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.

Orienting to fear under transient focal disruption of the human amygdala.

Responding to threat is under strong survival pressure, promoting the evolution of systems highly optimized for the task. Though the amygdala is implicated in 'detecting' threat, its role in the action that immediately follows-'orienting'-remains unclear. Critical to mounting a targeted response, such early action requires speed, accuracy, and resilience optimally achieved through conserved, parsimonious, dedicated systems, insured against neural loss by a parallelized functional organization. These characteristics tend to conceal the underlying substrate not only from correlative methods but also from focal disruption over time scales long enough for compensatory adaptation to take place. In a study of six patients with intracranial electrodes temporarily implanted for the clinical evaluation of focal epilepsy, we investigated gaze orienting to fear during focal, transient, unilateral direct electrical disruption of the amygdala. We showed that the amygdala is necessary for rapid gaze shifts towards faces presented in the contralateral hemifield regardless of their emotional expression, establishing its functional lateralization. Behaviourally dissociating the location of presented fear from the direction of the response, we implicated the amygdala not only in detecting contralateral faces, but also in automatically orienting specifically towards fearful ones. This salience-specific role was demonstrated within a drift-diffusion model of action to manifest as an orientation bias towards the location of potential threat. Pixel-wise analysis of target facial morphology revealed scleral exposure as its primary driver, and induced gamma oscillations-obtained from intracranial local field potentials-as its time-locked electrophysiological correlate. The amygdala is here reconceptualized as a functionally lateralized instrument of early action, reconciling previous conflicting accounts confined to detection, and revealing a neural organisation analogous to the superior colliculus, with which it is phylogenetically kin. Greater clarity on its role has the potential to guide therapeutic resection, still frequently complicated by impairments of cognition and behaviour related to threat, and inform novel focal stimulation techniques for the management of neuropsychiatric conditions.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

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.

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.

Prevalence of Colonization With Antibiotic-Resistant Organisms in Hospitalized and Community Individuals in Bangladesh, a Phenotypic Analysis: Findings From the Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance (AMR) but often lack adequate surveillance to inform mitigation efforts. Colonization can be a useful metric to understand AMR burden. We assessed the colonization prevalence of Enterobacterales with resistance to extended-spectrum cephalosporins, carbapenems, colistin, and methicillin-resistant Staphylococcus aureus among hospital and community dwellers. METHODS: Between April and October 2019, we conducted a period prevalence study in Dhaka, Bangladesh. We collected stool and nasal specimens from adults in 3 hospitals and from community dwellers within the hospitals' catchment area. Specimens were plated on selective agar plates. Isolates underwent identification and antibiotic susceptibility testing using Vitek 2. We performed descriptive analysis and determined population prevalence estimates accounting for clustering at the community level. RESULTS: The majority of both community and hospital participants were colonized with Enterobacterales with resistance to extended-spectrum cephalosporins (78%; 95% confidence interval [95% CI], 73-83; and 82%; 95% CI, 79-85, respectively). Thirty-seven percent (95% CI, 34-41) of hospitalized patients were colonized with carbapenems compared with 9% (95% CI, 6-13) of community individuals. Colistin colonization prevalence was 11% (95% CI, 8-14) in the community versus 7% (95% CI, 6-10) in the hospital. Methicillin-resistant Staphylococcus aureus colonization was similar in both community and hospital participants (22%; 95% CI, 19-26 vs 21% (95% CI, 18-24). CONCLUSIONS: The high burden of AMR colonization observed among hospital and community participants may increase the risk for developing AMR infections and facilitating spread of AMR in both the community and hospital.

Temporal stability of intracranial electroencephalographic abnormality maps for localizing epileptogenic tissue.

OBJECTIVE: Identifying abnormalities on interictal intracranial electroencephalogram (iEEG), by comparing patient data to a normative map, has shown promise for the localization of epileptogenic tissue and prediction of outcome. The approach typically uses short interictal segments of approximately 1 min. However, the temporal stability of findings has not been established. METHODS: Here, we generated a normative map of iEEG in nonpathological brain tissue from 249 patients. We computed regional band power abnormalities in a separate cohort of 39 patients for the duration of their monitoring period (.92-8.62 days of iEEG data, mean = 4.58 days per patient, >4800 hours recording). To assess the localizing value of band power abnormality, we computed D RS -a measure of how different the surgically resected and spared tissue was in terms of band power abnormalities-over time. RESULTS: In each patient, the D RS value was relatively consistent over time. The median D RS of the entire recording period separated seizure-free (International League Against Epilepsy [ILAE] = 1) and not-seizure-free (ILAE > 1) patients well (area under the curve [AUC] = .69). This effect was similar interictally (AUC = .69) and peri-ictally (AUC = .71). SIGNIFICANCE: Our results suggest that band power abnormality D_RS, as a predictor of outcomes from epilepsy surgery, is a relatively robust metric over time. These findings add further support for abnormality mapping of neurophysiology data during presurgical evaluation.

