Incidence and Types of Cardiac Arrhythmias in the Peri-Ictal Period in Patients Having a Generalized Convulsive Seizure.

BACKGROUND AND OBJECTIVES: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases. METHODS: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during inpatient video-EEG monitoring for epilepsy evaluation. Exclusion criteria were status epilepticus and an obscured video recording. We analyzed semiologic and cardiorespiratory features through video-EEG (VEEG), electrocardiogram, thoracoabdominal bands, and pulse oximetry. We investigated the presence of bradycardia, asystole, supraventricular tachyarrhythmias (SVTs), premature atrial beats, premature ventricular beats, nonsustained ventricular tachycardia (NSVT), atrial fibrillation (Afib), ventricular fibrillation (VF), atrioventricular block (AVB), exaggerated sinus arrhythmia (ESA), and exaggerated sinus arrhythmia with bradycardia (ESAWB). A board-certified cardiac electrophysiologist diagnosed and classified the arrhythmia types. Bradycardia, asystole, SVT, NSVT, Afib, VF, AVB, and ESAWB were classified as arrhythmias of interest because these were of SUDEP pathophysiology value. The main outcome was the occurrence of seizure-induced arrhythmias of interest during inpatient VEEG monitoring. Moreover, yearly follow-up was conducted to identify SUDEP cases. Binary logistic generalized estimating equations were used to determine clinical-demographic and peri-ictal variables that were predictive of the presence of seizure-induced arrhythmias of interest. The z-score test for 2 population proportions was used to test whether the proportion of seizures and patients with postconvulsive ESAWB or bradycardia differed between SUDEP cases and survivors. RESULTS: This study includes data from 249 patients (mean age 37.2 ± 23.5 years, 55% female) who had 455 seizures. The most common arrhythmia was ESA, with an incidence of 137 of 382 seizures (35.9%) (106/224 patients [47.3%]). There were 50 of 352 seizure-induced arrhythmias of interest (14.2%) in 41 of 204 patients (20.1%). ESAWB was the commonest in 22 of 394 seizures (5.6%) (18/225 patients [8%]), followed by SVT in 18 of 397 seizures (4.5%) (17/228 patients [7.5%]). During follow-up (48.36 ± 31.34 months), 8 SUDEPs occurred. Seizure-induced bradycardia (3.8% vs 12.5%, z = -16.66, p < 0.01) and ESAWB (6.6% vs 25%; z = -3.03, p < 0.01) were over-represented in patients who later died of SUDEP. There was no association between arrhythmias of interest and seizure severity biomarkers (p > 0.05). DISCUSSION: Markers of seizure severity are not related to seizure-induced arrhythmias of interest, suggesting that other factors such as occult cardiac abnormalities may be relevant for their occurrence. Seizure-induced ESAWB and bradycardia were more frequent in SUDEP cases, although this observation was based on a very limited number of SUDEP patients. Further case-control studies are needed to evaluate the yield of arrhythmias of interest along with respiratory changes as potential SUDEP biomarkers.

Quantitative cellular pathology of the amygdala in temporal lobe epilepsy and correlation with magnetic resonance imaging volumetry, tissue microstructure, and sudden unexpected death in epilepsy risk factors.

OBJECTIVE: Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction. METHODS: Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR-pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal-associated apnea. RESULTS: We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule-associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6-235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency. SIGNIFICANCE: Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.

Can Salmonella typhi Cause Acute Appendicitis?

Salmonella typhi, commonly known for causing typhoid fever, is recognized as a bacterium responsible for a wide range of gastrointestinal and systemic infections. While its systemic manifestations have been well-documented, its association with localized gastrointestinal complications, such as appendicitis, remains relatively rare and less explored. This case report presents a compelling clinical case of a 55-year-old patient who presented with symptoms of gastrointestinal distress and was diagnosed with S. typhi-induced appendicitis. The patient's history, clinical presentation, laboratory investigations, radiological findings, management, and outcomes are thoroughly discussed. The report also touches upon the broader context of appendicitis etiology and highlights the significance of prompt diagnosis and intervention in cases of Salmonella-induced appendicitis.

