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1. Optimal Management of Status Epilepticus in Children in the Emergency Setting: A Review of Recent Advances

Author

Messahel S, Bracken L, and Appleton R

Subjects
convulsive, status epilepticus, emergency, anti-seizure medications, anticonvulsants, paediatric, children, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Shrouk Messahel,1 Louise Bracken,2 Richard Appleton3 1NIHR NWC Speciality Research Lead for Trauma and Emergency Care, The Emergency Department, Alder Hey Children’s NHS Foundation Trust, Liverpool, L12 2AP, UK; 2Paediatric Medicines Research Unit, Alder Hey Children’s NHS Foundation Trust, Liverpool, L12 2AP, UK; 3Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 3BX, UKCorrespondence: Richard Appleton, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 3BX, UK, Tel +44 07976 010754, Email richardappleton55@hotmail.co.ukAbstract: Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.Keywords: convulsive, status epilepticus, emergency, anti-seizure medications, anticonvulsants, pediatric, children

Published
2022

2. Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Author

Gerritsen, S. E., van Bodegom, L. S., Dieleman, G. C., Overbeek, M. M., Verhulst, F. C., Wolke, D., Rizopoulos, D., Appleton, R., van Amelsvoort, T. A. M. J., Bodier Rethore, C., Bonnet-Brilhault, F., Charvin, I., Da Fonseca, D., Davidović, N., Dodig-Ćurković, K., Ferrari, A., Fiori, F., Franić, T., Gatherer, C., de Girolamo, G., Heaney, N., Hendrickx, G., Jardri, R., Kolozsvari, A., Lida-Pulik, H., Lievesley, K., Madan, J., Mastroianni, M., Maurice, V., McNicholas, F., Nacinovich, R., Parenti, A., Paul, M., Purper-Ouakil, D., Rivolta, L., de Roeck, V., Russet, F., Saam, M. C., Sagar-Ouriaghli, I., Santosh, P. J., Sartor, A., Schulze, U. M. E., Scocco, P., Signorini, G., Singh, S. P., Singh, J., Speranza, M., Stagi, P., Stagni, P., Street, C., Tah, P., Tanase, E., Tremmery, S., Tuffrey, A., Tuomainen, H., Walker, L., Wilson, A., and Maras, A.

Published
2022
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3. Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Author

