Diminished circadian and ultradian rhythms of human brain activity in pathological tissue in vivo.

Chronobiological rhythms, such as the circadian rhythm, have long been linked to neurological disorders, but it is currently unknown how pathological processes affect the expression of biological rhythms in the brain. Here, we use the unique opportunity of long-term, continuous intracranially recorded EEG from 38 patients (totalling 6338 hours) to delineate circadian (daily) and ultradian (minute to hourly) rhythms in different brain regions. We show that functional circadian and ultradian rhythms are diminished in pathological tissue, independent of regional variations. We further demonstrate that these diminished rhythms are persistent in time, regardless of load or occurrence of pathological events. These findings provide evidence that brain pathology is functionally associated with persistently diminished chronobiological rhythms in vivo in humans, independent of regional variations or pathological events. Future work interacting with, and restoring, these modulatory chronobiological rhythms may allow for novel therapies.

The influence of temperature and genomic variation on intracranial EEG measures in people with epilepsy.

Heatwaves have serious impacts on human health and constitute a key health concern from anthropogenic climate change. People have different individual tolerance for heatwaves or unaccustomed temperatures. Those with epilepsy may be particularly affected by temperature as the electroclinical hallmarks of brain excitability in epilepsy (inter-ictal epileptiform discharges and seizures) are influenced by a range of physiological and non-physiological conditions. Heatwaves are becoming more common and may affect brain excitability. Leveraging spontaneous heatwaves during periods of intracranial EEG recording in participants with epilepsy in a non-air-conditioned telemetry unit at the National Hospital for Neurology and Neurosurgery in London from May to August 2015-22, we examined the impact of heatwaves on brain excitability. In London, a heatwave is defined as three or more consecutive days with daily maximum temperatures ≥28°C. For each participant, we counted inter-ictal epileptiform discharges using four 10-min segments within, and outside of, heatwaves during periods of intracranial EEG recording. Additionally, we counted all clinical and subclinical seizures within, and outside of, heatwaves. We searched for causal rare genetic variants and calculated the epilepsy PRS. Nine participants were included in the study (six men, three women), median age 30 years (range 24-39). During heatwaves, there was a significant increase in the number of inter-ictal epileptiform discharges in three participants. Five participants had more seizures during the heatwave period, and as a group, there were significantly more seizures during the heatwaves. Genetic data, available for eight participants, showed none had known rare, genetically-determined epilepsies, whilst all had high polygenic risk scores for epilepsy. For some people with epilepsy, and not just those with known, rare, temperature-sensitive epilepsies, there is an association between heatwaves and increased brain excitability. These preliminary data require further validation and exploration, as they raise concerns about the impact of heatwaves directly on brain health.

Incidence of Hospitalization due to Influenza-Associated Severe Acute Respiratory Infection During 2010-2019 in Bangladesh.

BACKGROUND: Global influenza-associated acute respiratory infections contribute to 3-5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children < 5 years in developing countries. In Bangladesh, the inadequate availability of nationally representative, robust estimates of influenza-associated hospitalizations limits allocation of resources for prevention and control measures. METHODS: This study used data from the hospital-based influenza surveillance (HBIS) system in Bangladesh from 2010 to 2019 and healthcare utilization surveys to determine hospital utilization patterns in the catchment area. We estimated annual influenza-associated hospitalization numbers and rates for all age groups in Bangladesh using WHO methods, adjusted for a 6-day-a-week enrollment schedule, selective testing of specimens from children under five, and healthcare-seeking behavior, based on the proportion of symptomatic community participants seeking healthcare within the past week. We then estimated national hospitalization rates by multiplying age-specific hospitalization rates with the corresponding annual national census population. RESULTS: Annual influenza-associated hospitalization rates per 100,000 population for all ages ranged from 31 (95% CI: 27-36) in 2011 to 139 (95% CI: 130-149) in 2019. Children < 5 years old had the highest rates of influenza-associated hospitalization, ranging from 114 (95% CI: 90-138) in 2011 to 529 (95% CI: 481-578) in 2019, followed by adults aged ≥ 65 years with rates ranging from 46 (95% CI: 34-57) in 2012 to 252 (95% CI: 213-292) in 2019. The national hospitalization estimates for all ages during 2010-2019 ranged from 47,891 to 236,380 per year. CONCLUSIONS: The impact of influenza-associated hospitalizations in Bangladesh may be considerable, particularly for young children and older adults. Targeted interventions, such as influenza vaccination for these age groups, should be prioritized and evaluated.

