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The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.

Background: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. Methods: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 Findings: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 patientsvs1 [vssix [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patientsvs12 [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). Interpretation: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.

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients 60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials., Ross Russell et al. report novel details of COVID-19 neurological complications: multiple overlapping diagnoses in the same patients, a severe encephalopathy atypical for delirium, and a lowered threshold for stroke in younger adults. Higher age, pre-morbid frailty score and white cell count predicted clinical outcome., Graphical Abstract Graphical Abstract

Background:Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.Methods:During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.Findings:The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation:To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding: None.

Reply by the current author to the comments made by Mark A Oldham et al (see record 2020-79526-008) and Dorothy Wade et al (see record 2020-79526-009) on the original article (see record 2020-71085-023) We thank Dorothy Wade and colleagues and Mark Oldham and colleagues for their recognition of the cross-speciality effort of members of the UK's major professional neuroscience bodies who undertook this challenging UK-wide study during the exponential phase of the COVID-19 pandemic We also welcome the involvement of geriatricians and psychologists in future research We agree that delirium is common, especially in severe infections and in the intensive care unit As stated in our Article, we acknowledge that the study might have not recorded all such cases Changes in mental status with clear and recognised risk factors were not the focus of this study We agree that if such commonly observed complications were included, they might have substantially increased the number of patients recruited, mirroring the situation in other critical illnesses In this situation, the burden of CNS complications arising from COVID-19 would be even greater than we found in our study (PsycInfo Database Record (c) 2020 APA, all rights reserved)

COVID-19 outbreak which originated from Wuhan, a city in China has spread to over 180 countries in the world, disrupting several sectors of the human life, and causing deaths. This unprecedented event has affected 55 countries in Africa in different ways. This study aims to outline the current epidemiological data of COVID-19 in Africa. The number of confirmed cases and deaths in Africa was obtained from COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Mortality rate and daily cumulative index were calculated for each country. The mortality rate in Africa is low compared to other Continents regardless of the high Daily Cumulative Index recorded.

Background: Increasingly neurological complications of COVID-19 are identified, mostly in small series. Larger studies have been limited by both geography and specialty.Consequently, the breadth of complications is not represented. Comprehensive characterization of clinical syndromes is critical to rationally select and evaluate potential therapies.Methods: During the exponential pandemic phase, we developed coordinated online portals for rapid notification across the spectrum of major UK neuroscience bodies, representing neurology, stroke, psychiatry, and intensive care. Evidence of infection and clinical case definitions were applied prospectively. Cases were compared to overall Government Public Health COVID-19 reporting.Findings: Within three weeks, 153 cases were notified, both geographically and temporally representative of overall COVID-19 Public Health reports. Median (range) age was 71 (23-94) years. 77 (62%) had a cerebrovascular event: 57 (74%) ischemic strokes, nine (12%) intracerebral hemorrhages, and one CNS vasculitis.The second most common group were 39 (31%) who had altered mental status, including 16 (41%) with encephalopathy of whom seven (44%) had encephalitis. The remaining 23 (59%) had a psychiatric diagnosis of whom 21 (92%) were new diagnoses; including ten (43%) with psychosis, six (26%) neurocognitive (dementia-like) syndrome, and 4 (17%) an affective disorder. Cerebrovascular events predominated in older patients. Conversely, altered mental status, whilst present in all ages, had disproportionate representation in the young.Interpretation: This is the first nationwide, cross-specialty surveillance study of acute complications of COVID-19 in the nervous system. Alteration in mental status was common, reflecting encephalopathy/encephalitis and primary psychiatric diagnoses, often in young patients.These data provide valuable and timely information urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy throughout the areas of neurology and neuropsychiatry.

Seizures are a common feature of many acquired and genetic syndromes and the predominant feature of some illnesses. We discuss the evidence for the genetic basis of epilepsy and the current knowledge of the genetic architecture of epilepsy. Genetic causes are varied, and so for an effective testing strategy, you must first understand the clinical scenario as clearly as possible; testing for progressive myoclonus epilepsy is different from severe myoclonic epilepsy of infancy. A variety of structural genomic, de novo dominant, repeat expansion, and mitochondrial mutations can cause epilepsy, and these are discussed in detail. Working in a multidisciplinary team for planning testing and interpreting results is increasingly important for returning clinically significant results.

