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1.
Epilepsia ; 65(5): 1394-1405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441332

RESUMO

OBJECTIVE: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic. METHODS: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs). RESULTS: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15). SIGNIFICANCE: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research.


Assuntos
COVID-19 , Epilepsia , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , Epilepsia/epidemiologia , Epilepsia/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Idoso , Adolescente , Criança , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , País de Gales/epidemiologia , Pré-Escolar , Estado Epiléptico/mortalidade , Estado Epiléptico/epidemiologia , Hospitalização/estatística & dados numéricos , Lactente , Pandemias , Serviço Hospitalar de Emergência/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/mortalidade , Idoso de 80 Anos ou mais
2.
Epilepsia ; 65(5): 1383-1393, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441374

RESUMO

OBJECTIVE: People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19. METHODS: We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios. RESULTS: There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78). SIGNIFICANCE: PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE.


Assuntos
COVID-19 , Epilepsia , Hospitalização , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Feminino , Masculino , Hospitalização/estatística & dados numéricos , Epilepsia/epidemiologia , Epilepsia/mortalidade , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , País de Gales/epidemiologia , Adulto Jovem , Fatores de Risco , Adolescente , Estudos de Coortes , Idoso de 80 Anos ou mais , Comorbidade , SARS-CoV-2
3.
J Clin Nurs ; 32(13-14): 3730-3745, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36494199

RESUMO

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.


Assuntos
COVID-19 , Epilepsia , Enfermeiras e Enfermeiros , Humanos , Pandemias , Estudos Retrospectivos , Papel do Profissional de Enfermagem , Pesquisa Qualitativa
4.
J Nurs Manag ; 30(8): 4262-4273, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36326612

RESUMO

AIM(S): The study aimed to test a model that examined the relationships between authentic leadership, psychological safety, work engagement and team effectiveness and subsequent effects of team effectiveness on job turnover intentions and nurse satisfaction with quality of care. BACKGROUND: Nurse leaders who exhibit authentic leadership have been shown to contribute to the development of healthy work environments. In workplaces with demonstrated authentic leadership, nurses are more engaged and have lower job turnover intentions. METHOD(S): A non-experimental, cross-sectional design was used to test the hypothesized model via structural equation modelling. A total of 456 nurses were included. RESULTS: Structural equation modelling analysis indicated a good fit for the hypothesized model. Authentic leadership had a positive, significant and direct relationship with team effectiveness, nurses' work engagement and psychological safety. Team effectiveness was found to be negatively related to job turnover intentions but positively related to nurse satisfaction with quality of care. CONCLUSION(S): Results of this study may help nursing leaders have a better understanding of the essential role of leadership style in increasing healthy work environments. IMPLICATIONS FOR NURSING MANAGEMENT: Applying authentic leadership style in nursing practice could help to reduce the shortage of nurses stemming from the high turnover intentions of nurses.


Assuntos
Liderança , Enfermeiras e Enfermeiros , Humanos , Arábia Saudita , Intenção , Análise de Classes Latentes , Estudos Transversais , Satisfação no Emprego , Enfermeiras e Enfermeiros/psicologia , Reorganização de Recursos Humanos , Satisfação Pessoal , Inquéritos e Questionários
5.
BMC Pregnancy Childbirth ; 21(1): 204, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711951