A library of quantitative markers of seizure severity.

OBJECTIVE: Understanding fluctuations in seizure severity within individuals is important for determining treatment outcomes and responses to therapy, as well as assessing novel treatments for epilepsy. Current methods for grading seizure severity rely on qualitative interpretations from patients and clinicians. Quantitative measures of seizure severity would complement existing approaches to electroencephalographic (EEG) monitoring, outcome monitoring, and seizure prediction. Therefore, we developed a library of quantitative EEG markers that assess the spread and intensity of abnormal electrical activity during and after seizures. METHODS: We analyzed intracranial EEG (iEEG) recordings of 1009 seizures from 63 patients. For each seizure, we computed 16 markers of seizure severity that capture the signal magnitude, spread, duration, and postictal suppression of seizures. RESULTS: Quantitative EEG markers of seizure severity distinguished focal versus subclinical seizures across patients. In individual patients, 53% had a moderate to large difference (rank sum r > .3 , p < .05 ) between focal and subclinical seizures in three or more markers. Circadian and longer term changes in severity were found for the majority of patients. SIGNIFICANCE: We demonstrate the feasibility of using quantitative iEEG markers to measure seizure severity. Our quantitative markers distinguish between seizure types and are therefore sensitive to established qualitative differences in seizure severity. Our results also suggest that seizure severity is modulated over different timescales. We envisage that our proposed seizure severity library will be expanded and updated in collaboration with the epilepsy research community to include more measures and modalities.

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.

Normative brain mapping of interictal intracranial EEG to localize epileptogenic tissue.

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localizing epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 participants (21 598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We proposed that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures postoperatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions that were spared by surgery were more abnormal than those resected only in patients with persistent postoperative seizures (t = -3.6, P = 0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (area under curve 0.75 P = 0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyond.

Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy.

Personalized medicine requires that treatments adapt to not only the patient but also changing factors within each individual. Although epilepsy is a dynamic disorder characterized by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network evolutions using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures per patient). In all patients, we found variability in seizure paths through the space of possible network dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure evolutions, leading to variable seizure pathways that may require tailored treatment approaches.

Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene.

POLD1 (DNA polymerase delta 1, catalytic subunit) is a protein-coding gene that encodes the large catalytic subunit (POLD1/p125) of the DNA polymerase delta (Polδ) complex. The consequence of missense or nonsynonymous SNPs (nsSNPs), which occur in the coding region of a specific gene, is the replacement of single amino acid. It may also change the structure, stability, and/or functions of the protein. Mutation in the POLD1 gene is associated with autosomal dominant predisposition to colonic adenomatous polyps, colon cancer, endometrial cancer (EDMC), breast cancer, and brain tumors. These de novo mutations in the POLD1 gene also result in autosomal dominant MDPL syndrome (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy). In this study, genetic variations of POLD1 which may affect the structure and/or function were analyzed using different types of bioinformatics tools. A total of 17038 nsSNPs for POLD1 were collected from the NCBI database, among which 1317 were missense variants. Out of all missense nsSNPs, 28 were found to be deleterious functionally and structurally. Among these deleterious nsSNPs, 23 showed a conservation scale of >5, 2 were predicted to be associated with binding site formation, and one acted as a posttranslational modification site. All of them were involved in coil, extracellular structures, or helix formation, and some cause the change in size, charge, and hydrophobicity.

Seasonal influenza vaccine uptake among healthcare workers in tertiary care hospitals, Bangladesh: Study protocol for influenza vaccine supply and awareness intervention.