Cost-effectiveness of seasonal influenza vaccination in WHO-defined high-risk populations in Bangladesh.

Background: Bangladesh carries a substantial health and economic burden of seasonal influenza, particularly among the World Health Organization (WHO)-defined high-risk populations. We implemented a modelling study to determine the cost-effectiveness of influenza vaccination in each of five high-risk groups (pregnant women, children under five years of age, adults with underlying health conditions, older adults (≥60 years), and healthcare personnel) to inform policy decisions on risk group prioritisation for influenza vaccination in Bangladesh. Methods: We implemented a Markov decision-analytic model to estimate the impact of influenza vaccination for each target risk group. We obtained model inputs from hospital-based influenza surveillance data, unpublished surveys, and published literature (preferentially from studies in Bangladesh, followed by regional and global ones). We used quality-adjusted life years (QALY) as the health outcome of interest. We also estimated incremental cost-effectiveness ratios (ICERs) for each risk group by comparing the costs and QALY of vaccinating compared to not vaccinating each group, where the ICER represents the additional cost needed to achieve one year of additional QALY from a given intervention. We considered a willingness-to-pay threshold (ICER) of less than one gross domestic product (GDP) per capita as highly cost-effective and of one to three times GDP per capita as cost-effective (per WHO standard). For Bangladesh, this threshold ranges between USD 2462 and USD 7386. Results: The estimated ICERs were USD -99, USD -87, USD -4, USD 792, and USD 229 per QALY gained for healthcare personnel, older adults (≥60), children aged less than five years, adults with comorbid conditions, and pregnant women, respectively. For all risk groups, ICERs were below the WHO willingness-to-pay threshold for Bangladesh. Vaccinating pregnant women and adults with comorbid conditions was highly cost-effective per additional life year gained, while vaccinating healthcare personnel, older adults (≥60), and children under five years were cost-saving per additional life year gained. Conclusions: Influenza vaccination to all target risk groups in Bangladesh would be either cost-saving or cost-effective, per WHO guidelines of GDP-based thresholds.

Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.

Post-discharge mortality among patients hospitalised with severe acute respiratory infection, Bangladesh, 2012-2019: a prospective observational study.

Background: Enhancing outcomes post-hospitalisation requires an understanding of predictive factors for adverse events. This study aimed to estimate post-discharge mortality rates among patients with severe acute respiratory infection (SARI) in Bangladesh, identify associated factors, and document reported causes of death. Methods: From January 2012 to December 2019, we conducted follow-up calls to patients or their families 30 days after discharge to assess the status of patients with SARI. Proportions of deaths within 30 days of discharge were estimated, and a comparative analysis of demographics, clinical characteristics, and influenza illness between decedents and survivors was performed using multivariable Cox regression models. Findings: Among 23,360 patients with SARI (median age: 20 years, IQR: 1.5-48, 65% male), 351 (1.5%) died during hospitalisation. Of 23,009 patients alive at discharge, 20,044 (87%) were followed, with 633 (3.2%) deaths within 30 days of discharge. In children (<18 years), difficulty breathing (adjusted hazard ratio [aHR] 1.8; 95% CI 1.1-3.0), longer hospital stay (aHR 1.1; 95% CI 1.1-1.1), and heart diseases (aHR 8.5; 95% CI 3.2-23.1) were associated with higher post-discharge death risk. Among adults (≥18 years), difficulty breathing (aHR 2.3; 95% CI 1.7-3.0), chronic obstructive pulmonary disease (aHR 1.7; 95% CI 1.4-2.2), and intensive care unit admission (aHR 5.2; 95% CI 1.9-14.0) were linked to elevated post-discharge death risk. Influenza virus was detected in 13% (46/351) of in-hospital SARI deaths and 10% (65/633) of post-discharge SARI deaths. Interpretation: Nearly one in twenty patients with SARI died during hospitalisation or within 1 month of discharge, with two-thirds of deaths occurring post-discharge. Seasonal influenza vaccination is recommended to mitigate influenza-associated mortality. To enhance post-discharge outcomes, hospitals should consider developing safe-discharge algorithms, reinforcing post-discharge care plans, and establishing outpatient monitoring for recently discharged patients. Funding: Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA [U01GH002259].