RESUMO

BACKGROUND: Premature delivery is among the leading causes of perinatal mortality and morbidity in developed societies, which is an important obstetrics problem. Maternal periodontitis is a prevalent condition that has been suspected to be associated with adverse pregnancy outcomes such as premature birth. However, there are still conflicting results about this possible relationship, therefore this study was designed to test the association between maternal periodontitis and premature birth. This study also provides information about a new screening tool recommended for use by nurses and midwives to screen for periodontal diseases during antenatal consultations in order to improve the health of mothers and children. METHODS: A retrospective case-control study was conducted at 12 health facilities in the Southern Province of Rwanda from February to August, 2018. A total of 555 women in the postpartum period were enrolled in the study. Cases and controls were enrolled in a ratio of 1:2; each enrolled case of preterm birth was followed by 2 unmatched control subjects that were next on the register and who delivered at term gestation. A total of 185 cases of preterm deliveries and 370 controls of term delivery were enrolled in the study. Multivariate regression analysis was used and the independent variables were hierarchically entered in three groups: The first group involved demographic variables that were put in the regression model as Step 1. The second group was made up of other potential risk factors that were placed in the regression model as the second step. Periodontitis was entered in the final regression step, as it was hypothesized as the main predictor variable. RESULTS: A statistically significant association was found between periodontitis and premature birth. Women who had periodontitis had 6 times the odds of giving birth to premature birth infants compared to women who had no periodontitis (OR: 6.360, 95% CI 3.9, 10.4). CONCLUSION: The study results indicate that periodontitis is strongly associated with premature birth. Preventive solutions including the use of a periodontitis screening tool for nurses and midwives during antenatal care consultations, are highly recommended.


Assuntos
Periodontite , Complicações na Gravidez , Nascimento Prematuro , Diagnóstico Pré-Natal/métodos , Medição de Risco , Adulto , Estudos de Casos e Controles , Correlação de Dados , Feminino , Humanos , Recém-Nascido Prematuro , Periodontite/diagnóstico , Periodontite/epidemiologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal/métodos , Melhoria de Qualidade/organização & administração , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Ruanda/epidemiologia
6.
Chemistry ; 26(1): 171-175, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31614052

RESUMO

Novel oxime-ether tethered cyclopropanes, when exposed to Yb(OTf)3 and heat, annulate to generate hydropyrrolo-oxazines products that can be taken to their respective pyrrolidines via hydrogenative N-O bond cleavage. The hydropyrrolo-oxazines are generated in a diastereoselective manner isolating the cis or trans product based on the temperature of the reaction. 20 examples of selective cis and trans hydropyrrolo-oxazines were generated in high yields by temperature control.

7.
Epilepsy Behav ; 103(Pt B): 106453, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31427266

RESUMO

Routinely collected data are a powerful research resource and offer the opportunity to further our understanding of epilepsy mortality and Sudden Unexpected Death in Epilepsy (SUDEP). The advantages of using routinely collected data include that it often covers whole populations, is already collected, and can be easily linked to other data sources. A significant disadvantage is the difficulty in obtaining accurate causes of death and correctly identifying cases of SUDEP. Using and linking data from epilepsy death registries can improve the quality of mortality data for research. Epilepsy prevalence, incidence, and mortality rates are associated with socioeconomic deprivation. Further research into understanding the link between deprivation and epilepsy mortality could lead to ways to reduce epilepsy mortality. This paper is for the Special Issue :Prevent 21: SUDEP Summit - Time to Listen.


Assuntos
Coleta de Dados/métodos , Disparidades em Assistência à Saúde/economia , Sistema de Registros , Fatores Socioeconômicos , Morte Súbita Inesperada na Epilepsia/epidemiologia , Epilepsia/economia , Epilepsia/epidemiologia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/tendências , Humanos , Fatores de Risco , Morte Súbita Inesperada na Epilepsia/prevenção & controle
8.
J Adv Nurs ; 76(9): 2359-2368, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32542730

RESUMO

AIMS: To: (a) identify the differences and similarities in the extrinsic and intrinsic factors that influence job satisfaction among nurses in urban and rural Ontario; and (b) determine the impact of job satisfaction on nurses' turnover intention among nurses working in rural and urban settings in Ontario. DESIGN: Cross-sectional correlational design was used for this study. METHODS: Data were collected between May 2019-July 2019 in southern Ontario. Participants (N=349) completed the Acute Care Nurses' Job Satisfaction Scale and The Anticipated Turnover Scale. A stratified sampling technique was used for recruiting the sample population and participants were given the option to respond either online or by mailed survey. RESULTS: There was no significant difference between rural and urban nurses in either overall job satisfaction level or turnover intention. Peer support/work conditions, quality of supervision, and achievement/job interest/responsibility were significant predictors of job satisfaction. There was a significant difference between rural and urban nurses in terms of satisfaction from benefits and job security and the nurses' job satisfaction levels correlated negatively with their turnover intention. CONCLUSION: Several extrinsic and intrinsic factors are associated with nurses' job satisfaction in rural and urban settings. Developing strategies that improve satisfaction by modulating these specific factors may improve nurses' job satisfaction and reduce turnover. IMPACT: This study discussed how working in a rural or urban hospital may affect nurses' job satisfaction and turnover intention. The findings can help in improving nurses' job satisfaction and inform workforce planning to increase nurses' retention.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Estudos Transversais , Humanos , Satisfação no Emprego , Ontário , Reorganização de Recursos Humanos , Inquéritos e Questionários
9.
J Adv Nurs ; 76(4): 963-979, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31840301