Gerritsen, S, van Bodegom, L, Dieleman, G, Overbeek, M, Verhulst, F, Wolke, D, Rizopoulos, D, Appleton, R, van Amelsvoort, T, Bodier Rethore, C, Bonnet-Brilhault, F, Charvin, I, Da Fonseca, D, Davidovic, N, Dodig-Curkovic, K, Ferrari, A, Fiori, F, Franic, T, Gatherer, C, de Girolamo, G, Heaney, N, Hendrickx, G, Jardri, R, Kolozsvari, A, Lida-Pulik, H, Lievesley, K, Madan, J, Mastroianni, M, Maurice, V, Mcnicholas, F, Nacinovich, R, Parenti, A, Paul, M, Purper-Ouakil, D, Rivolta, L, de Roeck, V, Russet, F, Saam, M, Sagar-Ouriaghli, I, Santosh, P, Sartor, A, Schulze, U, Scocco, P, Signorini, G, Singh, S, Singh, J, Speranza, M, Stagi, P, Stagni, P, Street, C, Tah, P, Tanase, E, Tremmery, S, Tuffrey, A, Tuomainen, H, Walker, L, Wilson, A, Maras, A, Adams, L, Allibrio, G, Armando, M, Aslan, S, Baccanelli, N, Balaudo, M, Bergamo, F, Bertani, A, Berriman, J, Boon, A, Braamse, K, Breuninger, U, Buttiglione, M, Buttle, S, Schandrin, A, Cammarano, M, Canaway, A, Cantini, F, Cappellari, C, Carenini, M, Carra, G, Ferrari, C, Chianura, K, Coleman, P, Colonna, A, Conese, P, Costanzo, R, Daffern, C, Danckaerts, M, de Giacomo, A, Ermans, J, Farmer, A, Fegert, J, Ferrari, S, Galea, G, Gatta, M, Gheza, E, Goglia, G, Grandetto, M, Griffin, J, Levi, F, Humbertclaude, V, Ingravallo, N, Invernizzi, R, Kelly, C, Killilea, M, Kirwan, J, Klockaerts, C, Kovac, V, Liew, A, Lippens, C, Macchi, F, Manenti, L, Margari, F, Margari, L, Martinelli, P, Mcfadden, L, Menghini, D, Miller, S, Monzani, E, Morini, G, Mutafov, T, O'Hara, L, Negrinotti, C, Nelis, E, Neri, F, Nikolova, P, Nossa, M, Cataldo, M, Noterdaeme, M, Operto, F, Panaro, V, Pastore, A, Pemmaraju, V, Pepermans, A, Petruzzelli, M, Presicci, A, Prigent, C, Rinaldi, F, Riva, E, Roekens, A, Rogers, B, Ronzini, P, Sakar, V, Salvetti, S, Martinelli, O, Sandhu, T, Schepker, R, Siviero, M, Slowik, M, Smyth, C, Conti, P, Spadone, M, Starace, F, Stoppa, P, Tansini, L, Toselli, C, Trabucchi, G, Tubito, M, van Dam, A, van Gutschoven, H, van West, D, Vanni, F, Vannicola, C, Varuzza, C, Varvara, P, Ventura, P, Vicari, S, Vicini, S, von Bentzel, C, Wells, P, Williams, B, Zabarella, M, Zamboni, A, Zanetti, E, Gerritsen S. E., van Bodegom L. S., Dieleman G. C., Overbeek M. M., Verhulst F. C., Wolke D., Rizopoulos D., Appleton R., van Amelsvoort T. A. M. J., Bodier Rethore C., Bonnet-Brilhault F., Charvin I., Da Fonseca D., Davidovic N., Dodig-Curkovic K., Ferrari A., Fiori F., Franic T., Gatherer C., de Girolamo G., Heaney N., Hendrickx G., Jardri R., Kolozsvari A., Lida-Pulik H., Lievesley K., Madan J., Mastroianni M., Maurice V., McNicholas F., Nacinovich R., Parenti A., Paul M., Purper-Ouakil D., Rivolta L., de Roeck V., Russet F., Saam M. C., Sagar-Ouriaghli I., Santosh P. J., Sartor A., Schulze U. M. E., Scocco P., Signorini G., Singh S. P., Singh J., Speranza M., Stagi P., Stagni P., Street C., Tah P., Tanase E., Tremmery S., Tuffrey A., Tuomainen H., Walker L., Wilson A., Maras A., Adams L., Allibrio G., Armando M., Aslan S., Baccanelli N., Balaudo M., Bergamo F., Bertani A., Berriman J., Boon A., Braamse K., Breuninger U., Buttiglione M., Buttle S., Schandrin A., Cammarano M., Canaway A., Cantini F., Cappellari C., Carenini M., Carra G., Ferrari C., Chianura K., Coleman P., Colonna A., Conese P., Costanzo R., Daffern C., Danckaerts M., de Giacomo A., Ermans J. -P., Farmer A., Fegert J. M., Ferrari S., Galea G., Gatta M., Gheza E., Goglia G., Grandetto M. R., Griffin J., Levi F. M., Humbertclaude V., Ingravallo N., Invernizzi R., Kelly C., Killilea M., Kirwan J., Klockaerts C., Kovac V., Liew A., Lippens C., Macchi F., Manenti L., Margari F., Margari L., Martinelli P., McFadden L., Menghini D., Miller S., Monzani E., Morini G., Mutafov T., O'Hara L., Negrinotti C., Nelis E., Neri F., Nikolova P., Nossa M., Cataldo M. G., Noterdaeme M., Operto F., Panaro V., Pastore A., Pemmaraju V., Pepermans A., Petruzzelli M. G., Presicci A., Prigent C., Rinaldi F., Riva E., Roekens A., Rogers B., Ronzini P., Sakar V., Salvetti S., Martinelli O., Sandhu T., Schepker R., Siviero M., Slowik M., Smyth C., Conti P., Spadone M. A., Starace F., Stoppa P., Tansini L., Toselli C., Trabucchi G., Tubito M., van Dam A., van Gutschoven H., van West D., Vanni F., Vannicola C., Varuzza C., Varvara P., Ventura P., Vicari S., Vicini S., von Bentzel C., Wells P., Williams B., Zabarella M., Zamboni A., Zanetti E., Gerritsen, S, van Bodegom, L, Dieleman, G, Overbeek, M, Verhulst, F, Wolke, D, Rizopoulos, D, Appleton, R, van Amelsvoort, T, Bodier Rethore, C, Bonnet-Brilhault, F, Charvin, I, Da Fonseca, D, Davidovic, N, Dodig-Curkovic, K, Ferrari, A, Fiori, F, Franic, T, Gatherer, C, de Girolamo, G, Heaney, N, Hendrickx, G, Jardri, R, Kolozsvari, A, Lida-Pulik, H, Lievesley, K, Madan, J, Mastroianni, M, Maurice, V, Mcnicholas, F, Nacinovich, R, Parenti, A, Paul, M, Purper-Ouakil, D, Rivolta, L, de Roeck, V, Russet, F, Saam, M, Sagar-Ouriaghli, I, Santosh, P, Sartor, A, Schulze, U, Scocco, P, Signorini, G, Singh, S, Singh, J, Speranza, M, Stagi, P, Stagni, P, Street, C, Tah, P, Tanase, E, Tremmery, S, Tuffrey, A, Tuomainen, H, Walker, L, Wilson, A, Maras, A, Adams, L, Allibrio, G, Armando, M, Aslan, S, Baccanelli, N, Balaudo, M, Bergamo, F, Bertani, A, Berriman, J, Boon, A, Braamse, K, Breuninger, U, Buttiglione, M, Buttle, S, Schandrin, A, Cammarano, M, Canaway, A, Cantini, F, Cappellari, C, Carenini, M, Carra, G, Ferrari, C, Chianura, K, Coleman, P, Colonna, A, Conese, P, Costanzo, R, Daffern, C, Danckaerts, M, de Giacomo, A, Ermans, J, Farmer, A, Fegert, J, Ferrari, S, Galea, G, Gatta, M, Gheza, E, Goglia, G, Grandetto, M, Griffin, J, Levi, F, Humbertclaude, V, Ingravallo, N, Invernizzi, R, Kelly, C, Killilea, M, Kirwan, J, Klockaerts, C, Kovac, V, Liew, A, Lippens, C, Macchi, F, Manenti, L, Margari, F, Margari, L, Martinelli, P, Mcfadden, L, Menghini, D, Miller, S, Monzani, E, Morini, G, Mutafov, T, O'Hara, L, Negrinotti, C, Nelis, E, Neri, F, Nikolova, P, Nossa, M, Cataldo, M, Noterdaeme, M, Operto, F, Panaro, V, Pastore, A, Pemmaraju, V, Pepermans, A, Petruzzelli, M, Presicci, A, Prigent, C, Rinaldi, F, Riva, E, Roekens, A, Rogers, B, Ronzini, P, Sakar, V, Salvetti, S, Martinelli, O, Sandhu, T, Schepker, R, Siviero, M, Slowik, M, Smyth, C, Conti, P, Spadone, M, Starace, F, Stoppa, P, Tansini, L, Toselli, C, Trabucchi, G, Tubito, M, van Dam, A, van Gutschoven, H, van West, D, Vanni, F, Vannicola, C, Varuzza, C, Varvara, P, Ventura, P, Vicari, S, Vicini, S, von Bentzel, C, Wells, P, Williams, B, Zabarella, M, Zamboni, A, Zanetti, E, Gerritsen S. E., van Bodegom L. S., Dieleman G. C., Overbeek M. M., Verhulst F. C., Wolke D., Rizopoulos D., Appleton R., van Amelsvoort T. A. M. J., Bodier Rethore C., Bonnet-Brilhault F., Charvin I., Da Fonseca D., Davidovic N., Dodig-Curkovic K., Ferrari A., Fiori F., Franic T., Gatherer C., de Girolamo G., Heaney N., Hendrickx G., Jardri R., Kolozsvari A., Lida-Pulik H., Lievesley K., Madan J., Mastroianni M., Maurice V., McNicholas F., Nacinovich R., Parenti A., Paul M., Purper-Ouakil D., Rivolta L., de Roeck V., Russet F., Saam M. C., Sagar-Ouriaghli I., Santosh P. J., Sartor A., Schulze U. M. E., Scocco P., Signorini G., Singh S. P., Singh J., Speranza M., Stagi P., Stagni P., Street C., Tah P., Tanase E., Tremmery S., Tuffrey A., Tuomainen H., Walker L., Wilson A., Maras A., Adams L., Allibrio G., Armando M., Aslan S., Baccanelli N., Balaudo M., Bergamo F., Bertani A., Berriman J., Boon A., Braamse K., Breuninger U., Buttiglione M., Buttle S., Schandrin A., Cammarano M., Canaway A., Cantini F., Cappellari C., Carenini M., Carra G., Ferrari C., Chianura K., Coleman P., Colonna A., Conese P., Costanzo R., Daffern C., Danckaerts M., de Giacomo A., Ermans J. -P., Farmer A., Fegert J. M., Ferrari S., Galea G., Gatta M., Gheza E., Goglia G., Grandetto M. R., Griffin J., Levi F. M., Humbertclaude V., Ingravallo N., Invernizzi R., Kelly C., Killilea M., Kirwan J., Klockaerts C., Kovac V., Liew A., Lippens C., Macchi F., Manenti L., Margari F., Margari L., Martinelli P., McFadden L., Menghini D., Miller S., Monzani E., Morini G., Mutafov T., O'Hara L., Negrinotti C., Nelis E., Neri F., Nikolova P., Nossa M., Cataldo M. G., Noterdaeme M., Operto F., Panaro V., Pastore A., Pemmaraju V., Pepermans A., Petruzzelli M. G., Presicci A., Prigent C., Rinaldi F., Riva E., Roekens A., Rogers B., Ronzini P., Sakar V., Salvetti S., Martinelli O., Sandhu T., Schepker R., Siviero M., Slowik M., Smyth C., Conti P., Spadone M. A., Starace F., Stoppa P., Tansini L., Toselli C., Trabucchi G., Tubito M., van Dam A., van Gutschoven H., van West D., Vanni F., Vannicola C., Varuzza C., Varvara P., Ventura P., Vicari S., Vicini S., von Bentzel C., Wells P., Williams B., Zabarella M., Zamboni A., and Zanetti E.