BACKGROUND: Healthcare workers (HCWs), such as doctors, nurses, and support staffs involved in direct or indirect patient care, are at increased risk of influenza virus infections due to occupational exposures. Vaccination is the most effective way to prevent influenza. Despite the World Health Organization (WHO) recommendations, Bangladesh lacks a seasonal influenza vaccination policy for HCWs, and thus vaccination rates remain low. The current project aims to investigate the effect of interventions on influenza vaccine awareness and availability of vaccine supply, explore HCWs' knowledge and perceptions about influenza vaccination, understand the barriers and motivators for influenza vaccine uptake, and understand policymakers' views on the practicality of influenza vaccination among HCWs. METHOD: We will conduct the study at four tertiary care teaching hospitals in Bangladesh, using a cluster randomized controlled trial approach, with the hospital as the unit of randomization and intervention. The study population will include all types of HCWs.The four different types of intervention will be randomly allocated and implemented in four study hospitals separately. The four interventions will be: i) ensuring the availability of influenza vaccine supply; ii) developing influenza vaccine awareness; iii) both ensuring influenza vaccine supply and developing influenza vaccine awareness and iv) control arm with no intervention. Both quantitative and qualitative approaches will be applied to assess the intervention effect. We will estimate the Difference in Differences (DID) with 95% CI of the proportion of vaccine uptake between each intervention and control (non-intervention) arm, adjusting for the clustering effect. The qualitative data will be summarised using a framework matrix method. DISCUSSION: The results of this study will inform the development and implementation of a context-specific strategy to enhance influenza vaccination rates among Bangladeshi HCWs. TRIAL REGISTRATION: Clinicaltrials.gov NCT05521763. Version 2.0 was registered in September 2022, and the first participant enrolled in March 2022. Retrospectively registered.

Theta power and theta-gamma coupling support long-term spatial memory retrieval.

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations to support long-term memory. Here we asked 10 presurgical epilepsy patients undergoing intracranial EEG recording to perform a long-term spatial memory task in desktop virtual reality and found that increased theta power in two discrete bands ("low" 2-5 Hz and "high" 6-11 Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between "low" theta phase and gamma amplitude during the same period was associated with improved task performance. Finally, low and high gamma amplitude appeared to peak at different phases of the theta cycle; providing a novel connection between human hippocampal function and rodent data. These results help to elucidate the role of theta oscillations and theta-gamma phase-amplitude coupling in human long-term memory.

Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data.

OBJECTIVE: To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans. METHODS: We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI-visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG. RESULTS: Seizure-onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG. SIGNIFICANCE: Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co-located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.

In-hospital and 30-day major adverse cardiac events in patients referred for ST-segment elevation myocardial infarction in Dhaka, Bangladesh.

BACKGROUND: There is a paucity of data regarding acute phase (in-hospital and 30-day) major adverse cardiac events (MACE) following ST-segment elevation myocardial infarction (STEMI) in Bangladesh. This study aimed to document MACE during the acute phase post-STEMI to provide information. METHODS: We enrolled STEMI patients of the National Institute of Cardiovascular Disease, Dhaka, Bangladesh, from August 2017 to October 2018 and followed up through 30 days post-discharge for MACE, defined as the composite of all-cause death, myocardial infarction, and coronary revascularization. Demographic information, cardiovascular risk factors, and clinical data were registered in a case report form. The Cox proportional hazard model was used for univariate and multivariate analysis to identify potential risk factors for MACE. RESULTS: A total of 601 patients, mean age 51.6 ± 10.3 years, 93% male, were enrolled. The mean duration of hospital stay was 3.8 ± 2.4 days. We found 37 patients (6.2%) to experience an in-hospital event, and 45 (7.5%) events occurred within the 30 days post-discharge. In univariate analysis, a significantly increased risk of developing 30-day MACE was observed in patients with more than 12 years of formal education, diabetes mellitus, or a previous diagnosis of heart failure. In a multivariate analysis, the risk of developing 30-day MACE was increased in patients with heart failure (hazard ratio = 4.65; 95% CI 1.64-13.23). CONCLUSIONS: A high risk of in-hospital and 30-day MACE in patients with STEMI exists in Bangladesh. Additional resources should be allocated providing guideline-recommended treatment for patients with myocardial infarction in Bangladesh.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Localisation in focal epilepsy: a practical guide.