RESUMO

AIMS: This review aimed to systematically assess the findings of primary studies to identify the factors associated with nurse job satisfaction in rural and urban contexts while analysing the findings according to Herzberg's theory. BACKGROUND: While there is evidence linking several factors to nurses' job satisfaction, gaps still exist in understanding the differences between factors affecting job satisfaction for nurses working in rural and urban settings. DESIGN: Systematic review with narrative summary. DATA SOURCES: Six databases were used to identify original studies that discuss the factors associated with the nurse's job satisfaction between 1998-2018. REVIEW METHODS: Two authors independently reviewed each study using the Joanna Briggs Institute's critical appraisal checklists. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to report and examine the study biases systematically. RESULTS: A total of 38 studies were selected for this review. Physical working environment and authority and freedom were the most frequently reported factors associated with nurses' job satisfaction. Several extrinsic, intrinsic, personal, and community factors were also found to be associated with nurses' job satisfaction. Urban studies tended to focus on extrinsic factors, whereas there was more balance between the two sets of factors in rural studies. CONCLUSION: Both intrinsic and extrinsic factors play an essential role in nurses' job satisfaction. Future research should use more robust research methods and pay more attention to contrasting rural and urban contexts. Herzberg's theory can provide conceptual clarity when investigating the factors associated with nurses' job satisfaction. IMPACT: This review discussed the factors associated with nurses' job satisfaction in rural and urban settings. The findings linked several extrinsic and intrinsic factors to nurses' job satisfaction. Nursing management should search for the perfect blend of intrinsic and extrinsic factors based on nurses' needs and organizational commitment to improve nurses' job satisfaction.


Assuntos
Satisfação no Emprego , Recursos Humanos de Enfermagem Hospitalar/psicologia , Serviços de Saúde Rural , Serviços Urbanos de Saúde , Humanos
10.
Epilepsia ; 60(5): 818-829, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977115

RESUMO

OBJECTIVE: The true prevalence of epileptic seizures and epilepsy in 22q11.2 deletion syndrome (22q11.2DS) is unknown, because previous studies have relied on historical medical record review. Associations of epilepsy with other neurodevelopmental manifestations (eg, specific psychiatric diagnoses) remain unexplored. METHODS: The primary caregivers of 108 deletion carriers (mean age 13.6 years) and 60 control siblings (mean age 13.1 years) completed a validated epilepsy screening questionnaire. A subsample (n = 44) underwent a second assessment with interview, prolonged electroencephalography (EEG), and medical record and epileptologist review. Intelligence quotient (IQ), psychopathology, and other neurodevelopmental problems were examined using neurocognitive assessment and questionnaire/interview. RESULTS: Eleven percent (12/108) of deletion carriers had an epilepsy diagnosis (controls 0%, P = 0.004). Fifty-seven of the remaining 96 deletion carriers (59.4%) had seizures or seizurelike symptoms (controls 13.3%, 8/60, P < 0.001). A febrile seizure was reported for 24.1% (26/107) of cases (controls 0%, P < 0.001). One deletion carrier with a clinical history of epilepsy was diagnosed with an additional type of unprovoked seizure during the second assessment. One deletion carrier was newly diagnosed with epilepsy, and two more with possible nonmotor absence seizures. A positive screen on the epilepsy questionnaire was more likely in deletion carriers with lower performance IQ (odds ratio [OR] 0.96, P = 0.018), attention-deficit/hyperactivity disorder (ADHD) (OR 3.28, P = 0.021), autism symptoms (OR 3.86, P = 0.004), and indicative motor coordination disorder (OR 4.56, P = 0.021). SIGNIFICANCE: Even when accounting for deletion carriers diagnosed with epilepsy, reports of seizures and seizurelike symptoms are common. These may be "true" epileptic seizures in some cases, which are not recognized during routine clinical care. Febrile seizures were far more common in deletion carriers compared to known population risk. A propensity for seizures in 22q11.2DS was associated with cognitive impairment, psychopathology, and motor coordination problems. Future research is required to determine whether this reflects common neurobiologic risk pathways or is a consequence of recurrent seizures.