Our genetic code is satisfyingly reliable. It does not suffer circadian fluctuations—there is no need for an ‘early morning’ or ‘fasting’ DNA test. It does not transmute over time—there is no need to resample or to compare results with an aged-matched sample. It does not suffer the vagaries of the test–retest variation as with an erythrocyte sedimentation rate or serum creatine kinase. The famous twisted-ladder of the double helix structure provides great physical and chemical stability. This inherent steadfastness is the tenet on which Michael Crichton’s Jurassic Park is based, as well as countless real and fictionalised court-room dramas. These features may predicate the optics through which we view a genetic disorder: indelible, inevitable, fixed and inert. In reality, no branch of medicine is as straightforward as we were initially taught—and medical genetics is unrecognisable from the undergraduate lectures of only a couple of decades ago. Somatic variation, mosaicism and heteroplasmy are but some of the mechanisms that undermine the superficial but false impression of genetic constancy. Consider the gamut of genetic disorders that break from this archetype, such as the paroxysmal conditions. There are the familial hemiplegic migraine disorders ( CACNA1A, ATP1A2, SCN1A, PRRT2 ) that produce spells on a spectrum …

Introduction The importance of parental mental health as a determinant of infant and child outcomes is increasingly acknowledged. Yet, there is limited information regarding paternal mental health during the perinatal period. The aim of this review is to summarize existing clinical research regarding paternal mental health in the perinatal period in various contexts, and its possible impact on infant development. Method An electronic literature search was conducted using MEDLINE and PubMed databases. Key texts were used to cross-check for any further articles of interest. Results Men are at increased risk of mental health problems during the transition to fatherhood, as well as during the perinatal period. Paternal mental health during the perinatal period has been shown to impact on their child's emotional and behavioral development. However, research addressing the needs of fathers with mental illness and the impact of their illness on their infant and family has been limited. Conclusions A paradigm shift is required, from a focus on women following childbirth and women with pre-existing psychiatric disorders, to a broader family perspective with the focus firmly on parent–infant relationships. This paradigm shift needs to involve greater research into the fathering role and paternal mental illness during the perinatal period, including further studies into risk factors, impact on the family system, and the most appropriate form of intervention and service provision.

The aim of this study was to compare the relative benefits and acceptability of two different group-based mindfulness psychotherapy interventions among women with breast and gynecologic cancer. Data from 42 women who completed an 8-week mindfulness-based cognitive therapy (MBCT) program comprising 22 contact hours were compared to data from 24 women who completed a 6-week mindfulness meditation program (MMP) comprising 9 contact hours. Distress, quality of life (QOL), and mindfulness were evaluated pre- (T1) and post-intervention (T2). ANCOVA was used to analyse the relationship between intervention type and T1 score on outcome variable change scores. Participants’ perceptions of benefit and acceptability were assessed. The participants did not differ on clinical or demographic variables other than MBCT participants were more likely than MMP participants to have a past history of anxiety or depression (p = .01). Scores on distress, QOL, and mindfulness improved from T1 to T2 with medium to large effect sizes for the MMP (p = .002, d = .07; p = .001, d = .08; p = .005, d = .06, respectively) and MBCT (p

This study aims to examine the acceptability and effectiveness of an antenatal group intervention designed to reduce the severity of depression and anxiety symptoms and improve maternal attachment in pregnant women with current or emerging depression and anxiety. Women who participated in the program completed pre- and posttreatment measures of depression (Centre of Epidemiological Studies Depression Scale) and Edinburgh Postnatal Depression Scale), anxiety (State-Trait Anxiety Inventory) and maternal attachment (Condon Maternal Antenatal Attachment Scale). Participants also completed a satisfaction questionnaire and provided general feedback about the group intervention and experience. A total of 48 women (M = 26 weeks of gestation) commenced and 37 (77 %) completed at least 80 % of the six session group intervention. Significant improvements with moderate to large effect sizes were observed for depression as measured on the Centre of Epidemiological Studies Depression Scale (CES-D) (p

