Genomic epidemiology and evolution of rhinovirus in western Washington State, 2021-22.

BACKGROUND: Human rhinoviruses (RV) primarily cause the common cold, but infection outcomes vary from subclinical to severe cases, including asthma exacerbations and fatal pneumonia in immunocompromised individuals. To date, therapeutic strategies have been hindered by the high diversity of serotypes. Global surveillance efforts have traditionally focused on sequencing VP1 or VP2/VP4 genetic regions, leaving gaps in our understanding of RV genomic diversity. METHODS: We sequenced 1,078 RV genomes from nasal swabs of symptomatic and asymptomatic individuals to explore viral evolution during two epidemiologically distinct periods in Washington State: when the COVID-19 pandemic affected the circulation of other seasonal respiratory viruses except for RV (February - July 2021), and when the seasonal viruses reemerged with the severe RSV and influenza outbreak (November-December 2022). We constructed maximum likelihood and BEAST-phylodynamic trees to characterize intra-genotype evolution. RESULTS: We detected 99 of 168 known genotypes and observed inter-genotypic recombination and genotype cluster swapping from 2021 to 2022. We found a significant association between the presence of symptoms and viral load, but not with RV species or genotype. Phylodynamic trees, polyprotein selection pressure, and Shannon entropy revealed co-circulation of divergent clades within genotypes with high amino acid constraints throughout polyprotein. DISCUSSION: Our study underscores the dynamic nature of RV genomic epidemiology within a localized geographic region, as more than 20% of existing genotypes within each RV species co-circulated each studied month. Our findings also emphasize the importance of investigating correlations between rhinovirus genotypes and serotypes to understand long-term immunity and cross-protection.

Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Epilepsy professionals' views on sudden unexpected death in epilepsy counselling: A tale of two countries.

BACKGROUND AND PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy mortality. All international guidance strongly advocates for clinicians working with people with epilepsy (PWE) to discuss SUDEP. Clinician views working with PWE in the UK and Norway on SUDEP counselling are compared. METHODS: A cross-sectional online mixed methodology survey of 17 Likert and free-text response questions using validated themes was circulated via International League against Epilepsy/Epilepsy Specialist Nurses Association in the UK and International League against Epilepsy/Epilepsinet in Norway using a non-discriminatory exponential snowballing technique leading to non-probability sampling. Quantitative data were analysed using descriptive statistics and Mann-Whitney, Kruskal-Wallis, chi-squared and Fisher's exact tests. Significance was accepted at p < 0.05. Thematic analysis was conducted on free-text responses. RESULTS: Of 309 (UK 197, Norway 112) responses, UK clinicians were more likely to have experienced an SUDEP (p < 0.001), put greater importance on SUDEP communication (p < 0.001), discuss SUDEP with all PWE particularly new patients (p < 0.001), have access and refer to bereavement support (p < 0.001) and were less likely to never discuss SUDEP (p < 0.001). Significant differences existed between both countries' neurologists and nurses in SUDEP counselling with UK clinicians generally being more supportive. UK responders were more likely to be able to identify bereavement support (p < 0.001). Thematic analysis highlighted four shared themes and two specific to Norwegians. DISCUSSION: Despite all international guidelines stating the need/importance to discuss SUDEP with all PWE there remain hesitation, avoidance and subjectivity in clinicians having SUDEP-related conversations, more so in Norway than the UK. Training and education are required to improve communication, engagement and decision making.

Identifying co-morbidities and risk in people with epilepsy: The Maltese experience.