Abstract

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

Published
2022

5. Healthcare costs for young people transitioning the boundary between child/adolescent and adult mental health services in seven European countries:results from the MILESTONE study

Author

Canaway, A, Appleton, R, van Bodegom, L, Dieleman, G, Franic, T, Gerritsen, S, de Girolamo, G, Maras, A, Mcnicholas, F, Overbeek, M, Paul, M, Purper-Ouakil, D, Santosh, P, Schulze, U, Singh, SP, Street, C, Tah, P, Tremmery, B, Tuomainen, H, Verhulst, FC, Wolke, D, Madan, J, Canaway, A, Appleton, R, van Bodegom, L, Dieleman, G, Franic, T, Gerritsen, S, de Girolamo, G, Maras, A, Mcnicholas, F, Overbeek, M, Paul, M, Purper-Ouakil, D, Santosh, P, Schulze, U, Singh, SP, Street, C, Tah, P, Tremmery, B, Tuomainen, H, Verhulst, FC, Wolke, D, and Madan, J

Abstract

Background The boundary between services for children and adolescents and adults has been identified as problematic for young people with mental health problems. Aims To examine the use and cost of healthcare for young people engaged in mental healthcare before and after the child/adolescent and adult service boundary. Method Data from 772 young people in seven European countries participating in the MILESTONE trial were analysed. We analysed and costed healthcare resources used in the 6-month period before and after the service boundary. Results The proportion of young people engaging with healthcare services fell substantially after crossing the service boundary (associated costs €7761 pre-boundary v. €3376 post-boundary). Pre-boundary, the main cost driver was in-patient care (approximately 50%), whereas post-boundary costs were more evenly spread between services; cost reductions were correlated with pre-boundary in-patient care. Severity was associated with substantially higher costs pre- and post-boundary, and those who were engaged specifically with mental health services after the service boundary accrued the greatest healthcare costs post-service boundary. Conclusions Costs of healthcare are large in this population, but fall considerably after transition, particularly for those who were most severely ill. In part, this is likely to reflect improvement in the mental health of young people. However, qualitative evidence from the MILESTONE study suggests that lack of capacity in adult services and young people's disengagement with formal mental health services post-transition are contributing factors. Long-term data are needed to assess the adverse long-term effects on costs and health of this unmet need and disengagement.