Process-evaluation of forest aerosol-cloud-climate feedback shows clear evidence from observations and large uncertainty in models.

Natural aerosol feedbacks are expected to become more important in the future, as anthropogenic aerosol emissions decrease due to air quality policy. One such feedback is initiated by the increase in biogenic volatile organic compound (BVOC) emissions with higher temperatures, leading to higher secondary organic aerosol (SOA) production and a cooling of the surface via impacts on cloud radiative properties. Motivated by the considerable spread in feedback strength in Earth System Models (ESMs), we here use two long-term observational datasets from boreal and tropical forests, together with satellite data, for a process-based evaluation of the BVOC-aerosol-cloud feedback in four ESMs. The model evaluation shows that the weakest modelled feedback estimates can likely be excluded, but highlights compensating errors making it difficult to draw conclusions of the strongest estimates. Overall, the method of evaluating along process chains shows promise in pin-pointing sources of uncertainty and constraining modelled aerosol feedbacks.

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3.

BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Fifty-year study of microplastics ingested by brachyuran and fish larvae in the central English North Sea.

Microplastics (MPs) are ubiquitous pollutants in marine environments. Among the many detrimental consequences of microplastic pollution, its consumption by marine biota is of particular relevance for human health, due to exposure through the food web. Long-term time-series biotic samples are overlooked sources of information for microplastics research. These collections are extremely valuable for the detection and monitoring of changes in marine environments. However, there are very few long-term studies (>10 years) of the uptake of microplastics by biota. Here, we used Dove Time Series planktonic samples (from 1971 to 2020) to assess the presence and prevalence of microplastics in the English North Sea coast over time. Fish and brachyuran larvae were selected due to their commercial importance and consequent implications for human health. A custom enzymatic digestion method was used to extract microplastics for FTIR-ATR polymer identification. An increasing cumulative trend in MP ingestion was identified. Cellophane and polyethylene terephthalate were the polymer types found most frequently in both taxa. Although a total higher microplastics uptake was observed in fish, consumption was not significantly different between taxa over time. Equally, results were not clearly related to microplastics shape or polymer type. This work did not find significant long-term evidence on the increasing uptake of microplastic particles by zooplankton over time. However, the results of this report identified additives, plasticisers, and other more complex and hazardous compounds that should not be released to the environment (e.g., bis-(2-hydroxyethyl) dimerate, propylene glycol ricinoleate) inside marine biota. The study detailed herein provides a case study for the use of long-term time-series in providing accurate assessments of microplastic pollution in marine biota.

Connecting Health and Social Services for Patients with Complex Care Needs: A Pan-Canadian Comparative Policy Research Program.

Comprehensive primary healthcare for patients with complex care needs requires connections to other health services, social services and community supports. This descriptive comparative policy research program used publicly available documents and informant interviews to examine progress toward integrated comprehensive care through the lens of services needed by children and youth (0-25 years) and community-dwelling older adults (≥ 65 years) with high functional health needs. This article describes five projects. The following three findings emerged across all the projects: Canada indeed has multiple health systems; numerous integrated service delivery solutions are being trialled and most focus on medical services; and it is an ongoing challenge for ministries of health to engage physicians and physician associations in integration.

Inconsistent Governance Structures for Health and Social Services Limit Service Integration for Patients with Complex Care Needs.

This paper describes how health and social services are governed and organized across Canada for two patient groups. Governance configurations and governance proximity between primary care and priority health and social services varied markedly between provinces. While the need for integrated service delivery has been made a clear priority during the COVID-19 pandemic, the potential of Canada's healthcare systems has not yet translated into coordinated and integrated care for health services, much less for health and social services. It is time to act on the policy recommendations from commissioned reports over the past two decades that focus on comprehensive, community-based care.

Toward Comprehensive Care Integration in Canada: Delphi Process Findings from Researchers, Clinicians, Patients and Decision Makers.

