identify prognostic factors for adverse outcome. METHOD: We conducted a national population-based matched case-cohort study. Patients aged 18-24 years (n = 13 731) hospitalized after self-harm between 1990 and 2003 and unexposed individuals of the same age (n = 137 310 ) were followed until December 2009. Outcomes were suicide, psychiatric hospitalization and psychotropic medication in short-term (1-5 years) and long-term (>5 years) follow-up. RESULTS: Self-harm implied an increased relative risk of suicide during follow-up [hazard ratio (HR) 16.4, 95% confidence interval (CI) 12.9-20.9). At long-term follow-up, 20.3% had psychiatric hospitalizations and 51.1% psychotropic medications, most commonly antidepressants and anxiolytics. There was a six-fold risk of psychiatric hospitalization (HR 6.3, 95% CI 5.8-6.8) and almost three-fold risk of psychotropic medication (HR 2.8, 95% CI 2.7-3.0) in long-term follow-up. Mental disorder at baseline, especially a psychotic disorder, and a family history of suicide were associated with adverse outcome among self-harm patients. CONCLUSION: We found highly increased risks of future mental illness and suicide among young adults after self-harm. A history of a mental disorder was an important indicator of long-term adverse outcome. Clinicians should consider the substantially increased risk of suicide among self-harm patients with psychotic disorders.

Age-specific suicide mortality following non-fatal self-harm: national cohort study in Sweden.

BACKGROUND: Possible age-related differences in risk of completed suicide following non-fatal self-harm remain unexplored. We examined associations between self-harm and completed suicide across age groups of self-harming patients, and whether these associations varied by violent index method, presence of mental disorder, and repeated self-harm. METHOD: The design was a cohort study with linked national registers in Sweden. The study population comprised individuals aged ⩾10 years hospitalized during 1990-1999 due to non-fatal self-harm (n = 53 843; 58% females) who were followed for 9-19 years. We computed hazard ratios (HRs) across age groups (age at index self-harm episode), with time to completed suicide as outcome. RESULTS: The 1-year HR for suicide among younger males (10-19 years) was 14.6 [95% confidence interval (CI) 4.1-51.9] for violent method and 8.4 (95% CI 1.8-40.0) for mental disorder. By contrast, none of the three potential risk factors increased the 1-year risks in the youngest females. Among patients aged ⩾20 years, the 1-year HR for violent method was 4.6 (95% CI 3.8-5.4) for males and 10.4 (95% CI 8.3-13.0) for females. HRs for repeated self-harm during years 2-9 of follow-up were higher in 10- to 19-year-olds (males: HR 4.0, 95% CI 2.0-7.8; females: HR 3.7, 95% CI 2.1-6.5). The ⩾20 years age groups had higher HRs than the youngest, particularly for females and especially within 1 year. CONCLUSIONS: Violent method and mental disorder increase the 1-year suicide risk in young male self-harm patients. Further, violent method increases suicide risk within 1 year in all age and gender groups except the youngest females. Repeated self-harm may increase the long-term risk more in young patients. These aspects should be accounted for in clinical suicide risk assessment.

Low long-term efficacy and tolerability of add-on rufinamide in patients with Dravet syndrome.

In this retrospective European multicenter study we evaluated the efficacy and tolerability of rufinamide in patients with Dravet syndrome and refractory seizures. Twenty patients were included; in 16 patients a SCN1A mutation was detected. The responder rate after 6 months was 20%, and after 34 months, 5%. The retention rate was 45% after 6 months and 5% after 34 months. Rufinamide treatment was stopped because of aggravation of seizures (30%), no effect (45%), and side effects (10%). The efficacy and long-term retention rate were low in our patients with Dravet syndrome and refractory seizures, far lower than in patients with Lennox-Gastaut syndrome; one-third of our patients experienced seizure aggravation. Therefore, rufinamide does not seem to be a suitable option for long-term treatment in patients with Dravet syndrome.

Performance-based self-esteem and burnout in a cross-sectional study of medical students.

OBJECTIVES: To examine levels of burnout among medical students and test the hypothesis that high performance-based self-esteem is associated with burnout. Further to study associations between burnout and self-rated health. DESIGN: Cross-sectional survey, of medical students at 1st, 3rd and 6th year of medical school, N = 342, 59.1% women. MEASURES: Burnout was monitored by the Oldenburg Burnout Inventory (OLBI), comprising Exhaustion and Disengagement dimensions. Performance-based self-esteem (PBSE) was assessed by the PBSE-scale (PBSS) and self-rated health by SRH-5. RESULTS: The response rate was 90.4%. Females were more exhausted than males and sixth year students were most disengaged. High performance-based self-esteem was present in 41.7% of the respondents and poor health in 10.7%. Performance-based self-esteem had significant and moderate correlations with both burnout dimensions. Logistic regression showed a positive association between poor health and Exhaustion. CONCLUSIONS: Exhaustion among medical students was significantly associated with poor health, and deserves attention from teachers. Performance-based self-esteem was higher than in other populations and associated with both burnout dimensions, but not with poor health. Further research on study environment and burnout is needed, and the reasons for female students' higher exhaustion levels should be further investigated.