BACKGROUND: People with epilepsy are at increased risk of multiple co-morbidities that may influence risk of adverse outcomes including impact on quality of life and premature mortality. These risk factors include potentially modifiable clinical characteristics associated with sudden unexpected death in epilepsy (SUDEP). For services to tackle risk, the clinical complexity of the target epilepsy population needs to be defined. While this has been comprehensively studied in large, economically developed countries little knowledge of these issues exist in small economically developed countries, like Malta (population: 500,000). METHODS: This was a single centre study focused exclusively on patients attending Gozo General Hospital (GGH) Malta. STROBE guidance for reporting cross sectional studies was used to design and report the study. This was a retrospective review of standard care and SUDEP and seizure risks provided to all adults (over 18 years) with epilepsy attending GGH (2018-2021). RESULTS: The review identified 68 people and 92% were compliant with their anti-seizure medication. A fifth (21%) had an intellectual disability. Despite only one patient having a psychotic illness, 19% were on antipsychotic medication. Only 18% of patients had a specific epilepsy care plan, 6% nocturnal surveillance and none had received advice on SUDEP. DISCUSSION: Patient outcomes may be improved with increasing rates of personalized epilepsy care plans, appropriate nocturnal surveillance and reducing the prescription of antipsychotic medication as it is associated with greater risk of mortality. Issues such as stigma and shame appear to play a significant role in small communities and their access to care.

Efficacy and tolerability of Brivaracetam in people with intellectual disability compared to those without intellectual disability.

INTRODUCTION: In England, nearly a quarter of people with intellectual disability (PwID) have epilepsy. Though 70 % of PwID have pharmaco-resistant seizures only 10 % are prescribed anti-seizure medication (ASMs) licenced for pharmaco-resistance. Brivaracetam (BRV) licenced in 2016 has had nine post-marketing studies involving PwID. These studies are limited either by lack of controls or not looking at outcomes based on differing levels of ID severity. This study looks at evidence comparing effectiveness and side-effects in PwID to those without ID prescribed Brivaracetam (BRV). METHODS: Pooled case note data for patients prescribed BRV (2016-2022) at 12 UK NHS Trusts were analysed. Demographics, starting and maximum dose, side-effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 37 PwID (mild 17 M/P 20) were compared to 102 without ID. Mean start and maximum dose was lower for PwID than non-ID. Mean maximum dose reduced slightly with ID severity. No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in BRV's efficacy i.e. >50 % seizure reduction or tolerability. Mental and behavioural side-effects were more prevalent for PwID (27.0 % ID, 17.6 % no ID) but not significantly higher (P = 0.441) or associated with ID severity (p = 0.255). CONCLUSION: This is the first study on BRV, which compares ID cohorts with differing severity and non-ID. Efficacy, tolerability and side-effects reported are similar across differing ID severity to those with no ID.

People with Intellectual Disabilities, Dysphagia and Post-Covid Syndrome.

People with Intellectual Disability (ID) were more likely to contract COVID-19 infection and more likely to die from the consequences. However, there is no evidence on the long-term impact of COVID-19 infection in people with ID. Post-Covid Syndrome (PCS) is an established diagnosis that requires specialist clinical support. To date there is no data on how common PCS is in people with ID, or how symptoms present. Dysphagia is identified as a clinical marker because of the known association with PCS, and the clear objective diagnostic criteria applicable through specialist assessment. This investigation presents a cohort of people with ID, who developed dysphagia/worsening of dysphagia post diagnosis with COVID-19. Cases were identified through support from the Royal College of Speech and Language Therapists. Data was collected by electronic survey, including application of the COVID-19 Yorkshire Rehabilitation Scale-modified (C19-YRSm). The C19-YRSm is a validated assessment tool for PCS and it's impact upon functional disability. This case series identifies that symptoms consistent with PCS are present in people with ID, post-COVID-19 infection. The risk of diagnostic overshadowing or misdiagnosis is high due to the subjective nature and the quality of PCS symptoms. People with ID who develop PCS may not be readily identified by clinical services and therefore not be accessing the specialist medical support required. Furthermore, changes in behaviour secondary to PCS may lead to unnecessary increased prescribing of psychotropic medication which in itself risks worsening dysphagia. Dysphagia could be an important bellwether to identify PCS in people with ID.

Mood disorders in adults with epilepsy: a review of unrecognized facts and common misconceptions.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

Antiseizure medications prescribing for behavioural and psychiatric concerns in adults with an intellectual disability living in England.