Prevalence of influenza and other acute respiratory illnesses in patients with acute myocardial infarction in Bangladesh: A cross-sectional study.

Background and Aims: Several studies imply that influenza and other respiratory illnesses could lead to acute myocardial infarction (AMI), but data from low-income countries are scarce. We investigated the prevalence of recent respiratory illnesses and confirmed influenza in AMI patients, while also exploring their relationship with infarction severity as defined by ST-elevation MI (STEMI) or high troponin levels. Methods: This cross-sectional study, held at a Dhaka tertiary hospital from May 2017 to October 2018, involved AMI inpatients. The study examined self-reported clinical respiratory illnesses (CRI) in the week before AMI onset and confirmed influenza using baseline real-time reverse transcription polymerase chain reaction (qRT-PCR). Results: Of 744 patients, 11.3% reported a recent CRI, most prominently during the 2017 influenza season (35.7%). qRT-PCR testing found evidence of influenza in 1.5% of 546 patients, with all positives among STEMI cases. Frequencies of CRI were higher in patients with STEMI and in those with high troponin levels, although these relationships were not statistically significant after adjusting for other variables. The risk of STEMI was significantly greater during influenza seasons in the unadjusted analysis (relative risk: 1.09, 95% confidence interval [CI]: 1.02-1.18), however, this relationship was not significant in the adjusted analysis (adjusted relative risk: 1.03, 95% CI: 0.91-1.16). Conclusion: In Bangladesh, many AMI patients had a recent respiratory illness history, with some showing evidence of influenza. However, these illnesses showed no significant relationship to AMI severity. Further research is needed to understand these relationships better and to investigate the potential benefits of infection control measures and influenza vaccinations in reducing AMI incidence.

Emergence of the novel sixth Candida auris Clade VI in Bangladesh.

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.

Complicated epilepsy surgery: importance of balancing benefit and deficit.

The risk-benefit ratio of epilepsy surgery needs careful consideration, is different for each individual and requires a careful, informed dialogue between the person concerned and their medical advisers. We illustrate this process with Virginia, who has had refractory focal epilepsy from age 1 year and a left hemiparesis. At the age of 45 years, we discussed the possibility of epilepsy surgery and went through non-invasive investigations with structural and functional MRI, tractography, scalp video-EEG telemetry, neuropsychological and neuropsychiatric evaluations. This was followed by a decision to carry out intracranial EEG to define the area of seizure onset and its relation to an area of focal cortical dysplasia, eloquent cortex and tracts. We agreed to carry out a focal resection in the knowledge that this would result in a loss of left-hand function. One year later, Virginia is seizure-free on reduced medication. We describe the steps in the process with Virginia's views.

Characteristics of Hospitalized COVID-19 Patients at Admission and Factors Associated with Clinical Severity in Low- and Middle-Income Countries: An Observational Study.