Levels of dopamine in blood and brain following nasal administration to rats.

The aim of this study was to investigate the levels of [(3)H]dopamine in blood, the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out whether the drug is transferred along the olfactory pathway to the central nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was given to male Sprague-Dawley rats either intravenously or nasally to the right nostril. For the absorption study, blood samples were withdrawn from the carotid artery. The CSF samples were taken by cisternal puncture and then brain tissue samples were excised. The presence of unchanged dopamine in the samples was ascertained using thin layer chromatography (TLC). The radioactivity in the samples was measured using liquid scintillation. The greatest amount of the total radioactivity absorbed from the nasal mucosa into the systemic circulation was observed at the first sampling point 15 min after administration. The bioavailability of the total radioactivity was 68+/-30%. The uptake of [(3)H]dopamine in the brain was significantly higher 30 min after nasal administration than after intravenous administration (P<0.01). TLC data showed that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb, CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion, these results show that unchanged dopamine is transferred into the olfactory bulb via the olfactory pathway in rats.

Nasal administration of a physostigmine analogue (NXX-066) for Alzheimer's disease to rats.

The nasal route has been receiving attention for the administration of systemically active drugs because delivery is convenient, reliable and rapid. The aims of this study were to investigate the systemic absorption of nasally administered (3aS)-cis-1, 2, 3, 3a, 8, 8a-hexahydro-1, 3a, 8-trimethyl-pyrrolo-[2,3b]-indol-5-yl 3, 4 dihydro-2-isoquinolincarboxylate (NXX-066), a physostigmine analogue, in rats and to compare the uptake of the drug into the cerebrospinal fluid (CSF) after nasal and intravenous administration. NXX-066 (3 micromol/kg) was administered to both nostrils or into the vena jugularis of male Sprague-Dawley rats. Blood and CSF samples were obtained at regular intervals from the arteria carotis and by cisternal puncture, respectively. The concentrations of NXX-066 in the blood and CSF samples were measured using HPLC with fluorescence detection. NXX-066 was absorbed rapidly after nasal administration with the peak concentration occurring within 1.5 min. The nasal bioavailability of NXX-066 was 100+/-30% and the elimination from plasma was as rapid as that following intravenous administration. Low concentrations of NXX-066 were detected in the CSF after both intravenous and nasal administration. In conclusion, NXX-066 was rapidly and totally absorbed into the systemic circulation and uptake into the CSF was not enhanced by nasal administration in rats.

Transfer of dopamine in the olfactory pathway following nasal administration in mice.

PURPOSE: The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. The precise localisation of dopamine radioactivity in the brain was studied using autoradiography. The presence of dopamine or its metabolites in the olfactory bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS: After administration of [3H]-dopamine into the right nostril, the amount of dopamine in the right bulb increased with time until. after 4 h, it was 27 times higher than in the left bulb. Among the other brain tissue samples, significantly higher amount of radioactivity was detected in the lateral olfactory tract. Radioactivity in the right olfactory bulb was shown by autoradiography to be selectively located in the peripheral layers 1 to 4 h after administration. Selective uptake of radioactivity was not seen in other regions of the brain. TLC data indicated that approximately 75% and 10% of the radioactivity in the olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The results indicate that unchanged dopamine is transferred into the olfactory bulb following nasal administration of [3H]-dopamine.

Reduction of epileptiform activity in response to low-dose clonazepam in children with epilepsy: a randomized double-blind study.

PURPOSE: To evaluate the effect of low-dose clonazepam (CZP) on the amount of epileptiform activity in children with focal and generalized epilepsy. METHODS: In a single-blind pilot study, followed by a double-blind, placebo-controlled, randomized, crossover study, 15 children with epilepsy were evaluated by using 24-h long-term EEG recordings during baseline days and days after injections of placebo and CZP. The drug was given as a single i.m. injection of 0.02 mg/kg BW. Blood samples were obtained regularly for analysis of plasma concentrations of CZP. The number of epileptiform discharges was determined during corresponding periods with the individual child in the same state of alertness, the same real time of day, and with concomitant antiepileptic drugs (AEDs) unchanged. RESULTS: In the double-blind study, low-dose CZP produced a highly significant (p = 0.0015) decrease in the amount of epileptiform activity (mean, -69% vs. placebo, -2%) obtained during periods when median plasma concentrations ranged from 18 to <14 nM. The maximal plasma level (median, 24 nM) was reached before the start of the analysis periods. The pilot study showed reductions of epileptiform discharges within the same range as the double-blind study. In the children with daily seizures, a parallel decrease in seizures and the number of epileptiform discharges was seen after the administration of CZP. CONCLUSIONS: Our data demonstrate a significant reduction of epileptiform discharges on long-term EEGs after a single low dose of CZP with concomitant low plasma levels, which were considerably lower than the doses and plasma levels usually recommended. A concomitant reduction of seizures also was seen.