Assuntos
Síndrome de DiGeorge/complicações , Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Convulsões/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Criança , Síndrome de DiGeorge/epidemiologia , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , Transtornos das Habilidades Motoras/epidemiologia , Transtornos das Habilidades Motoras/genética , Transtornos do Neurodesenvolvimento/epidemiologia , Prevalência , Convulsões/epidemiologia , Convulsões/fisiopatologia , Convulsões Febris/epidemiologia , Convulsões Febris/genética , Convulsões Febris/fisiopatologia , Sensibilidade e Especificidade , Inquéritos e Questionários , Reino Unido/epidemiologia , Escalas de Wechsler , Adulto Jovem
11.
Brain ; 141(3): 698-712, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365063

RESUMO

Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria.


Assuntos
Mutação/genética , Proteínas do Tecido Nervoso/genética , Polimicrogiria/genética , Receptores de N-Metil-D-Aspartato/genética , Animais , Criança , Pré-Escolar , Análise Mutacional de DNA , Agonistas de Aminoácidos Excitatórios/farmacologia , Saúde da Família , Feminino , Ácido Glutâmico/farmacologia , Glicina/metabolismo , Glicina/farmacologia , Células HEK293 , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Potenciais da Membrana/genética , Modelos Moleculares , Mutagênese/genética , N-Metilaspartato/farmacologia , Técnicas de Patch-Clamp , Polimicrogiria/diagnóstico por imagem , Ratos , Transfecção
12.
Epilepsy Behav ; 98(Pt B): 322-327, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30598258

RESUMO

This paper will explore the nature of psychiatric co-morbidities in people with an intellectual disability (ID) who have epilepsy. The complexity of clinical presentations and associated co-morbidities require thorough assessment utilising both neurological and psychiatric skills. The neurologist plays a central role in the management of epilepsy in people with ID and therefore requires basic competencies in the assessment of neuropsychiatric co-morbidities. This is key to liaison with other specialist services to ensure individuals receive holistic person-centred care. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".


Assuntos
Epilepsia/psicologia , Transtornos Mentais/terapia , Neurologistas , Papel do Médico , Competência Clínica , Comorbidade , Epilepsia/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/psicologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , América do Norte/epidemiologia , Padrões de Prática Médica , Âmbito da Prática
13.
J Am Chem Soc ; 140(27): 8415-8419, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29936832

RESUMO

We report the total synthesis of the natural products isodihydrokoumine and (19 Z)-taberpsychine in 11 steps each and (4 R)-isodihydrokoumine N4-oxide in 12 steps from commercially available starting materials. The key reactions include an intramolecular [3 + 2] nitrone cycloaddition and Lewis acid mediated cyclizations of a common intermediate to provide the core structures of either taberpsychine or isodihydrokoumine.

14.
Br J Psychiatry ; 212(4): 215-221, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29506597

RESUMO

BACKGROUND: Mental disorders in children and adolescents have an impact on educational attainment. Aims To examine the temporal association between attainment in education and subsequent diagnosis of depression or self-harm in the teenage years. METHOD: General practitioner, hospital and education records of young people in Wales between 1999 and 2014 were linked and analysed using Cox regression. RESULTS: Linked records were available for 652 903 young people and of these 33 498 (5.1%) developed depression and 15 946 (2.4%) self-harmed after the age of 12 but before the age of 20. Young people who developed depression over the study period were more likely to have achieved key stage 1 (age 7 years) but not key stage 2 (age 11) (hazard ratio (HR) = 0.79, 95% CI 0.74-0.84) milestones, indicating that they were declining in academic attainment during primary school. Conversely, those who self-harmed were achieving as well as those who did not self-harm in primary school, but showed a severe decline in their attainment during secondary school (HR = 0.72, 95% CI 0.68-0.78). CONCLUSIONS: Long-term declining educational attainment in primary and secondary school was associated with development of depression in the teenage years. Self-harm was associated with declining educational attainment during secondary school only. Incorporating information on academic decline with other known risk factors for depression/self-harm (for example stressful life events, parental mental health problems) may improve risk profiling methods. Declaration of interest None.