Despite the numerous articles published on the clinical characteristics and outcomes of COVID-19 with regard to high-income countries, little is known about patients in low- and middle-income countries (LMIC) in this context. The objective of this observational, prospective, hospital-based multicentric study was to describe clinical features and outcomes of laboratory-confirmed COVID-19 patients hospitalized in each of the participating centers in Bangladesh, Guinea, Ivory Coast, Lebanon, Madagascar, and Mali during the first year of the pandemic (March 5, 2020 to May 4, 2021). The study outcome was the clinical severity of COVID-19, defined as hospitalization in intensive care unit or death. Multivariate logistic regression models were performed to identify independent variables associated with disease severity. Overall, 1,096 patients were included. The median age was 49.0 years, ranging from 38.0 in Mali to 63.0 years in Guinea. The overall clinical severity of COVID-19 was 12.3%, ranging from 6.4% in Mali to 18.8% in Guinea. In both groups of patients <60 and ≥60 years old, cardiovascular diseases (adjusted odds ratio [aOR]: 1.99; 95% CI: 1.13-3.50, P = 0.02; aOR: 2.47; 95% CI: 1.33-4.57, P = 0.004) were independently associated with clinical severity, whereas in patients <60 years, diabetes (aOR: 2.13; 95% CI: 1.11-4.10, P = 0.02) was also associated with clinical severity. Our findings suggest that COVID-19-related severity and death in LMICs are mainly driven by older age. However, the presence of chronic diseases can also increase the risk of severity especially in younger patients.

Respiratory Syncytial Virus-Associated Deaths among Children under Five before and during the COVID-19 Pandemic in Bangladesh.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children worldwide. RSV-associated deaths in children are underreported in Bangladesh. We analyzed hospital-based surveillance data on severe acute respiratory infections (SARIs) in under-five children before (August 2009-February 2020) and during the COVID-19 pandemic (March 2020-March 2022). Using the World Health Organization definition, we identified SARI cases in 14 tertiary-level hospitals. Nasopharyngeal and oropharyngeal swabs were collected for real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) testing of six respiratory viruses, including RSV. SARI deaths during the pandemic (2.6%, 66) were higher than pre-pandemic (1.8%, 159; p < 0.001). Nearly half of pandemic deaths (47%) had underlying respiratory viruses, similar to the pre-pandemic rate (45%). RSV detection in deaths was consistent pre-pandemic (13%, 20/159) and during the pandemic (12%, 8/66). Children aged < 6 months constituted 57% (16) of RSV-related deaths. Evaluating interventions like maternal vaccination and infant monoclonal antibody prophylaxis is crucial to address RSV, a major contributor to under-five SARI deaths.

Acceptability, cost-effectiveness, and capacity of a facility-based seasonal influenza vaccination among high-risk groups: a study protocol in selected tertiary care hospitals of Bangladesh.

BACKGROUND: In Bangladesh, seasonal influenza imposes considerable disease and economic burden, especially for those at high-risk of severe disease. The most successful approach for influenza prevention is the administration of a vaccine. Many poor and middle-income nations, including Bangladesh, do not have a national strategy or program in place for seasonal influenza vaccines, despite the World Health Organization's (WHO) advice to prioritize high-risk populations. Additionally, there is a scarcity of substantial data on the cost-effectiveness of seasonal influenza vaccination in these countries. The aim of our study is to determine acceptability, health beliefs, barriers, and intention of receiving influenza vaccine among high-risk populations, assess the cost-effectiveness of implementing a facility-based seasonal influenza vaccination programme, and investigate the required capacity for a potential seasonal influenza vaccination programme. METHODS: We will undertake this study following STROBE guidelines. We will conduct the study in inpatient and outpatient departments of three selected tertiary-level hospitals leveraging the ongoing hospital-based influenza surveillance (HBIS) platform. The study population will include the WHO-defined four high-risk groups excluding healthcare workers: children six months to eight years, pregnant women, elderly ≥ 60 years, and adults with chronic diseases. We will collect quantitative data on participants' acceptability, health beliefs, barriers, and vaccination intentions using the health belief model (HBM) from patients meeting the criteria for high-risk populations attending two public tertiary-level hospitals. In one of the two public tertiary-level hospitals, we will arrange an influenza vaccination campaign before the influenza season, where the vaccine will be offered free of cost to high-risk patients, and in the second hospital, vaccination will not be offered. Both the vaccinated and unvaccinated participants will then be followed-up once a month for one year to record any influenza-like illness, hospitalization, and death. Additional data for objective two will be collected from patients with symptoms of influenza-like illness (ILI) and severe acute respiratory infection (SARI) at one public and one private hospital to determine both direct and indirect costs associated with influenza illness. We will estimate the required number of influenza vaccines, safe injections, and total storage volume utilizing secondary data. We will use a deterministic Markov decision-analytic model to estimate the cost-effectiveness of facility-based influenza vaccination in Bangladesh. DISCUSSION: The results of this study will enable the National Immunization Technical Advisory Group and the Ministry of Health & Family Welfare of Bangladesh to decide what steps to take to develop and implement an influenza vaccination strategy targeting high-risk populations. TRIAL REGISTRATION: The Clinicaltrials.gov registration number is NCT05996549. The registration for the protocol version 2.0 took place in August 2023, with the initial participant being enrolled in March 2022.