Nasal absorption of (S)-UH-301 and its transport into the cerebrospinal fluid of rats.

Targeting the brain via nasal administration of drugs has been studied frequently over the last few years. In this study, the serotonin-1a receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropyl-amino) tetralin ((S)-UH-301) hydrochloride was used as a model substance. The systemic absorption and transport of (S)-UH-301 into male Sprague-Dawley rat cerebrospinal fluid (CSF) were investigated after nasal and intravenous administration. Blood and CSF samples were obtained at regular time intervals from the arteria carotis and by cisternal puncture, respectively, after administration to both nostrils (total 12 micromol/kg) or into the vena jugularis (6 micromol/kg). The concentrations of (S)-UH-301 in plasma and CSF were measured by HPLC with electrochemical detection. The maximum plasma concentration of intranasal (S)-UH-301 occurred in about 7 min and the absolute bioavailability seemed to be complete (F=1.2+/-0.4). Initially, no increased concentrations of (S)-UH-301 were seen in CSF after nasal compared to intravenous administration i.e. it appeared that no direct transport of (S)-UH-301 from the nasal cavity, along the olfactory neurons and into the CSF occurred. However, a prolonged duration of the concentration was seen after nasal administration of (S)-UH-301 and after about 20 min the CSF(na):CSF(iv) concentration ratio (corrected for different dosage) exceeded 1.

Inferring children's categorizations from sequential touching behaviors: an analytical model.

A child is assumed to belong to 1 of 2 classes: categorizer or noncategorizer. To determine which, 4 toy animals and 4 toy vehicles were randomly arrayed for touching for 2 min. The task was to infer whether the child was a categorizer or a noncategorizer for vehicles and similarly for animals. A model is proposed that assumes a child's sequence of touches follows one probability distribution if the child is a categorizer and another distribution if the child is a noncategorizer. The proportion of children in each category and the probability of a child being a categorizer for, say, vehicles are among the quantities that can be estimated. Data from 18-month-old children are illustrative. The model appears efficient and robust.

Variability of epileptiform activity in long-term EEGs with short and long intervals in children with epilepsy.

OBJECTIVE: To evaluate the impact of the time factor on the amount of epileptiform activity in long-term EEG recordings in children with epilepsy. METHODS: Ten children with epilepsy of different types underwent three 24 h EEG examinations during two consecutive days and with a month's interval. The number of epileptiform discharges during selected corresponding periods of time was counted. RESULTS: The number of epileptiform discharges on three repeated examination days showed no significant difference (ANOVA P = 0.88) as intraindividual increases and decreases on different days counterbalanced each other within the group. However the standard deviations of the relative changes were larger between recordings with a month's interval compared to those for consecutive days (86% and 33%). The mean magnitude of change was 55% between days separated by a month compared to 24% on consecutive days. The difference was non-significant but showed a trend towards larger changes with a longer interval (P = 0.07). CONCLUSIONS: The variability of epileptiform activity was larger when the interval between recordings was 1 month compared to consecutive days. The magnitude of the relative changes between intervals of 1 and 30 days showed a trend towards a difference although not statistically significant. When evaluating repeated long-term EEGs in relation to therapy in children, these variations should be considered.

Treatment of spasticity in children with low dose benzodiazepine.

In an attempt to investigate whether benzodiazepines at low dosage have a significant effect in reducing spasticity among children with cerebral palsy, we carried out a double-blind, placebo-controlled, cross-over study. Twelve children with either spastic diplegia or hemiplegia participated in this study. The mean age was 14 years. The restraint of passive knee movements was determined with a dynamic dynamometer and spastic stretch reflexes were measured as EMG activity in muscles stretched. Clonazepam was given at low dosage (0.02 mg/kg body weight). In each child measurements of passive restraint were made on 2 different days immediately before and 3 h after an i.m. injection of either clonazepam or placebo in randomized order. Clonazepam significantly reduced spastic restraint (P < 0.001) compared to non-significant reduction with placebo. The mean plasma concentration of clonazepam at time of spasticity evaluation was 21 mmol/l which is in the low dose range, far below conventional doses. The study thus shows a positive effect of low dose clonazepam in reducing spasticity in children when given as a single dose.