Published
2023

6. The importance of clinicians' and parents' awareness of suicidal behaviour in adolescents reaching the upper age limit of their mental health services in Europe

Author

van Bodegom, L, Gerritsen, S, Dieleman, G, Overbeek, M, de Girolamo, G, Scocco, P, Hillegers, M, Wolke, D, Rizopoulos, D, Appleton, R, Conti, P, Franić, T, Margari, F, Madan, J, Mcnicholas, F, Nacinovich, R, Pastore, A, Paul, M, Purper-Ouakil, D, Saam, M, Santosh, P, Sartor, A, Schulze, U, Signorini, G, Singh, S, Street, C, Tah, P, Tanase, E, Tremmery, S, Tuomainen, H, Maras, A, van Bodegom, Larissa S, Gerritsen, Suzanne E, Dieleman, Gwendolyn C, Overbeek, Mathilde M, de Girolamo, Giovanni, Scocco, Paolo, Hillegers, Manon H J, Wolke, Dieter, Rizopoulos, Dimitris, Appleton, Rebecca, Conti, Patrizia, Franić, Tomislav, Margari, Francesco, Madan, Jason, McNicholas, Fiona, Nacinovich, Renata, Pastore, Adriana, Paul, Moli, Purper-Ouakil, Diane, Saam, Melanie C, Santosh, Paramala J, Sartor, Anne, Schulze, Ulrike M E, Signorini, Giulia, Singh, Swaran P, Street, Cathy, Tah, Priya, Tanase, Elena, Tremmery, Sabine, Tuomainen, Helena, Maras, Athanasios, van Bodegom, L, Gerritsen, S, Dieleman, G, Overbeek, M, de Girolamo, G, Scocco, P, Hillegers, M, Wolke, D, Rizopoulos, D, Appleton, R, Conti, P, Franić, T, Margari, F, Madan, J, Mcnicholas, F, Nacinovich, R, Pastore, A, Paul, M, Purper-Ouakil, D, Saam, M, Santosh, P, Sartor, A, Schulze, U, Signorini, G, Singh, S, Street, C, Tah, P, Tanase, E, Tremmery, S, Tuomainen, H, Maras, A, van Bodegom, Larissa S, Gerritsen, Suzanne E, Dieleman, Gwendolyn C, Overbeek, Mathilde M, de Girolamo, Giovanni, Scocco, Paolo, Hillegers, Manon H J, Wolke, Dieter, Rizopoulos, Dimitris, Appleton, Rebecca, Conti, Patrizia, Franić, Tomislav, Margari, Francesco, Madan, Jason, McNicholas, Fiona, Nacinovich, Renata, Pastore, Adriana, Paul, Moli, Purper-Ouakil, Diane, Saam, Melanie C, Santosh, Paramala J, Sartor, Anne, Schulze, Ulrike M E, Signorini, Giulia, Singh, Swaran P, Street, Cathy, Tah, Priya, Tanase, Elena, Tremmery, Sabine, Tuomainen, Helena, and Maras, Athanasios

Abstract

Background: To study clinicians' and parents' awareness of suicidal behaviour in adolescents reaching the upper age limit of their Child and Adolescent Mental Health Service (CAMHS) and its association with mental health indicators, transition recommendations and mental health service (MHS) use. Methods: 763 CAMHS users from eight European countries were assessed using multi-informant and standardised assessment tools at baseline and nine months follow-up. Separate ANCOVA's and pairwise comparisons were conducted to assess whether clinicians' and parents' awareness of young people's suicidal behaviour were associated with mental health indicators, clinician's recommendations to continue treatment and MHS use at nine months follow-up. Results: 53.5 % of clinicians and 56.9 % of parents were unaware of young people's self-reported suicidal behaviour at baseline. Compared to those whose clinicians/parents were aware, unawareness was associated with a 72–80 % lower proportion of being recommended to continue treatment. Self-reported mental health problems at baseline were comparable for young people whose clinicians and parents were aware and unaware of suicidal behaviour. Clinicians' and parents' unawareness were not associated with MHS use at follow-up. Limitations: Aspects of suicidal behaviour, such as suicide ideation, -plans and -attempts, could not be distinguished. Few young people transitioned to Adult Mental Health Services (AMHS), therefore power to study factors associated with AMHS use was limited. Conclusion: Clinicians and parents are often unaware of suicidal behaviour, which decreases the likelihood of a recommendation to continue treatment, but does not seem to affect young people's MHS use or their mental health problems.