Cerebral folate deficiency: a treatable cause of late deterioration in epilepsy with developmental delay.

A 25-year-old woman with childhood-onset refractory epilepsy and developmental delay experienced a gradually progressive marked deterioration in mobility and seizure control, with language regression. Investigation identified a homozygous deletion within the contactin-associated protein-like 2 gene (CNTNAP2), underlying her early presentation, but also cerebral folate deficiency that most likely contributed to her later deterioration. Following antiseizure medication adjustment and treatment with folinic acid, she stabilised with improved seizure control and limited improvement in language and motor function; she has remained neurologically stable for more than a decade. That the previously observed neurological decline was halted by folinic acid replacement supports this being due to cerebral folate deficiency. Metabolic conditions are less well recognised in adults and can be under-diagnosed. They are potentially treatable and should be considered even in the presence of another cause, particularly when the presentation is not fully compatible.

Characterizing deaths among adult patients with severe acute respiratory infection: during the pre- and COVID-19 pandemic periods in Bangladesh, 2018-2022.

BACKGROUND: Severe acute respiratory infection (SARI) is a leading cause of mortality globally, peaking during the COVID-19 pandemic. We analyzed SARI-associated deaths during the pre-and-pandemic periods in Bangladesh to identify the contributing factors. METHODS: We analyzed data from hospital-based influenza surveillance at nine tertiary-level hospitals in Bangladesh. We considered March 2018-February 2020 as the pre-pandemic period and March 2020-February 2022 as the pandemic period and included adult (≥ 18 years) participants in our study. Surveillance physicians identified WHO-SARI case definition meeting inpatients and collected demographics, clinical characteristics, and outcomes at hospital discharge and 30 days post-discharge. We performed rRT-PCR for influenza and SARS-CoV-2 viruses on collected nasopharyngeal and oropharyngeal swabs. We used multivariable Cox's regression models to calculate the hazard ratio (HR) for factors associated with SARI deaths in these adult patients. RESULTS: We enrolled 4392 SARI patients during the pre-pandemic and 3824 SARI patients during the pandemic period. Case fatality ratio was higher during the pandemic: 13.62% (521) [in-hospital: 6.45% (247); post-discharge: 7.17% (274)] compared to pre-pandemic, 6.01% (264) [in-hospital: 2.01% (89), post-discharge: 4% (175)] (p < 0.001). Pre-pandemic, influenza was detected in 14% (37/264) of SARI deaths. Influenza was detected during the pandemic in 2.3% (12/521), SARS-CoV-2 in 41.8% (218/521), and both viruses in only one SARI death. History of smoking and the presence of 1 or more co-morbid conditions independently attributed to SARI deaths in adults in the pre-pandemic period. SARI deaths in such patients were also associated with respiratory difficulties on admission in both pre-pandemic (aHR 2.36; 95% CI:1.65-3.36) and pandemic period (aHR 2.30; 95% CI: 1.57-3.35) after accounting for age, sex, smoking status, presence of 1 or more co-morbid conditions, and detection of influenza and SARS-CoV-2 viruses. CONCLUSIONS: During the pandemic, SARI mortality increased; influenza-associated mortality declined, and SARS-CoV-2 caused over a third of SARI deaths. Post-discharge mortality was higher than in-hospital mortality during both periods. Limiting premature discharge and strengthening post-discharge monitoring and nursing services could reduce unexpected deaths. Formative research to better understand post-discharge mortality is essential to reduce SARI deaths.