Assuntos
Desempenho Acadêmico/estatística & dados numéricos , Transtorno Depressivo/epidemiologia , Instituições Acadêmicas/estatística & dados numéricos , Comportamento Autodestrutivo/epidemiologia , Adolescente , Criança , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Armazenamento e Recuperação da Informação , Masculino , Modelos de Riscos Proporcionais , País de Gales/epidemiologia
15.
Epilepsia ; 59(10): 1867-1880, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30178479

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Gerenciamento Clínico , Epilepsia , Anticonvulsivantes/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/terapia , Humanos
16.
J Org Chem ; 83(11): 6235-6242, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29757647

RESUMO

The treatment of donor-acceptor cyclopropanes with the a strong hydrogen bond donor, HFIP, activated the cyclopropanes (via presumed hydrogen bonding) toward homo-Michael additions with indoles as the nucleophiles. This reaction proceeded without the need for high pressure or catalysis.

17.
BMC Med Genet ; 17(1): 34, 2016 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-27113213

RESUMO

BACKGROUND: Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. METHODS: We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. RESULTS: 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. CONCLUSIONS: We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults.


Assuntos
Variações do Número de Cópias de DNA , Epilepsia/genética , Deficiência Intelectual/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Deleção de Sequência , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , País de Gales , Adulto Jovem
18.
Epilepsia ; 57(11): 1870-1878, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27634349

RESUMO

OBJECTIVE: To quantify the experience of discrimination, domestic violence, abuse, and other stressful life events in people with epilepsy in comparison with the general population and people with other chronic conditions. To assess whether any excess relative burden of these adversities could explain the higher rates of depression in people with epilepsy. METHODS: The Adult Psychiatric Morbidity Survey 2007 used comprehensive interviews with 7,403 individuals living in private residences in England. Doctor-diagnosed epilepsy and other chronic conditions were established by self-report. Discrimination, domestic violence, physical and sexual abuse, and other stressful life events were assessed using computerized self-completion and a face-to-face interview, respectively. RESULTS: People with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems (adjusted odds ratio [OR] 7.1; 95% confidence interval [CI] 3.1-16.3), than the general population without epilepsy. This estimate was substantially greater in people with epilepsy than for people with other chronic conditions. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events. In exploratory analyses, assuming they lie on the causal pathway, discrimination, domestic violence, and sexual abuse explained 42.7% of the total effect of the relationship between epilepsy and depression or anxiety disorders. SIGNIFICANCE: People with epilepsy can face a range of psychosocial adversities and extensively report feeling discriminated against as compared to the general population. In addition, if confirmed in longitudinal studies, the results suggest that these psychosocial adversities may have a significant role in the development of psychiatric comorbidity and may be targets for future interventions.


Assuntos
Discriminação Psicológica/fisiologia , Violência Doméstica , Epilepsia/complicações , Epilepsia/psicologia , Estresse Psicológico/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Planejamento em Saúde Comunitária , Comorbidade , Inglaterra/epidemiologia , Epilepsia/epidemiologia , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Delitos Sexuais , Adulto Jovem
20.
Org Biomol Chem ; 13(3): 655-71, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25425071

RESUMO

This review summarizes research directed towards the formation of carbocyclic adducts from donor-acceptor cyclopropanes. The focus of the review is on annulation and cycloaddition reactions (both inter- and intramolecularly) mediated by Lewis or protic acid, bases, or thermal conditions. Rearrangements resulting in carbocycles and those reactions mediated by transition metal catalysis have been excluded.

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