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Purpose: This Hydrocephalus Clinical Research Network (HCRN) study had two aims: (1) to compare the predictive performance of the original ETV Success Score (ETVSS) using logistic regression modeling with other newer machine learning models and (2) to assess whether inclusion of imaging variables improves prediction performance using machine learning models. Methods: We identified children undergoing first-time ETV for hydrocephalus that were enrolled prospectively at HCRN sites between 200 and 2020. The primary outcome was ETV success 6 months after index surgery. The cohort was randomly divided into training (70%) and testing (30%) datasets. The classic ETVSS variables were used for logistic regression and machine learning models. Predictive performance of each model was evaluated on the testing dataset using area under the receiver operating characteristic curve (AUROC). Results: There were 752 patients that underwent first time ETV, of which 185 patients (24.6%) experienced ETV failure within 6 months. For aim 1, using the classic ETVSS variables, machine learning models did not outperform logistic regression with AUROC 0.60 (95% CI: 0.52–0.69) for Naïve Bayes (highest machine learning model performance) and 0.68 (95% CI: 0.60–0.76) for logistic regression. After inclusion of imaging features (aim 2), machine learning model prediction improved but remained no better than the above logistic regression with the highest AUROC of 0.67 (95% CI: 0.59–0.75) attained using Naïve Bayes architecture compared to 0.68 (95% CI: 0.59–0.76) for logistic regression. Conclusions: This contemporary multicenter observational cohort study demonstrated that machine learning modeling strategies did not improve performance of the ETVSS model over logistic regression. [ABSTRACT FROM AUTHOR]

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on aerobic and anaerobic media. The detection and identification of bacteria was done with high throughput DNA sequencing methods and mass spectrometry. The presence of bacteria was confirmed in 4 infection samples, of which 2 were after initial placement and 2 after revision surgery. Taxonomic identification was consistent with clinical microbiology laboratory results. Bacteria were not detected in any of the CSF samples collected at the time of the previous surgical events. While our findings do not provide direct evidence for long-term persistence of pathogens, they suggest the need for consideration of additional source material, such as biofilm and environmental swabs, and/or the use of more sensitive and specific analytical methods. [ABSTRACT FROM AUTHOR]

Objective: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention. Study design: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at –70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in STGG or standard clinical) were further analyzed using whole-genome amplification sequencing (WGAS). Results: 11/66 (17%) samples stored in STGG and 1/36 (3%) that underwent standard clinical microbiological culture demonstrated bacterial growth. Of the organisms present, 8 were common skin flora and 4 were potential pathogens; only 1 was also qPCR positive. WGAS findings and STGG culture findings were concordant for only 1 sample, identifying Staphylococcus epidermidis. No significant difference in time to second surgical intervention was observed between the STGG culture-positive and negative groups. Conclusion(s): Using high sensitivity methods, we detected the presence of bacteria in a subset of CSF samples at the time of first surgery. Therefore, the true presence of bacteria in CSF of children with hydrocephalus cannot be ruled out, though our findings may suggest these bacteria are contaminants or false positives of the detection methods. Regardless of origin, the detection of microbiota in the CSF of these children may not have any clinical significance. [ABSTRACT FROM AUTHOR]

One may question the moral or ethical right to continue with casual or unplanned new surgical procedures--procedures which may encompass no more than a placebo effect--when these procedures are costly [...]

We discuss research ethics challenges experienced while running a discrete choice experiment administered to caregivers of children with treatment resistant pediatric epilepsy. We highlight ethical considerations around the study design of the discrete choice experimental paradigm that pertain to vulnerability of and caregiving burden on the population, imbalance of benefit-to-load of participation, and limitations of cultural meaningfulness and generalizability. [ABSTRACT FROM AUTHOR]