Wake slow waves in focal human epilepsy impact network activity and cognition.

Slow waves of neuronal activity are a fundamental component of sleep that are proposed to have homeostatic and restorative functions. Despite this, their interaction with pathology is unclear and there is only indirect evidence of their presence during wakefulness. Using intracortical recordings from the temporal lobe of 25 patients with epilepsy, we demonstrate the existence of local wake slow waves (LoWS) with key features of sleep slow waves, including a down-state of neuronal firing. Consistent with a reduction in neuronal activity, LoWS were associated with slowed cognitive processing. However, we also found that LoWS showed signatures of a homeostatic relationship with interictal epileptiform discharges (IEDs): exhibiting progressive adaptation during the build-up of network excitability before an IED and reducing the impact of subsequent IEDs on network excitability. We therefore propose an epilepsy homeostasis hypothesis: that slow waves in epilepsy reduce aberrant activity at the price of transient cognitive impairment.

Association of recent respiratory illness and influenza with acute myocardial infarction among the Bangladeshi population: A case-control study.

Current evidence suggests that recent acute respiratory infections and seasonal influenza may precipitate acute myocardial infarction (AMI). This study examined the potential link between recent clinical respiratory illness (CRI) and influenza, and AMI in Bangladesh. Conducted during the 2018 influenza season at a Dhaka tertiary-level cardiovascular (CV) hospital, it included 150 AMI cases and two control groups: 44 hospitalized cardiac patients without AMI and 90 healthy individuals. Participants were matched by gender and age groups. The study focused on self-reported CRI and laboratory-confirmed influenza ascertained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) within the preceding week, analyzed using multivariable logistic regression. Results showed that cases reported CRI, significantly more frequently than healthy controls (27.3% vs. 13.3%, adjusted odds ratio (aOR): 2.21; 95% confidence interval (CI): 1.05-4.06), although this was not significantly different from all controls (27.3% vs. 22.4%; aOR: 1.19; 95% CI: 0.65-2.18). Influenza rates were insignificantly higher among cases than controls. The study suggests that recent respiratory illnesses may precede AMI onset among Bangladeshi patients. Infection prevention and control practices, as well as the uptake of the influenza vaccine, may be advocated for patients at high risk of acute CV events.

Interictal magnetoencephalography abnormalities to guide intracranial electrode implantation and predict surgical outcome.

Intracranial EEG is the gold standard technique for epileptogenic zone localization but requires a preconceived hypothesis of the location of the epileptogenic tissue. This placement is guided by qualitative interpretations of seizure semiology, MRI, EEG and other imaging modalities, such as magnetoencephalography. Quantitative abnormality mapping using magnetoencephalography has recently been shown to have potential clinical value. We hypothesized that if quantifiable magnetoencephalography abnormalities were sampled by intracranial EEG, then patients' post-resection seizure outcome may be better. Thirty-two individuals with refractory neocortical epilepsy underwent magnetoencephalography and subsequent intracranial EEG recordings as part of presurgical evaluation. Eyes-closed resting-state interictal magnetoencephalography band power abnormality maps were derived from 70 healthy controls as a normative baseline. Magnetoencephalography abnormality maps were compared to intracranial EEG electrode implantation, with the spatial overlap of intracranial EEG electrode placement and cerebral magnetoencephalography abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue and subsequent resection of the strongest abnormalities determined by magnetoencephalography and intracranial EEG corresponded to surgical success. We used the area under the receiver operating characteristic curve as a measure of effect size. Intracranial electrodes were implanted in brain tissue with the most abnormal magnetoencephalography findings-in individuals that were seizure-free postoperatively (T = 3.9, P = 0.001) but not in those who did not become seizure-free. The overlap between magnetoencephalography abnormalities and electrode placement distinguished surgical outcome groups moderately well (area under the receiver operating characteristic curve = 0.68). In isolation, the resection of the strongest abnormalities as defined by magnetoencephalography and intracranial EEG separated surgical outcome groups well, area under the receiver operating characteristic curve = 0.71 and area under the receiver operating characteristic curve = 0.74, respectively. A model incorporating all three features separated surgical outcome groups best (area under the receiver operating characteristic curve = 0.80). Intracranial EEG is a key tool to delineate the epileptogenic zone and help render individuals seizure-free postoperatively. We showed that data-driven abnormality maps derived from resting-state magnetoencephalography recordings demonstrate clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Additionally, our predictive model of postoperative seizure freedom, which leverages both magnetoencephalography and intracranial EEG recordings, could aid patient counselling of expected outcome.