Antiseizure medications (ASMs) are the second most widely prescribed psychotropic for people with intellectual disabilities in England. Multiple psychotropic prescribing is prevalent in almost half of people with intellectual disabilities on ASMs. This analysis identifies limited evidence of ASM benefit in challenging behaviour management and suggests improvements needed to inform clinical practice.

Post-COVID syndrome and adults with intellectual disability: another vulnerable population forgotten?

An area of interest presently is the lingering symptoms after COVID-19, i.e. post-COVID-19 syndrome (PCS). Specifics of diagnosis and management of PCS are emerging. However, vulnerable populations such as those with intellectual disabilities, who were disproportionately affected by the pandemic, risk being 'left behind' from these considerations.

The potential unintended consequences of Mental Health Act reforms in England and Wales on people with intellectual disability and/or autism.

The draft Mental Health Bill, which amends the Mental Health Act 1983 for England and Wales, proposes protections for people with intellectual disability and/or autism (ID/A) to prevent detention in hospital in the absence of mental illness. This editorial critically appraises the positive impact and unintended consequences of the proposed reforms for people with ID/A.

Patterns of antiseizure medications prescribing in people with intellectual disability and epilepsy: A narrative review and analysis.

People with intellectual disabilities (PwID) have a bidirectional relationship with epilepsy. Nearly 25% of PwID have seizures and 30% people with epilepsy are thought to have a significant intellectual impairment. Furthermore, 70% of PwID are thought to have treatment-resistant epilepsy. In the United Kingdom, antiseizure medications (ASMs) are the second most widely prescribed psychotropic agent for PwID. However, it is unclear what the current evidence and patterns is on current prescribing of ASMs, including when and how a case is made to withdraw them. A narrative review along with an analysis of large-scale NHS Digital published data (2015-2020) on several aspects of ASM prescribing by general practices for PwID was undertaken. The review results and data analysis are consolidated and presented as 11 themes to provide a comprehensive overview of the study topic. Recent studies estimate that one-third and one-fifth of PwID are prescribed ASMs. A history of epilepsy is seen as the primary prescribing reason; however, often it is a legacy, and the indication is no longer clear. The proportion receiving ASMs continues to rise with age. This pattern of use does not correlate well with seizure onset. There are limited data on de-prescribing ASMs in PwID. The study population heterogenicity, associated polypharmacy, multimorbidity and higher sudden unexpected death in epilepsy risks are outlined. Suggestions are made from available evidence for improving prescribing practices for PwID and seizures, and key areas for further research in this complex clinical area are outlined.

The UK psychiatrists' experience of rationalising antipsychotics in adults with intellectual disabilities: A qualitative data analysis of free-text questionnaire responses.

BACKGROUND: Overprescribing of off-licence psychotropic medications, particularly antipsychotics, for challenging behaviours in people with intellectual disabilities without a psychiatric disorder is a significant public health concern. In the United Kingdom, the National Health Service England launched an initiative in 2016, 'STopping Over-Medication of People with learning disabilities, autism or both (STOMP)', to address this concern. STOMP is supposed to encourage psychiatrists in the United Kingdom and elsewhere to rationalise psychotropic medication use in people with intellectual disabilities. The current study aims to gather UK psychiatrists' views and experience of implementing the STOMP initiative. METHODS: An online questionnaire was sent to all UK psychiatrists working in the field of intellectual disabilities (estimated 225). Two open-ended questions allowed participants to write comments in response to these questions in the free text boxes. One question asked about the challenges psychiatrists faced locally to implement STOMP, and the other asked for examples of successes and positive experiences from the process. The free text data were analysed using a qualitative method with the help of the NVivo 12 plus software. RESULTS: Eighty-eight (estimated 39%) psychiatrists returned the completed questionnaire. The qualitative analysis of free-text data has shown variation within services in the experience and views of the psychiatrists. In areas with good support for STOMP implementation provided through adequate resources, psychiatrists reported satisfaction in the process with successful antipsychotic rationalisation, better local multi-disciplinary and multi-agency working, and increased awareness of STOMP issues among the stakeholders such as people with intellectual disabilities and their caregivers and multidisciplinary teams, and improved quality of life caused by reduced medication-related adverse events in people with intellectual disabilities. However, where resource utilisation is not optimum, psychiatrists seemed dissatisfied with the process with little success in medication rationalisation. CONCLUSIONS: Whereas some psychiatrists are successful and enthusiastic about rationalising antipsychotics, others still face barriers and challenges. Much work is needed to achieve a uniformly positive outcome throughout the United Kingdom.