Objective: Novel and minimally invasive neurotechnologies offer the potential to reduce the burden of epilepsy while avoiding the risks of conventional resective surgery. Few neurotechnologies have been tested in randomized controlled trials with pediatric populations, leaving clinicians to face decisions about whether to recommend these treatments with insufficient evidence about the relevant risks and benefits. This study specifically explores the preferences of clinicians for treating pediatric drug‐resistant epilepsy (DRE) with novel neurotechnologies. Methods: A discrete‐choice experiment (DCE) was designed to elicit the preferences of clinicians with experience in treating children with DRE using novel neurotechnological interventions. The preferences for six key attributes used when making treatment decisions (chances of clinically significant improvement in seizures, major and minor risks from intervention, availability of evidence, financial burden for the family, and access to the intervention) were estimated using a conditional logit model. The estimates from this model were then used to predict the adoption of existing novel neurotechnological interventions. Results: Sixty‐eight clinicians completed the survey: 33 neurosurgeons, 28 neurologists, and 7 other clinicians. Most clinicians were working in the United States (74%), and the remainder (26%) in Canada. All attributes, apart from the nearest location with access to the intervention, influenced preferences significantly. The chance of clinically significant improvement in seizures was the most positive influence on clinician preferences, but low‐quality evidence and a higher risk of major complications could offset these preferences. Of the existing neurotechnological interventions, vagus nerve stimulation was predicted to have the highest likelihood of adoption; deep brain stimulation had the lowest likelihood of adoption. Significance: The preferences of clinicians are drive primarily by the likelihood of achieving seizure freedom for their patients, but preferences for an intervention are largely eradicated if only low quality of evidence supporting the intervention is available. Until better evidence supporting the use of potentially effective, novel neurotechnologies becomes available, clinicians are likely to prefer more established treatments. [ABSTRACT FROM AUTHOR]

Globalization and the National Security State by Norrin M. Ripsman and T.V. Paul. New York, Oxford University Press, 2010. 296pp. $27.95. This book assesses the security consequences of globalization in [...]

This qualitative study investigated factors that guide caregiver decision making and ethical trade-offs for advanced neurotechnologies used to treat children with drug-resistant epilepsy. Caregivers with affected children were recruited to semi-structured focus groups or interviews at one of 4 major epilepsy centers in Eastern and Western Canada and the USA (n = 22). Discussions were transcribed and qualitative analytic methods applied to examine values and priorities (eg, risks, benefits, adherence, invasiveness, reversibility) of caregivers pertaining to novel technologies to treat drug-resistant epilepsy. Discussions revealed 3 major thematic branches for decision making: (1) features of the intervention—risks and benefits, with an emphasis on an aversion to perceived invasiveness; (2) decision drivers—trust in the clinical team, treatment costs; and (3) quality of available information about neurotechnological options. Overall, caregivers' definition of treatment success is more expansive than seizure freedom. The full involvement of their values and priorities must be considered in the decision-making process. [ABSTRACT FROM AUTHOR]

Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA V4 region (16S). Taxonomic assignments of sequences from WGA and 16S were compared with one another and with conventional microbiological cultures. While classification of bacteria was consistent among the 3 approaches, WGA provided additional insights into sample microbiological composition, such as showing relative abundances of microbial versus human DNA, identifying samples of questionable quality, and detecting significant viral load in some samples. One sample yielded sufficient non-human reads to allow assembly of a high-quality Staphylococcus epidermidis genome, denoted CLIMB1, which we characterized in terms of its MLST profile, gene complement (including putative antimicrobial resistance genes), and similarity to other annotated S. epidermidis genomes. Our results demonstrate that WGA directly applied to CSF is a valuable tool for the identification and genomic characterization of dominant microorganisms in CSF shunt infections, which can facilitate molecular approaches for the development of better diagnostic and treatment methods. [ABSTRACT FROM AUTHOR]

In case 1, we hypothesise that the cephalohaematoma developed into subgaleal abscess with bacterial seeding from the antecedent urinary tract infection. The blood culture was also negative, white cell count (WCC) was 5.7 × 10 SP 9 sp /L and C-reactive protein (CRP) was 77.4 mg/L. Cranial ultrasound showed a lentiform 8.9 × 6.9 cm collection consistent with a large uncomplicated cephalohaematoma. If the cephalohaematoma does show signs of localised infection with possible extension, appropriate imaging with high diagnostic yield for osteomyelitis (CT or magnetic resonance imaging) is warranted with consideration given to debridement. [Extracted from the article]

This qualitative study investigated factors that guide physicians' choices for minimally invasive and neuromodulatory interventions as alternatives to conventional surgery or medical management for pediatric drug-resistant epilepsy. North American physicians were recruited to one of 4 focus groups at national conferences. Discussions were analyzed using qualitative content analysis. A pragmatic neuroethics framework was applied to interpret results. Discussions revealed 2 major thematic branches: (1) clinical decision making and (2) ethical considerations. Under clinical decision making, physicians emphasized scientific evidence and patient candidacy when assessing neurotechnologies for patients. Ongoing seizures without intervention was important for safety and neurodevelopment. Under ethical considerations, resource allocation, among other financial considerations for technology adoption, were considerable sources of pressure on decision making. Access to neurotechnology was a salient theme differentiating Canadian and American contexts. When assessing novel neurotechnological interventions for pediatric drug-resistant epilepsy, physicians balance clinical and ethical factors to guide decision making and best practice. [ABSTRACT FROM AUTHOR]