Complementary structural and functional abnormalities to localise epileptogenic tissue.

BACKGROUND: When investigating suitability for epilepsy surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation of the epileptogenic zone (EZ), improving surgical outcomes in epilepsy. METHODS: We retrospectively investigated data from 43 patients (42% female) with epilepsy who had surgery following iEEG. Twenty-five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls. We explored whether the resection of maximal abnormalities related to improved surgical outcomes, in both modalities individually and concurrently. Additionally, we suggest how connectivity abnormalities may inform the placement of iEEG electrodes pre-surgically using a patient case study. FINDINGS: Seizure freedom was 15 times more likely in patients with resection of maximal connectivity and iEEG abnormalities (p = 0.008). Both modalities separately distinguished patient surgical outcome groups and when used simultaneously, a decision tree correctly separated 36 of 43 (84%) patients. INTERPRETATION: Our results suggest that both connectivity and iEEG abnormalities may localise epileptogenic tissue, and that these two modalities may provide complementary information in pre-surgical evaluations. FUNDING: This research was funded by UKRI, CDT in Cloud Computing for Big Data, NIH, MRC, Wellcome Trust and Epilepsy Research UK.

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.

Lessons learned from identifying clusters of severe acute respiratory infections with influenza sentinel surveillance, Bangladesh, 2009-2020.

Background: We explored whether hospital-based surveillance is useful in detecting severe acute respiratory infection (SARI) clusters and how often these events result in outbreak investigation and community mitigation. Methods: During May 2009-December 2020, physicians at 14 sentinel hospitals prospectively identified SARI clusters (i.e., ≥2 SARI cases who developed symptoms ≤10 days of each other and lived <30 min walk or <3 km from each other). Oropharyngeal and nasopharyngeal swabs were tested for influenza and other respiratory viruses by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We describe the demographic of persons within clusters, laboratory results, and outbreak investigations. Results: Field staff identified 464 clusters comprising 1427 SARI cases (range 0-13 clusters per month). Sixty percent of clusters had three, 23% had two, and 17% had ≥4 cases. Their median age was 2 years (inter-quartile range [IQR] 0.4-25) and 63% were male. Laboratory results were available for the 464 clusters with a median of 9 days (IQR = 6-13 days) after cluster identification. Less than one in five clusters had cases that tested positive for the same virus: respiratory syncytial virus (RSV) in 58 (13%), influenza viruses in 24 (5%), human metapneumovirus (HMPV) in five (1%), human parainfluenza virus (HPIV) in three (0.6%), adenovirus in two (0.4%). While 102/464 (22%) had poultry exposure, none tested positive for influenza A (H5N1) or A (H7N9). None of the 464 clusters led to field deployments for outbreak response. Conclusions: For 11 years, none of the hundreds of identified clusters led to an emergency response. The value of this event-based surveillance might be improved by seeking larger clusters, with stronger epidemiologic ties or decedents.