Introduction: From a larger study examining policy and program information on how Canadian provinces integrate care services, this study aimed to create "priority lists" of 10-15 services that are "absolutely needed" for care integration. Methodology: A diverse group of over 50 Canadian stakeholders participated in virtual consensus-building using the nominal group technique and a modified e-Delphi method to identify services that focused on two different groups: children and youth with high functional health needs and older adults in functional decline. Results: Three lists - containing services, processes and infrastructure elements - emerged: one per tracer condition group and a consolidated list. The latter identified the following five services as top priority for primary care integration: mental health and addictions services; home care; transition between urgent-emergency-acute care; medication reconciliation in community pharmacies; and respite care. No single social service was a clear priority, but those that mitigate material deprivation emerged within the top 10. Discussion: This humble pan-Canadian study shows that priority services in health and social services are neither well integrated nor connected to primary care. It also suggests that effective policy strategizing for primary care integration for those with complex care needs may require thinking beyond the logic of services - given their siloed organization.

Have Primary Care Renewal Initiatives in Canada Increased Comprehensive Care for Patients with Complex Care Needs? Yes and No.

The First Ministers Health Accords of 2001 through 2003 (Health Canada 2006) launched the renewal of primary care toward more comprehensive care delivery models. We scanned government websites in the 10 Canadian provinces to assess how comprehensive and integrated renewal models were for health and social services in 2018. More comprehensive primary care delivery models were the norm in five out of 10 provinces. The policy approaches were: (1) expanding traditional family practice; (2) creating primary care networks; and (3) increasing the number of community health centres, which provide the broadest range of health and social care. Integration initiatives were limited to medical services. Additional financial and policy investments will be required to meet the comprehensive needs of patients with complex health and social needs at a system level.

Innovative Programs with Multi-Service Integration for Children and Youth with High Functional Health Needs.

The integration of care services and providers across the health-social-community continuum has helped improve the lives of many children and youth living with complex health conditions. Using environmental scan data, 16 promising multi-service programs were selected and analyzed qualitatively through a deliberative conversation approach. Descriptive data of analyzed programs are presented, as well as the thematic analysis results. An important program strength is its clear founding principles and engagement of patients and families. However, the scale-up of these initiatives remains a challenge unless such programs can be better financed and supported.

Integrating Health and Social Care for Community-Dwelling Older Adults: A Description of 16 Canadian Programs.

This paper describes 16 Canadian programs designed to provide integrated primary care for older adults. Publicly available data were used to identify the "what" and the "how" of integration for each program. Most programs integrated with other healthcare or medical services (vs. social services). Mechanisms of integration varied; the most common mechanism was interprofessional teams. Only 25% of the programs formally engaged with autonomous physician-led primary care practices (where most Canadians receive their primary care). Findings suggest that integrated care is a priority across Canada but also highlight how far we have to go to achieve both vertical integration within the healthcare sector (primary, secondary and tertiary services) and horizontal integration across sectors (health and social).

Lack of Publicly Available Documentation Limits Spread of Integrated Care Innovations in Canada.

As healthcare in Canada is provincially operated, the program innovations in one jurisdiction may not be readily known in other jurisdictions. We examine the availability of implementation-specific data for 30 innovative Canadian programs designed to integrate health and social services for patients with complex needs. Using publicly available data and key informant interviews, we were able to populate only ∼50% of our data collection tool (on average). Formal program evaluations were available for only ∼30% of programs. Multiple barriers exist to the compilation and verification of healthcare programs' implementation data across Canada, limiting cross-jurisdictional learning and making a comparison of programs challenging.

Patient Partners Respond to High-Level Findings on the Connectedness of Health and Social Services across Canada.

This short article captures input from patient partners on the dimensions of the research program that most resonated with them. They are passionate about wanting to see a better connection between health and social services, and they are also willing to be involved as advisors for policy directions in the same way as their involvement has become the norm in any patient-oriented research.

