Aim
To evaluate improvement in knowledge and clinical behaviour among healthcare professionals after attendance at paediatric epilepsy training (PET) courses.
Method
Since 2005, 1‐day PET courses ...have taught evidence‐based paediatric epilepsy management to doctors and nurses in low‐, middle‐, and high‐income countries. A cohort study was performed of 7528 participants attending 252 1‐day PET courses between 2005 and 2020 in 17 low‐, middle‐, and high‐income countries, and which gathered data from participants immediately after the course and then 6 months later. Training outcomes were measured prospectively in three domains (reaction, learning, and behaviour) using a mixed‐methods approach involving a feedback questionnaire, a knowledge quiz before and after the course, and a 6‐month survey.
Results
Ninety‐eight per cent (7217 of 7395) of participants rated the course as excellent or good. Participants demonstrated knowledge gain, answering a significantly higher proportion of questions correctly after the course compared to before the course (88% 47 883 of 54 196, correct answers/all quiz answers, vs 75% 40 424 of 54 196; p < 0.001). Most survey responders reported that the course had improved their epilepsy diagnosis and management (73% 311 of 425), clinical service (68% 290 of 427), and local epilepsy training (68% 290 of 427).
Interpretation
This was the largest evaluation of a global epilepsy training course. Participants reported high course satisfaction, showed knowledge gain, and described improvements in clinical behaviour 6 months later. PET supports the global reduction in the epilepsy ‘treatment gap’ as promoted by the World Health Organization.
Short course training, particularly in low‐income settings, is rarely carefully evaluated. This study reports the findings, using a well‐established evaluation framework, of 250 1‐day paediatric epilepsy training courses delivered in 17 countries over 15 years. Participants conveyed high course satisfaction, demonstrated a significant improvement in knowledge after the course, and reported positive changes in clinical practice 6 months later.
This original article is commented by Wiebe on pages 967–968 of this issue.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
How does the form of the Bildungsroman reflect the drive to decolonisation? If the world or postcolonial Bildungsroman is concerned with figuring the development of human personality (as Joseph ...Slaughter has argued), it is at one and the same time concerned with the allegorisation of national development. Yet, the political exigencies that urge on the writing of decolonisation can equally be served by realism. Perhaps the paradigmatic postcolonial Bildungsroman, Tsitsi Dangarembga's Nervous Conditions is also notable for the tension it presents between realism and allegory. This article makes an intervention in the politics of such formalist debates within the Bildungsroman as the tension between allegory and realism or the temporality of its narration in order to gauge their relation to decolonisation. In so doing, it examines Dangarembga's Tambudzai trilogy-including the two sequels The Book of Not and This Mournable Body-and its intertexts, such as the work of Frantz Fanon.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
During 2015-16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other ...neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil.
We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses.
Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions.
Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most paleoclimate studies of Mainland Southeast Asia hydroclimate focus on the summer monsoon, with few studies investigating rainfall in other seasons. Here, we present a multiproxy stalagmite ...record (45,000 to 4,000 years) from central Vietnam, a region that receives most of its annual rainfall in autumn (September-November). We find evidence of a prolonged dry period spanning the last glacial maximum that is punctuated by an abrupt shift to wetter conditions during the deglaciation at ~14 ka. Paired with climate model simulations, we show that sea-level change drives autumn monsoon rainfall variability on glacial-orbital timescales. Consistent with the dry signal in the stalagmite record, climate model simulations reveal that lower glacial sea level exposes land in the Gulf of Tonkin and along the South China Shelf, reducing convection and moisture delivery to central Vietnam. When sea level rises and these landmasses flood at ~14 ka, moisture delivery to central Vietnam increases, causing an abrupt shift from dry to wet conditions. On millennial timescales, we find signatures of well-known Heinrich Stadials (HS) (dry conditions) and Dansgaard-Oeschger Events (wet conditions). Model simulations show that during the dry HS, changes in sea surface temperature related to meltwater forcing cause the formation of an anomalous anticyclone in the Western Pacific, which advects dry air across central Vietnam, decreasing autumn rainfall. Notably, sea level modulates the magnitude of millennial-scale dry and wet phases by muting dry events and enhancing wet events during periods of low sea level, highlighting the importance of this mechanism to autumn monsoon variability.
An examination of five temperature and five precipitation extreme indicators reveals an increase in both temperature and precipitation extremes over the 1926–2000 period in the northeast United ...States, with most of this increase occurring over the past four decades. Empirical orthogonal function (EOF) analysis of winter frost days (FD) and warm nights (TN90) and also winter consecutive dry days (CDD) and very wet days (R95T) over the 1950–2000 period reveals that some of the variability associated with changes in these extremes may be explained by variations in the Arctic Oscillation (AO), El Niño–Southern Oscillation (ENSO), and Pacific–North American (PNA) pattern. The most prominent feature of these results was the high correlation between the leading EOF of frost days and warm nights and the AO. Winter composites of temperature and precipitation extreme indicators were examined for different phases of the AO and ENSO during the 1926–2000 period. Overall, the AO is a better predictor of winter warm nights, while the ENSO is a better predictor of consecutive dry days in the northeast United States.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The British Antibiotic and Silver Impregnated Catheter Shunt (BASICS) trial established level I evidence of the superiority of antibiotic-impregnated catheters in the prevention of infection of newly ...implanted ventriculoperitoneal shunts (VPSs). A wealth of patient, shunt, and surgery-specific data were collected from trial participants beyond that of the prespecified trial objectives.