Survey of parents of children with intellectual disabilities and/or autism who experience chronic constipation.

BACKGROUND: Constipation is common in children with intellectual disabilities and/or autism, but poorly researched. This study looks to understand parental knowledge, attitudes and management practices towards constipation in children with intellectual disabilities and/or autism. METHODS: A cross-sectional online survey developed with patient facing organisations was circulated to parents of children with intellectual disabilities and/or autism using an exponential and non-discriminatory snowballing method for recruitment. A smaller sample were purposively sampled for their in-depth experiences. RESULTS: Of 68 responses, people were open to discussing constipation and knowledgeable about risk factors. In the qualitative interviews, of 15 parents, they wanted to be treated as an expert in their child's care. They desired a service that was more responsive when in difficulty. While wanting more information about medication options, parents want a more holistic approach. CONCLUSIONS: Services need more emphasis on holistic management. Listening to parents and treating them as experts is important.

Antidepressant prescribing for adult people with an intellectual disability living in England.

The prescribing of psychotropic medications for people with an intellectual disability has changed. In many locations across England, antidepressants have become the most widely prescribed psychotropic. In the context of the current NHS England STOMP programme to reduce inappropriate psychotropic prescribing for people with intellectual disability, there is an urgent need to understand whether this change reflects evidence-based use of the medications involved. There has been little analysis into the benefits or problems associated with the change and whether it is of concern. This paper offers a variety of possible explanations and opportunities to improve clinical practice and policy.

Impact of COVID-19 on mental health research: is this the breaking point?

There are many structural problems facing the UK at present, from a weakened National Health Service to deeply ingrained inequality. These challenges extend through society to clinical practice and have an impact on current mental health research, which was in a perilous state even before the coronavirus pandemic hit. In this editorial, a group of psychiatric researchers who currently sit on the Academic Faculty of the Royal College of Psychiatrists and represent the breadth of research in mental health from across the UK discuss the challenges faced in academic mental health research. They reflect on the need for additional investment in the specialty and ask whether this is a turning point for the future of mental health research.

Bone health, intellectual disability and epilepsy: An observational community-based study.

OBJECTIVES: Intellectual disability (ID) and epilepsy are independent risk factors for osteoporosis. Diverse predisposing factors influence this, for example in ID, genetics and poor nutrition and in epilepsy, anti-seizure medication (ASM). Around 25% people with ID have epilepsy, majority treatment resistant. ASMs polypharmacy is common. However, little is known about the bone-related characteristics of this vulnerable group. A prospective observational cohort study of bone profile across a community ID Epilepsy service was undertaken to understand this. MATERIALS & METHODS: Participants were on minimum 2 years of ASMs. Baseline demographics, epilepsy data, bone metabolism biomarkers, bone mineral density (BMD) and vitamin D levels were collected. Doses needed to correct vitamin D insufficiency/deficiency were calculated. RESULTS: At baseline, of 104 participants, 92 (90.2%) were vitamin D insufficient/deficient. Seventy-six (73.1%) had a DEXA scan, 50 of whom-in the osteopaenic/osteoporotic range. DEXA scores between ambulant and non-ambulant patients were significantly different (p = .05) but not for ID severity. A high alkaline phosphatase (ALP) predicted lower vitamin D levels. Borderline significance (p = .06) in calcium levels between normal and high ALP was identified. There were no significant associations between parathyroid hormone, inorganic phosphate and magnesium levels, with vitamin D status or DEXA hip T-scores. Normalizing vitamin D levels (mean 101.4 nmol/L) required an average of 1951IU cholecalciferol daily. CONCLUSIONS: Vitamin D deficiency is highly prevalent in people with ID and epilepsy treated with ASMs impacting likely on their bone health. Screening with vitamin D levels, ALP and DEXA in this group should be pro-actively and routinely considered.