Diagnosis and treatment of cancer are associated with substantial challenges to quality of life (QOL) and high rates of psychological distress. As survival rates improve and more cancer patients are living longer, identifying effective, cost-efficient psychosocial interventions to alleviate disease burden is increasingly important. We evaluated a mindfulness-based cognitive therapy (MBCT) program modified for oncology settings among women with breast and gynecologic cancer. Consistent with our hypotheses, significant improvements in distress, QOL, mindfulness and posttraumatic growth were observed after completion of the program and these gains were maintained 3 months later. Participants perceived the group program to be acceptable and beneficial. Inclusion of the formal MBCT program in routine clinical care in our setting, however, proved too expensive, prompting the evaluation of an alternative, abbreviated group-focused mindfulness meditation program (MMP). Comparison of outcomes between the formal MBCT program and the less resource-intensive MMP provide preliminary evidence of equivalence in improvements observed in distress, QOL and mindfulness, in the short term. Overall, these findings add to the limited existing data on MBCT in oncology settings and demonstrate the potential benefits of meditation in a heterogeneous group of women with cancer.

In Saccharomyces cerevisiae, glycosylphosphatidylinositol (GPI)-anchored cell wall mannoproteins, including alpha-agglutinin, are secreted to the cell surface through vesicular transport pathways. At the cell surface the GPI anchors are cleaved within the glycan, then transglycosylated to form a covalent cross-link to 1,6-beta-glucan. Among mutants that were temperature-sensitive for growth and for ability to cross-link the mannoprotein alpha-agglutinin to the cell wall, one strain was complemented by BET1, which encodes an ER-Golgi v-SNARE. Temperature-sensitive mutations in BET1 caused aberrations in cell wall structure, including excretion of alpha-agglutinin into the medium, sensitivity to lysis with Zymolyase and hypersensitivity to Calcofluor White. At restrictive temperatures, bet1 mutations block secretion of invertase and other proteins, but alpha-agglutinin was excreted into the extracellular medium. In wild-type parental or bet1 cells, secretion of alpha-agglutinin also continued after protein synthesis was blocked with cycloheximide. This secretion was due to continued export of a significant amount of alpha-agglutinin from compartments distal to the BET1-dependent secretion step. Thus, in bet1 cells the ER-Golgi block allowed secretion to continue, but prevented cell wall incorporation of the alpha-agglutinin. Therefore, a mutation early in the secretion pathway caused aberrant cell wall synthesis by preventing localization of key components required in wall cross-links.

The importance of parental mental health as a determinant of infant and child outcomes is increasingly acknowledged. Yet, there is limited information regarding paternal mental health during the perinatal period. The aim of this review is to summarize existing clinical research regarding paternal mental health in the perinatal period in various contexts, and its possible impact on infant development.An electronic literature search was conducted using MEDLINE and PubMed databases. Key texts were used to cross-check for any further articles of interest.Men are at increased risk of mental health problems during the transition to fatherhood, as well as during the perinatal period. Paternal mental health during the perinatal period has been shown to impact on their child's emotional and behavioral development. However, research addressing the needs of fathers with mental illness and the impact of their illness on their infant and family has been limited.A paradigm shift is required, from a focus on women following childbirth and women with pre-existing psychiatric disorders, to a broader family perspective with the focus firmly on parent-infant relationships. This paradigm shift needs to involve greater research into the fathering role and paternal mental illness during the perinatal period, including further studies into risk factors, impact on the family system, and the most appropriate form of intervention and service provision.

Reluctantly, I must thank Roberts for bringing to greater attention Lam's miraculous hiccough cure (plugging both ears tightly, pushing both right and left tragus, and drinking the entire glass of water through the straw without pause, without releasing the pressure over the ears).1 It certainly works. Crushingly, I was under the misapprehension that the cure was mine alone. I thought that the first professorship of …