Published
2023

9. ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016

Author

Bos, L., Schouten, L., van Vught, L., Wiewel, M., Ong, D., Cremer, O., Artigas, A., Martin-Loeches, I., Hoogendijk, A., van der Poll, T., Horn, J., Juffermans, N., Schultz, M., de Prost, N., Pham, T., Carteaux, G., Dessap, A. Mekontso, Brun-Buisson, C., Fan, E., Bellani, G., Laffey, J., Mercat, A., Brochard, L., Maitre, B., Howells, P. A., Thickett, D. R., Knox, C., Park, D. P., Gao, F., Tucker, O., Whitehouse, T., McAuley, D. F., Perkins, G. D., Pham, T., Laffey, J., Bellani, G., Fan, E., Pisani, L., Roozeman, J. P., Simonis, F. D., Giangregorio, A., Schouten, L. R., Van der Hoeven, S. M., Horn, J., Neto, A. Serpa, Festic, E., Dondorp, A. M., Grasso, S., Bos, L. D., Schultz, M. J., Koster-Brouwer, M., Verboom, D., Scicluna, B., van de Groep, K., Frencken, J., Schultz, M., van der Poll, T., Bonten, M., Cremer, O., Ko, J. I., Kim, K. S., Suh, G. J., Kwon, W. Y., Kim, K., Shin, J. H., Ranzani, O. T., Prina, E., Menendez, R., Ceccato, A., Mendez, R., Cilloniz, C., Gabarrus, A., Ferrer, M., Torres, A., Urbano, A., Zhang, L. A., Swigon, D., Pike, F., Parker, R. S., Clermont, G., Scheer, C., Kuhn, S. O., Modler, A., Vollmer, M., Fuchs, C., Hahnenkamp, K., Rehberg, S., Gründling, M., Taggu, A., Darang, N., Öveges, N., László, I., Tánczos, K., Németh, M., Lebák, G., Tudor, B., Érces, D., Kaszaki, J., Huber, W., Trásy, D., Molnár, Z., Ferrara, G., Edul, V. S. Kanoore, Canales, H. S., Martins, E., Canullán, C., Murias, G., Pozo, M. O., Eguillor, J. F. Caminos, Buscetti, M. G., Ince, C., Dubin, A., Aya, H. D., Rhodes, A., Fletcher, N., Grounds, R. M., Cecconi, M., Jacquet-Lagrèze, M., Riche, M., Schweizer, R., Portran, P., Fornier, W., Lilot, M., Neidecker, J., Fellahi, J. L., Escoresca-Ortega, A., Gutiérrez-Pizarraya, A., Charris-Castro, L., Corcia-Palomo, Y., Fernandez-Delgado, E., Garnacho-Montero, J., Roger, C., Muller, L., Elotmani, L., Lipman, J., Lefrant, J. Y., Roberts, J. 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W., Kaymak, C., Okumus, N., Sari, A., Erdogdu, B., Aksun, S., Basar, H., Ozcan, A., Ozcan, N., Oztuna, D., Malmgren, J. A., Lundin, S., Torén, K., Eckerström, M., Wallin, A., Waldenström, A. C., Riccio, F. C., Pogson, D., Antonio, A. C. P., Leivas, A. F., Kenji, F., James, E., Morgan, P., Carroll, G., Gemmell, L., MacKay, A., Wright, C., Ballantyne, J., Jonnada, S., Gerrard, C. S., Jones, N., Salciccioli, J. D., Marshall, D. C., Komorowski, M., Hartley, A., Sykes, M. C., Goodson, R., Shalhoub, J., Villanueva, J. R. Fernández, Garda, R. Fernández, Lago, A. M. López, Ruiz, E. Rodríguez, Vaquero, R. Hernández, Rodríguez, C. Galbán, Pérez, E. Varo, Hilasque, C., Oliva, I., Sirgo, G., Martin, M. C., Olona, M., Gilavert, M. C., Bodí, M., Ebm, C., Aggarwal, G., Huddart, S., Quiney, N., Cecconi, M., Fernandes, S. M., Silva, J. Santos, Gouveia, J., Silva, D., Marques, R., Bento, H., Alvarez, A., Silva, Z. Costa, Diaz, D. Díaz, Martínez, M. Villanova, Herrejon, E. Palencia, de la Gandara, A. Martinez, Gonzalo, G., Lopez, M. A., de Gopegui Miguelena, P. Ruíz, Matilla, C. I. Bernal, Chueca, P. Sánchez, Longares, M. D. C. Rodríguez, Abril, R. Ramos, Aguilar, A. L. Ruíz, de Murillas, R. Garrido López, Fernández, R. Fernández, Laborías, P. Morales, Castellanos, M. A. Díaz, Laborías, M. E. Morales, Cho, J., Kim, J., Park, J., Woo, S., West, T., Powell, E., Rimmer, A., Orford, C., Jones, N., Williams, J., Matilla, C. I. Bernal, de Gopegui Miguelena, P. Ruiz, Chueca, P. Sánchez, Abril, R. Ramos, Longares, M. D. C. Rodríguez, Aguilar, A. L. Ruíz, de Murillas, R. Garrido López, Bourne, R. S., Shulman, R., Tomlin, M., Mills, G. H., Borthwick, M., Berry, W., Huertas, D. García, Manzano, F., Villagrán-Ramírez, F., Ruiz-Perea, A., Rodríguez-Mejías, C., Santiago-Ruiz, F., Colmenero-Ruiz, M., König, C., Matt, B., Kortgen, A., Hartog, C. S., Wong, A., Balan, C., Barker, G., Srisawat, N., Peerapornratana, S., Laoveeravat, P., Tachaboon, S., Eiam-ong, S., Paratz, J., Kayambu, G., Boots, R., Arzapalo, M. F. Aguilar, Vlasenko, R., Gromova, E., Loginov, S., Kiselevskiy, M., Dolgikova, Y., Tang, K. B., Chau, C. M., Lam, K. N., Gil, E., Suh, G. Y., Park, C. M., Park, J., Chung, C. R., Lee, C. T., Chao, A., Shih, P. Y., Chang, Y. F., Lai, C. H., Hsu, Y. C., Yeh, Y. C., Cheng, Y. J., Colella, V., Zarrillo, N., D’Amico, M., Forfori, F., Pezza, B., Laddomada, T., Beltramelli, V., Pizzaballa, M. L., Doronzio, A., Balicco, B., Kiers, D., van der Heijden, W., Gerretsen, J., de Mast, Q., el Messaoudi, S., Rongen, G., Gomes, M., Kox, M., Pickkers, P., Riksen, N. P., Kashiwagi, Y., Okada, M., Hayashi, K., Inagaki, Y., Fujita, S., Nakamae, M. N., Kang, Y. R., Souza, R. B., Liberatore, A. M. A., Koh, I. H. J., Blet, A., Sadoune, M., Lemarié, J., Bihry, N., Bern, R., Polidano, E., Merval, R., Launay, J. M., Lévy, B., Samuel, J. L., Mebazaa, A., Hartmann, J., Harm, S., and Weber, V.