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA). METHODS: Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG. RESULTS: Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p = 0.004). SIGNIFICANCE: Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

A longitudinal multi-site evaluation of community-based partnerships: implications for researchers, funders, and communities.

BACKGROUND: Innovative Models Promoting Access to Care Transformation (IMPACT) was a five-year (2013-2018), Canadian-Australian research program that aimed to use a community-based partnership approach to transform primary health care (PHC) organizational structures to improve access to appropriate care for vulnerable populations. Local Innovation Partnerships (LIPs) were developed to support the IMPACT research program, and to be ongoing structures that would continue to drive local improvements to PHC. METHODS: A longitudinal development-focused evaluation explored the overall approach to governance, relationships and processes of the LIPs in the IMPACT program. Semi-structured interviews were conducted with purposively selected participants including researchers with implementation roles and non-researchers who were members of LIPs at four time points: early in the development of the LIPs in 2014; during intervention development in 2015/2016; at the intervention implementation phase in 2017; and nearing completion of the research program in 2018.  A hybrid deductive-inductive thematic analysis approach was used. A Guide developed to support the program was used as the framework for designing questions and analysing data using a qualitative descriptive method initially. A visual representation was developed and refined after each round of data collection to illustrate emerging themes around governance, processes and relationship building that were demonstrated by IMPACT LIPs. After all rounds of data collection, an overarching cross-case analysis of narrative summaries of each site was conducted. RESULTS: Common components of the LIPs identified across all rounds of data collection related to governance structures, stakeholder relationships, collaborative processes, and contextual barriers.  LIPs were seen primarily as a structure to support implementation of a research project rather than an ongoing multisectoral community-based partnership.  LIPs had relationships with many and varied stakeholders although not necessarily in ways that reflected the intended purpose. Collaboration was valued, but multiple barriers impeded the ability of LIPs to enact real collaboration in daily operations over time. We learned that experience, history, and time matter, especially with respect to community-oriented collaborative skills, structures, and relationships. CONCLUSIONS: This longitudinal multiple case study offers lessons and implications for researchers, funders, and potential stakeholders in community-based participatory research.

Identifying and troubleshooting the pitfalls of ictal/interictal brain perfusion SPECT studies.

Epilepsy is a prevalent condition, and surgical intervention can benefit patients with refractory seizures. Single photon emission computed tomography (SPECT) using 99mTc-HMPAO or 99mTc-ECD provides assessment of regional cerebral blood flow and is the primary non-invasive approach for imaging brain perfusion in ictal and interictal states. Ictal/interictal SPECT is valuable in localising epileptogenic foci, particularly when MRI and electroencephalography are negative. However, to obtain accurate images reflecting brain perfusion in both states, meticulous preparation of the patient, timely radiotracer injection and close coordination between neurology and nuclear medicine teams are essential. Tracers also have inherent limitations, and patients may present with coexisting brain pathologies for which coregistration of SPECT images with MRI is recommended to improve diagnostic accuracy. Inconclusive SPECT findings may require repeating the exam or considering additional investigations. A comprehensive approach, considering various factors, is crucial for accurate interpretation of SPECT studies in presurgical epilepsy evaluations. This article provides a summary of the organisation and key challenges involved in conducting ictal/interictal SPECT studies, covering the entire process from a patient's hospital arrival to the integration of results within their presurgical pathway and using our experience of 182 patients over 10 years.

Brain PET and SPECT imaging and quantification: a survey of the current status in the UK.

OBJECTIVES: With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. METHODS: A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. RESULTS: Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitative Brain analysis is used in 86% of sites performing DaTscans, 40% for Perfusion SPECT, 63% for FDG PET and 42% for Amyloid PET. Commercial tools are used more frequently than in-house software. CONCLUSION: The survey showed variations across the UK, with high availability of DaTscan imaging and quantification and lower availability of other SPECT and PET scans. The main drivers for quantification were improved reporting confidence and diagnostic accuracy, while the main barriers were a perception of a need for an appropriate database of healthy controls and a lack of training, time, and software availability.