This post hoc analysis of the BASICS survival data explores the impact of patient age, hydrocephalus etiology, catheter type, valve type, and previous external ventricular drain on the risk of infection or mechanical failure. Time to failure was analyzed using Fine and Gray survival regression models for competing risk.
Among 1594 participants, 75 patients underwent revision for infection and 323 for mechanical failure. Multivariable analysis demonstrated an increased risk of shunt infection associated with patient ages < 1 month (subdistribution hazard ratio sHR 4.48, 95% CI 2.06-9.72; p < 0.001) and 1 month to < 1 year (sHR 2.67, 95% CI 1.27-5.59; p = 0.009), as well as for adults with posthemorrhagic hydrocephalus (sHR 2.75, 95% CI 1.21-6.26; p = 0.016). Age ≥ 65 years was found to be independently associated with reduced infection risk (sHR 0.26, 95% CI 0.10-0.69; p = 0.007). Antibiotic-impregnated catheter use was also associated with reduced infection risk (sHR 0.43, 95% CI 0.22-0.84; p = 0.014). Independent risk factors predisposing to mechanical failure were age < 1 month (sHR 1.51, 95% CI 1.03-2.21; p = 0.032) and 1 month to < 1 year (sHR 1.31, 95% CI 0.95-1.81; p = 0.046). Age ≥ 65 years was demonstrated to be the only independent protective factor against mechanical failure risk (sHR 0.64, 95% CI 0.40-0.94; p = 0.024).
Age is the predominant risk for VPS revision for infection and/or mechanical failure, with neonates and infants being the most vulnerable.
Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological ...disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.
We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics.
Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34–60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 20% had Zika, 55 27% had chikungunya, and two 1% had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 23% patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 47% of 55 patients with chikungunya infection vs six 15% of 41 with Zika infection; p=0·0008), especially myelitis (12 22% patients). Zika infection was more often associated with PNS disease (26 63% of 41 patients with Zika infection vs nine 16% of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 61% patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days IQR 20–30 vs 17 days 10–20; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047).
There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation.
Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research.
For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect the epigenetic regulatory machinery and signaling molecules, leading to a block in hematopoietic differentiation. ...Constitutive signaling from mutated growth factor receptors is a major driver of leukemic growth, but how aberrant signaling affects the epigenome in AML is less understood. Furthermore, AML cells undergo extensive clonal evolution, and the mutations in signaling genes are often secondary events. To elucidate how chronic growth factor signaling alters the transcriptional network in AML, we performed a system-wide multi-omics study of primary cells from patients suffering from AML with internal tandem duplications in the FLT3 transmembrane domain (FLT3-ITD). This strategy revealed cooperation between the MAP kinase (MAPK) inducible transcription factor AP-1 and RUNX1 as a major driver of a common, FLT3-ITD-specific gene expression and chromatin signature, demonstrating a major impact of MAPK signaling pathways in shaping the epigenome of FLT3-ITD AML.
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•FLT3-ITD signaling is associated with a common gene expression signature•FLT3-ITD-specific gene expression is associated with a common chromatin signature•FLT3-ITD AML displays chronic activation of the inducible transcription factor AP-1•AP-1 cooperates with RUNX1 to shape the epigenome of FLT3-ITD AML
Cauchy et al. identify a specific gene expression and regulatory signature associated with aberrant signaling in acute myeloid leukemia with FLT3-ITD mutations. In FLT3-ITD AML, the inducible transcription factor AP-1 is chronically activated and cooperates with RUNX1, shaping the epigenome to transactivate specific target genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Objectives Enteroviruses (EV) and human parechoviruses (HPeV) infections are increasingly identified in neonates and young children with sepsis, meningitis and encephalitis. We investigated ...EV and HPeV viral loads in plasma and cerebrospinal fluid (CSF) among those presenting with sepsis or central nervous system (CNS) disease to gain understanding of the nature of these infections. Methods Detections frequencies and viral loads of EV and HPeV RNA were compared in plasma and CSF obtained from infected children originally identified on sepsis or CNS screening. Results Two distinct infection profiles were identified; 11 subjects with CNS disease, showed higher or similar viral loads in CSF than in plasma (median plasma:CSF ratio 0.5), whereas 14 children with sepsis showed low or undetectable viral loads in CSF and high viral loads in plasma (mean ratio 5700). HPeV type 3 and one EV serotype (coxsackievirus B2) were primarily associated with the latter presentation. Conclusions Simple detection of EV or HPeV RNA in CSF is not predictive of CNS disease, especially in the absence of clinical markers ( i.e. pleocytosis). Screening of plasma can identify EV and HPeV RNA in a substantial proportion of sepsis cases, some of which will be missed if CSF samples alone are screened.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in ...hospitalised children and adolescents.
We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data.
Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9-5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1-17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 88%), peripheral nervous system involvement (n=10 40%), behavioural change (n=9 36%), and hallucinations at presentation (n=6 24%). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 48% of 27 patients vs 1 <1% of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 80% of 25 patients vs six 22% of 27 patients, p=0·0001) and received immunomodulatory treatment (22 88% patients vs 12 44% patients, p=0·045). 17 (33%) patients (10 37% in the COVID-19 neurology group and 7 28% in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group).
This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes.
UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research.
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