Published
2016
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16. Implementation, Adoption, and Perceptions of Telemental Health During the COVID-19 Pandemic: Systematic Review.

Author

Appleton, R, Williams, J, Vera San Juan, N, Needle, JJ, Schlief, M, Jordan, H, Sheridan Rains, L, Goulding, L, Badhan, M, Roxburgh, E, Barnett, P, Spyridonidis, S, Tomaskova, M, Mo, J, Harju-Seppänen, J, Haime, Z, Casetta, C, Papamichail, A, Lloyd-Evans, B, Simpson, A, Sevdalis, N, Gaughran, F, Johnson, S, Appleton, R, Williams, J, Vera San Juan, N, Needle, JJ, Schlief, M, Jordan, H, Sheridan Rains, L, Goulding, L, Badhan, M, Roxburgh, E, Barnett, P, Spyridonidis, S, Tomaskova, M, Mo, J, Harju-Seppänen, J, Haime, Z, Casetta, C, Papamichail, A, Lloyd-Evans, B, Simpson, A, Sevdalis, N, Gaughran, F, and Johnson, S

Abstract

BACKGROUND: Early in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health and to debates on its future use in routine mental health care. OBJECTIVE: To investigate the adoption and impacts of telemental health approaches during the COVID-19 pandemic, and facilitators and barriers to optimal implementation. METHODS: Four databases (PubMed, PsycINFO, CINAHL, and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesized using framework synthesis. RESULTS: A total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified. CONCLUSIONS: Implementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these. TRIAL REGISTRA

Published
2021

20. A quantitative framework to inform extrapolation decisions in children

Author

Wadsworth, I., Hampson, L.V., Jaki, T., Sills, G.J., Marson, A.G., Appleton, R., Wadsworth, I., Hampson, L.V., Jaki, T., Sills, G.J., Marson, A.G., and Appleton, R.

Abstract

When developing a new medicine for children, the potential to extrapolate from adult efficacy data is well recognized. However, significant assumptions about the similarity of adults and children are needed for extrapolations to be biologically plausible. One such assumption is that of similar exposure–response (E–R‐) relationships. Motivated by applications to antiepileptic drug development, we consider how data that are available from existing trials of adults and adolescents can be used to quantify prior uncertainty about whether E–R‐relationships are similar in adults and younger children. A Bayesian multivariate meta‐analytic model is fitted to existing E–R‐data and adjusted for external biases that arise because these data are not perfectly relevant to the comparison of interest. We propose a strategy for eliciting expert prior opinion on external biases. From the bias‐adjusted meta‐analysis, we derive prior distributions quantifying our uncertainty about the degree of similarity between E–R‐relationships for adults and younger children. Using these we calculate the prior probability that average pharmacodynamic responses in adults and younger children, both on placebo and at an effective concentration, are sufficiently similar to justify a complete extrapolation of efficacy data. A simulation study is performed to evaluate the operating characteristics of the approach proposed.

Published
2020

21. Validation of the Transition Readiness and Appropriateness Measure (TRAM) for the Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare in Europe (MILESTONE) study

Author

Santosh, P. (Paramala), Singh, J. (Jatinder), Adams, L. (Laura), Mastroianni, M. (Mathilde), Heaney, N. (Natalie), Lievesley, K. (Kate), Sagar-Ouriaghli, I. (Ilyas), Allibrio, G. (Giovanni), Appleton, R. (Rebecca), Davidović, N. (Nikolina), de Girolamo, G. (Giovanni), Dieleman, G.C. (Gwen), Dodig-Ćurković, K. (Katarina), Franić, T. (Tomislav), Gatherer, C. (Charlotte), Gerritsen, S.E. (Suzanne), Gheza, E. (Elisa), Madan, J. (Jason), Manenti, L. (Lidia), Maras, A. (Athanasios), Margari, F. (Francesco), McNicholas, F. (Fiona), Pastore, A. (Adriana), Paul, M. (Moli), Purper-Ouakil, D. (Diane), Rinaldi, F. (Francesco), Sakar, V. (Vehbi), Schulze, U. (Ulrike), Signorini, G. (Giulia), Street, C. (Cathy), Tah, P. (Priya), Tremmery, S. (Sabine), Tuffrey, A. (Amanda), Tuomainen, H. (Helena), Verhulst, F.C. (Frank), Warwick, J. (Jane), Wilson, A. (Anna), Wolke, D. (Dieter), Fiori, F. (Federico), Singh, S.P. (Swaran), Santosh, P. (Paramala), Singh, J. (Jatinder), Adams, L. (Laura), Mastroianni, M. (Mathilde), Heaney, N. (Natalie), Lievesley, K. (Kate), Sagar-Ouriaghli, I. (Ilyas), Allibrio, G. (Giovanni), Appleton, R. (Rebecca), Davidović, N. (Nikolina), de Girolamo, G. (Giovanni), Dieleman, G.C. (Gwen), Dodig-Ćurković, K. (Katarina), Franić, T. (Tomislav), Gatherer, C. (Charlotte), Gerritsen, S.E. (Suzanne), Gheza, E. (Elisa), Madan, J. (Jason), Manenti, L. (Lidia), Maras, A. (Athanasios), Margari, F. (Francesco), McNicholas, F. (Fiona), Pastore, A. (Adriana), Paul, M. (Moli), Purper-Ouakil, D. (Diane), Rinaldi, F. (Francesco), Sakar, V. (Vehbi), Schulze, U. (Ulrike), Signorini, G. (Giulia), Street, C. (Cathy), Tah, P. (Priya), Tremmery, S. (Sabine), Tuffrey, A. (Amanda), Tuomainen, H. (Helena), Verhulst, F.C. (Frank), Warwick, J. (Jane), Wilson, A. (Anna), Wolke, D. (Dieter), Fiori, F. (Federico), and Singh, S.P. (Swaran)