Background: Epilepsy affects over 500,000 children in North America of whom 30% have drug-resistant epilepsy. Advancements with neurotechnologies show promising benefits, but the perceptions of these procedures by youth is unknown. Methods: We conducted semistructured interviews with 10 youth in British Columbia, Canada who underwent procedures for drug-resistant epilepsy involving different forms of neurotechnology (subdural grids, vagus nerve stimulation, responsive neurostimulation). Interviews were analyzed using the constant comparative qualitative method. Results: Four major thematic categories emerged from the interviews. Treatment values, impact of the disorder, personal context, and impact of neurotechnology. Conclusions: Besides the predictable goal of seizure reduction, a desire for autonomy and the importance of trust in the medical team emerged as dominant values within the 4 thematic categories that were explicit to the use of new neurotechnologies for the management of drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law (what should be regulated), what types of regulations are required (eligibility criteria, approval procedures, data collection, and oversight mechanisms), and how to approach international harmonization given the potential migration of researchers and patients. [ABSTRACT FROM AUTHOR]

Background: Nearly 20% of patients with cerebrospinal fluid (CSF) shunt infection develop reinfection. It is unclear whether reinfections are caused by an organism previously present or are independent infection events. Objective: We used bacterial culture and high throughput sequencing (HTS) of 16S ribosomal RNA (rRNA) genes to identify bacteria present in serial CSF samples obtained from children who failed CSF shunt infection treatment. We hypothesized that organisms that persist in CSF despite treatment would be detected upon reinfection. Design/methods: Serial CSF samples were obtained from 6 patients, 5 with 2 infections and 1 with 3 infections; the study was limited to those for which CSF samples were available from the end of infection and beginning of reinfection. Amplicons of the 16S rRNA gene V4 region were sequenced. Taxonomic assignments of V4 sequences were compared with bacterial species identified in culture. Results: Seven infection dyads averaging 13.5 samples per infection were analyzed. A median of 8 taxa [interquartile range (IQR) 5–10] were observed in the first samples from reinfection using HTS. Conventional culture correlated with high abundance of an organism by HTS in all but 1 infection. In 6 of 7 infection dyads, organisms identified by culture at reinfection were detected by HTS of culture-negative samples at the end of the previous infection. The median Chao-Jaccard abundance-based similarity index for matched infection pairs at end of infection and beginning of reinfection was 0.57 (IQR 0.07–0.87) compared to that for unmatched pairs of 0.40 (IQR 0.10–0.60) [p = 0.46]. Conclusion(s): HTS results were generally consistent with culture-based methods in CSF shunt infection and reinfection, and may detect organisms missed by culture at the end of infection treatment but detected by culture at reinfection. However, the CSF microbiota did not correlate more closely within patients at the end of infection and beginning of reinfection than between any two unrelated infections. We cannot reject the hypothesis that sequential infections were independent. [ABSTRACT FROM AUTHOR]

Objective: To characterize the clinical research landscape of pediatric drug-resistant epilepsy (DRE) with a focus on neurotechnology. Method: We searched the ClinicalTrials.gov registry using the terms "epilepsy" and "drug resistant" for studies including participants age 0-17 years. Returns were grouped by intervention (eg, neurotechnological, drug). Key trial features such as age range, trial status and outcomes were compared across interventions. Results: We identified 101 registered trials with pediatric DRE patients. Thirty-two (32%) investigate neurotechnological interventions, devices, or diagnostic procedures; 13 (41%) are currently active. Among neurotechnology trials, 15 (46%) investigate vagus nerve stimulation, transcranial direct current stimulation, or deep brain stimulation; few are specific to children. Of the remaining 69 trials, 37 investigate a drug, 17 investigate a dietary therapy, and 15 investigate another intervention. Seizure frequency is the most frequent primary outcome measured in the trials identified. Significance: The landscape of registered trials pertaining to pediatric DRE reflects a lag between clinical research and clinical practice, and highlights the need for timely evidence before novel neurotechnological interventions are widely adopted into clinical practice. [ABSTRACT FROM AUTHOR]