The semiology of epileptic seizures reflects activation, or dysfunction, of areas of brain (often termed the symptomatogenic zone) as a seizure begins and evolves. Specific semiologies in focal epilepsies provide an insight into the location of the seizure onset zone, which is particularly important for presurgical epilepsy assessment. The correct diagnosis of paroxysmal events also depends on the clinician being familiar with the spectrum of semiologies. Here, we summarise the current literature on localisation in focal epilepsies using illustrative cases and discussing possible pitfalls in localisation.

Clinical and laboratory predictors of 30-day mortality in severe acute malnourished children with severe pneumonia.

OBJECTIVE: To determine the predictors of mortality within 30 days of hospital admission in a diarrhoeal disease hospital in Bangladesh. METHODS: Cohort study of hospitalised children aged 0-59 months with severe acute malnutrition (SAM) and severe pneumonia in Dhaka Hospital, icddr,b, Bangladesh from April 2015 to March 2017. Those discharged were followed up, and survival status at 30 days from admission was determined. Children who died were compared with the survivors in terms of clinical and laboratory biomarkers. Multivariable logistic regression analysis was used for calculating adjusted odds ratio for death within 30 days of hospital admission. RESULTS: We enrolled 191 children. Mortality within 30 days of admission was 6% (14/191). After adjusting for potential confounders (hypoxia, CRP and haematocrit) in logistic regression analysis, independent factors associated with death were female sex (aOR = 5.80, 95% CI: 1.34-25.19), LAZ <-4 (aOR = 6.51, 95% CI: 1.49-28.44) and Polymorphonuclear Leucocytes (PMNL) (>6.0 × 109 /L) (aOR = 1.06, 95% CI: 1.01-1.11). Using sex, Z-score for length for age (LAZ), and PMNL percentage, we used random forest and linear regression models to achieve a cross-validated AUC of 0.83 (95% CI: 0.82, 0.84) for prediction of 30-day mortality. CONCLUSIONS: The results of our data suggest that female sex, severe malnutrition (<-4 LAZ) and higher PMNL percentage were prone to be associated with 30-day mortality in children with severe pneumonia. Association of these factors may be used in clinical decision support for prompt identification and appropriate management for prevention of mortality in this population.

OBJECTIF: Déterminer les prédicteurs de mortalité dans les 30 jours suivant l'admission à l'hôpital dans un hôpital pour maladies diarrhéiques au Bangladesh. MÉTHODES: Etude de cohorte d'enfants hospitalisés âgés de 0 à 59 mois atteints de malnutrition aiguë sévère (MAS) et de pneumonie sévère à l'hôpital de Dhaka, icddr,b, au Bangladesh d'avril 2015 à mars 2017. Ceux qui ont été libérés ont été suivis et leur état de survie à 30 jours de l'admission a été déterminé. Les enfants décédés ont été comparés aux survivants en termes de biomarqueurs cliniques et de laboratoire. Une analyse de régression logistique multivariée a été utilisée pour calculer le rapport de cotes ajusté pour le décès dans les 30 jours suivant l'admission à l'hôpital. RÉSULTATS: Nous avons inscrit 191 enfants. La mortalité dans les 30 jours suivant l'admission était de 6% (14/191). Après ajustement pour les facteurs confusionnels potentiels (hypoxie, CRP et hématocrite) dans l'analyse de régression logistique, les facteurs indépendants associés au décès étaient le sexe féminin (aOR = 5,80 ; IC95%: 1,34 à 25,19), LAZ <-4 (aOR = 6,51 ; IC95%: 1,49-28,44) et leucocytes polymorphonucléaires (LPMN) (>6,0 x 109 /L) (aOR = 1,06 ; IC95%: 1,01-1,11). En utilisant le sexe, le score Z de la taille pour l'âge (LAZ) et le pourcentage de LPMN, nous avons utilisé des modèles de régression linéaire et de forest aléatoires pour obtenir une AUC validée croisée de 0,83 (IC95%: 0,82-0,84) pour la prédiction de la mortalité à 30 jours. CONCLUSIONS: Les résultats de nos données suggèrent que le sexe féminin, la malnutrition sévère (LAZ <-4) et un pourcentage plus élevé de LPMN étaient susceptibles d'être associés à la mortalité à 30 jours chez les enfants atteints de pneumonie sévère. L'association de ces facteurs peut être utilisée dans l'aide à la décision clinique pour une identification rapide et une prise en charge appropriée pour la prévention de la mortalité dans cette population.