Abstract

OBJECTIVE: Young people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16-18 years of age in Europe). The objective of this study was to develop and

Published
2020
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22. Validation of the Transition Readiness and Appropriateness Measure (TRAM) for the Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare in Europe (MILESTONE) study

Author

Santosh, P, Singh, J, Adams, L, Mastroianni, M, Heaney, N, Lievesley, K, Sagar-Ouriaghli, I, Allibrio, G, Appleton, R, Davidovic, N, de Girolamo, G, Dieleman, Gwen, Dodig-Curkovic, K, Franic, T, Gatherer, C, Gerritsen, Suzanne, Gheza, E, Madan, J, Manenti, L, Maras, Athanasios, Margari, F, McNicholas, F, Pastore, A, Paul, M, Purper-Ouakil, D, Rinaldi, F, Sakar, V, Schulze, U, Signorini, G, Street, C, Tah, P, Tremmery, S, Tuffrey, A, Tuomainen, H, Verhulst, Frank, Warwick, J, Wilson, A, Wolke, D, Fiori, F, Singh, S, Santosh, P, Singh, J, Adams, L, Mastroianni, M, Heaney, N, Lievesley, K, Sagar-Ouriaghli, I, Allibrio, G, Appleton, R, Davidovic, N, de Girolamo, G, Dieleman, Gwen, Dodig-Curkovic, K, Franic, T, Gatherer, C, Gerritsen, Suzanne, Gheza, E, Madan, J, Manenti, L, Maras, Athanasios, Margari, F, McNicholas, F, Pastore, A, Paul, M, Purper-Ouakil, D, Rinaldi, F, Sakar, V, Schulze, U, Signorini, G, Street, C, Tah, P, Tremmery, S, Tuffrey, A, Tuomainen, H, Verhulst, Frank, Warwick, J, Wilson, A, Wolke, D, Fiori, F, and Singh, S

Published
2020

23. 1.6 Tbps Silicon Photonics Integrated Circuit and 800 Gbps Photonic Engine for Switch Co-Packaging Demonstration

Author

Fathololoumi, Saeed, primary, Hui, David, additional, Jadhav, Susheel, additional, Chen, Jian, additional, Nguyen, Kimchau, additional, Sakib, M.N., additional, Li, Z., additional, Mahalingam, Hari, additional, Amiralizadeh, Siamak, additional, Tang, Nelson N., additional, Potluri, Harinadh, additional, Montazeri, Mohammad, additional, Frish, Harel, additional, Defrees, Reece A., additional, Seibert, Christopher, additional, Krichevsky, Alexander, additional, Doylend, Jonathan K., additional, Heck, John, additional, Venables, R., additional, Dahal, A., additional, Awujoola, A., additional, Vardapetyan, A., additional, Kaur, Guneet, additional, Cen, Min, additional, Kulkarni, Vishnu, additional, Islam, Syed S., additional, Spreitzer, R. L., additional, Garag, S., additional, Alduino, A. C., additional, Chiou, RK, additional, Kamyab, L., additional, Gupta, S., additional, Xie, B., additional, Appleton, R. S., additional, Hollingsworth, S., additional, McCargar, S., additional, Akulova, Y., additional, Brown, K. M., additional, Jones, R., additional, Zhu, Daniel, additional, Liljeberg, Thomas, additional, and Liao, Ling, additional

Published
2021
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25. Febrile seizures: An update

Author

Waruiru, C. and Appleton, R.

Subjects
Febrile convulsions -- Research, Infants (Newborn) -- Diseases, Infants (Newborn) -- Research, Children -- Diseases, Children -- Research
Published
2004

32. Cerebral palsy: not always what it seems. (Community child health, public health and epidemiology)

Author

Gupta, R and Appleton, R E.

Subjects
Cerebral palsied children -- Care and treatment -- Physiological aspects, Cerebral palsy -- Physiological aspects -- Care and treatment, Family and marriage, Health, Care and treatment, Physiological aspects
Abstract

Cerebral palsy (CP) is an umbrella term that defines a group of non-progressive, but often changing, syndromes of motor impairment secondary to lesions or anomalies of the brain arising in [...]