Perceptions about mental healthcare for people with epilepsy in Africa.

BACKGROUND: Mental illness is commonly comorbid with epilepsy. In sub-Saharan Africa there exists limited access to neurological and psychiatric services predisposing to a "treatment gap" in epilepsy and mental healthcare. AIMS: To understand healthcare providers' knowledge, attitudes, and management practices toward epilepsy and comorbid mental illness in sub-Saharan Africa. METHODS: A cross-sectional online survey following the STROBE guidance was conducted among healthcare providers in sub-Saharan Africa. Eleven questions looking to ascertain clinician demographics, knowledge of epilepsy, and comorbid mental illness as well as management practices were developed. FINDINGS: Of 203 responses most (92%) respondents recognized a bi-directional relationship between mental health and epilepsy. However, mental illness screening in people newly diagnosed with epilepsy was infrequently performed (14%). Only 1 in 7 (16%) respondents had high confidence in their clinical competence at managing psychiatric comorbidities. Most would value further training (74%) and improvements to be made in current management practices within their local healthcare settings (94%). CONCLUSIONS: This pilot study highlights the need to improve the awareness of management of mental disorders in populations with epilepsy within sub-Saharan Africa in health providers there.

An 8-year study of admissions and discharges to a specialist intellectual disability inpatient unit.

BACKGROUND: In the United Kingdom, policy change has led to specialist intellectual disability inpatient bed reduction. Little evidence exists assessing the results for patients admitted to such units. This study evaluates the outcomes of a specialist intellectual disability inpatient unit. METHOD: Gender/age/ethnicity/intellectual disability severity/co-morbid psychiatric/developmental disorders, treatment length and stay data were collected. The health of the nation outcome scales for people with learning disabilities (HoNOS-LD) scores at admission, treatment completion and discharge were recorded. Analysis of these multiple variables and correlations within different patient groups was investigated using various statistical tests. RESULTS: Of 169/176 patients (2010-2018), admission to discharge, HoNOS-LD global and all individual items score decreased significantly, for all patient categories. Treatment completion to discharge duration was significant for the whole cohort. CONCLUSIONS: This is the largest study of intellectual disability inpatient outcomes. Discharge from the hospital appears not associated with duration of treatment. Using HoNOS-LD to demonstrate treatment effectiveness is recommended.

Psychiatry and neurodevelopmental disorders: experts by experience, clinical care and research.

People with neurodevelopmental disorders often present with challenging behaviours and psychiatric illnesses. Diagnosis and treatment require patients, families and healthcare professionals to work closely together in partnership, acknowledging their respective areas of expertise. Good treatment outcomes should also be underpinned by robust research evidence. Key research priorities are highlighted.

Oxygen for seizures, more questions than answers: A scoping review.

BACKGROUND: Ictal hypoxaemia is a feature seen in epileptic seizures, characterized by low oxygen saturations, increasing seizure prolongation risk and possibly contributing to sudden unexpected death in epilepsy (SUDEP). High flow oxygen is recommended in the management of seizures by UK's National Institute of Health and Care excellence (NICE); however, the evidence supporting this recommendation is unclear. AIMS: To identify the efficacy of oxygen in the seizure treatment. METHOD: A scoping review was conducted using PRISMA-ScR guidance. PsycINFO, EMBASE and MEDLINE were searched along with the references section of identified literature. Articles were critically appraised for study, patient, seizure, oxygen therapy and outcome characteristics, summarized and quality-assessed using Sackett's criteria. RESULTS: Literature search identified 623 articles of which five met the pre-criteria for full review. One animal study demonstrated favourable effects of oxygen administration. Three human studies also reported favourable effects of oxygen administration, while one reported outcomes that were not statistically significant. Study design concerns in all identified literature confounded the ability to assess efficacy. All five publications were assigned Sackett's score of 2b. CONCLUSION: There is a significant lack of evidence to support the efficacy of oxygen administration in epileptic seizures. Future research is needed.