Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Habitat-dependent changes in vigilance behaviour of Red-crowned Crane influenced by wildlife tourism

The Endangered Red-crowned Crane (Grus japonensis) is one of the most culturally iconic and sought-after species by wildlife tourists. Here we investigate how the presence of tourists influence the vigilance behaviour of cranes foraging in Suaeda salsa salt marshes and S. salsa/Phragmites australis mosaic habitat in the Yellow River Delta, China. We found that both the frequency and duration of crane vigilance significantly increased in the presence of wildlife tourists. Increased frequency in crane vigilance only occurred in the much taller S. salsa/P. australis mosaic vegetation whereas the duration of vigilance showed no significant difference between the two habitats. Crane vigilance declined with increasing distance from wildlife tourists in the two habitats, with a minimum distance of disturbance triggering a high degree of vigilance by cranes identified at 300 m. The presence of wildlife tourists may represent a form of disturbance to foraging cranes but is habitat dependent. Taller P. australis vegetation serves primarily as a visual obstruction for cranes, causing them to increase the frequency of vigilance behaviour. Our findings have important implications for the conservation of the migratory red-crowned crane population that winters in the Yellow River Delta and can help inform visitor management

Les galets peints de la grotte de Chaves.

We present her some thirty painted blocks found in the Neolithic level of Chaves cave that show geometric and figurative decoration. Complex themes (anthropomorphic figures, crosses, groups of convergent lines) were concentrated oover a paved surface, which presented a geat quantity oof ashes. There were oother blocks ( the ones with vertical lines) that were associated with two pits opened in the cardial pottery level. The existencee of a praying figure in a block remembers the cadial world of Coova de l\u27Or and the parietal art of Petracos. Other themes (anthropmophic cosses in \u3c\u3c phi\u3e\u3e, triangular-headed figre) are similar to those oof schematic art, for which a Nelithic chronology is propoosed in Aagon

Les galets peints de la grotte de Chaves.

We present her some thirty painted blocks found in the Neolithic level of Chaves cave that show geometric and figurative decoration. Complex themes (anthropomorphic figures, crosses, groups of convergent lines) were concentrated oover a paved surface, which presented a geat quantity oof ashes. There were oother blocks ( the ones with vertical lines) that were associated with two pits opened in the cardial pottery level. The existencee of a praying figure in a block remembers the cadial world of Coova de l\u27Or and the parietal art of Petracos. Other themes (anthropmophic cosses in \u3c\u3c phi\u3e\u3e, triangular-headed figre) are similar to those oof schematic art, for which a Nelithic chronology is propoosed in Aagon

Pautas de movilidad en el Pirineo central durante el Neolítico antiguo: una aproximación a partir de los recursos líticos

Con el presente estudio preliminar hemos presentado un cuadro general sobre los tipos de rocas explotadas en tres yacimientos del Neolítico antiguo del Pirineo Aragonés

The Beginning of High Mountain Occupations in the Pyrenees. Human Settlements and Mobility from 18,000 cal BC to 2000 cal BC

During the last two decades, the archaeological research carried out in the Pyrenees challenged the traditional images of the past in this mountain area. The archaeological sequence of the range goes back and sites like Balma Margineda, treated until recently as an exception, now are seen as part of more global process. Actual data suggest that main valleys of the Pyrenean frequented by humans at the end of the last glacial period, with sites slightly over 1000 o.s.l. After the Younger Dryas, the human presence ascended to alpine and subalpine areas, in accordance with current archaeological data. The Neolisitation process was early in some hillsides, with intense remains of farming and pastoralism in many sites from dated in the second half of the 6th millennia cal BC. Human settlements like Coro Tracito, Els Trocs and El Sardo confirm the full introduction of agrarian activity in the central part of the Pyrenees between 5300 and 4600 cal BC. After 3500/3300 cal BC the indices oh sheepherding rises to alpine areas, with an abrupt increase of known archaeological sites in alpine areas, above the current timberline. This phenomena, as well as the signs of anthropic disturbance of the alpine environment in sedimentary sequences, suggests a more stable and ubiquitous human presence, probably largely associated with the development of mobile herding practices.This paper has been carried out in the frame of the GAAM/AGREST research activity. More specifically, this study is part of the projects “Análisi ecológico de la culturización del paisaje de alta montaña desde el Neolítico: los Parques Nacionales de montaña como modelo (CUL-PA)” funded by the Ministry of Agriculture, Food and Environment (Spain) and directed by J. Catalán and “Modelización de los espacios prehistóricos de montaña. Un SIG del patrimonio arqueológico y los territorios pastoriles” (HAR2015-66780-P, MINECO/FEDER) funded by the Ministry of Economy and Competitiveness (Spain) and directed by E. Gassiot.Peer reviewe