Published
2001

36. Genetic regulation of gene expression in the epileptic human hippocampus

Author

Mirza, N, Appleton, R, Burn, S, du, Plessis D, Duncan, R, Farah, JO, Feenstra, B, Hviid, A, Josan, V, Mohanraj, R, Shukralla, A, Sills, GJ, Marson, AG, and Pirmohamed, M

Subjects
Epilepsy, Gene Expression Profiling, Association Studies Articles, Quantitative Trait Loci, Brain, Gene Expression, Hippocampus, Polymorphism, Single Nucleotide, Seizures, Febrile, Gene Expression Regulation, Risk Factors, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocampal tissue to include not only normal (n = 22) but also epileptic (n = 22) samples. We demonstrate that disease-associated variants from an epilepsy GWAS meta-analysis and a febrile seizures (FS) GWAS are significantly more enriched with epilepsy-eQTLs than with normal hippocampal eQTLs from two larger independent published studies. In contrast, GWAS meta-analyses of two other brain diseases associated with hippocampal pathology (Alzheimer’s disease and schizophrenia) are more enriched with normal hippocampal eQTLs than with epilepsy-eQTLs. These observations suggest that an eQTL analysis that includes disease-affected brain tissue is advantageous for detecting additional risk SNPs for the afflicting and closely related disorders, but not for distinct diseases affecting the same brain regions. We also show that epilepsy eQTLs are enriched within epilepsy-causing genes: an epilepsy cis-gene is significantly more likely to be a causal gene for a Mendelian epilepsy syndrome than to be a causal gene for another Mendelian disorder. Epilepsy cis-genes, compared to normal hippocampal cis-genes, are more enriched within epilepsy-causing genes. Hence, we utilize the epilepsy eQTL data for the functional interpretation of epilepsy disease-risk variants and, thereby, highlight novel potential causal genes for sporadic epilepsy. In conclusion, an epilepsy-eQTL analysis is superior to normal hippocampal tissue eQTL analyses for identifying the variants and genes underlying epilepsy.

Published
2017

47. Training of adult psychiatrists and child and adolescent psychiatrists in europe

Author

Singh, S.P. (Swaran), Madan, J. (Jason), Warwick, J. (Jane), Wolke, D. (Dieter), Appleton, R. (Rebecca), Canaway, A. (Alastair), Griffin, J.D. (James), De Girolamo, G. (Giovanni), Santosh, P. (Paramala), Sagar-Ouriaghli, I. (Ilyas), Heaney, N. (Natalie), Maurice, V. (Virginie), Van Bodegom, L. (Larissa), Overbeek, M. (Mathilde), Kooymans, E. (Esther), Schulze, U. (Ulrike), Saam, M. (Melanie), Breuninger, U. (Ulrike), Gronostaj, A. (Aleksandra), Franić, T. (Tomislav), Davidović, N. (Nikolina), Verhulst, F.C. (Frank), Gerritsen, S.E. (Suzanne), Lievesley, K. (Kate), Tuffrey, A. (Amanda), Wilson, A. (Anna), Gatherer, C. (Charlotte), Walker, L. (Leanne), Russet, F. (Frederick), Humbertclaude, V. (Veronique), Dieleman, G.C. (Gwen), Dodig-Ćurković, K. (Katarina), Hendrickx, G. (Gaelle), Kovač, V. (Vlatka), McNicholas, F. (Fiona), Maras, A. (Athanasios), Paramala, S. (Santosh), Paul, M. (Moli), Schulze, U.M.E. (Ulrike M. E.), Signorini, G. (Giulia), Street, C. (Cathy), Tah, P. (Priya), Tuomainen, H. (Helena), Singh, S.P. (Swaran P.), Tremmery, S. (Sabine), Purper-Ouakil, D. (Diane), Singh, S.P. (Swaran), Madan, J. (Jason), Warwick, J. (Jane), Wolke, D. (Dieter), Appleton, R. (Rebecca), Canaway, A. (Alastair), Griffin, J.D. (James), De Girolamo, G. (Giovanni), Santosh, P. (Paramala), Sagar-Ouriaghli, I. (Ilyas), Heaney, N. (Natalie), Maurice, V. (Virginie), Van Bodegom, L. (Larissa), Overbeek, M. (Mathilde), Kooymans, E. (Esther), Schulze, U. (Ulrike), Saam, M. (Melanie), Breuninger, U. (Ulrike), Gronostaj, A. (Aleksandra), Franić, T. (Tomislav), Davidović, N. (Nikolina), Verhulst, F.C. (Frank), Gerritsen, S.E. (Suzanne), Lievesley, K. (Kate), Tuffrey, A. (Amanda), Wilson, A. (Anna), Gatherer, C. (Charlotte), Walker, L. (Leanne), Russet, F. (Frederick), Humbertclaude, V. (Veronique), Dieleman, G.C. (Gwen), Dodig-Ćurković, K. (Katarina), Hendrickx, G. (Gaelle), Kovač, V. (Vlatka), McNicholas, F. (Fiona), Maras, A. (Athanasios), Paramala, S. (Santosh), Paul, M. (Moli), Schulze, U.M.E. (Ulrike M. E.), Signorini, G. (Giulia), Street, C. (Cathy), Tah, P. (Priya), Tuomainen, H. (Helena), Singh, S.P. (Swaran P.), Tremmery, S. (Sabine), and Purper-Ouakil, D. (Diane)

Abstract

Background: Profound clinical, conceptual and ideological differences between child and adult mental health service models contribute to transition-related discontinuity of care. Many of these may be related to psychiatry training. Methods: A systematic review on General Adult Psychiatry (GAP) and Child and Adult Psychiatry (CAP) training in Europe, with a particular focus on transition as a theme in GAP and CAP training. Results: Thirty-four full-papers, six abstracts and seven additional full text documents were identified. Important variations between countries were found across several domains including assessment of trainees, clinical and educational supervision, psychotherapy training and continuing medical education. Three models of training were identified: i) a generalist common training programme; ii) totally separate training programmes; iii) mixed types. Only two national training programs (UK and Ireland) were identified to have addressed transition as a topic, both involving CAP exclusively. Conclusion: Three models of training in GAP and CAP across Europe are identified, suggesting that the harmonization is not yet realised and a possible barrier to improving transitional care. Training in transition has only recently been considered. It is timely, topical and important to develop evidence-based training approaches on transitional care across Europe into both CAP and GAP training.

Published
2019
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