Approach, complications, and outcomes for 37 consecutive pediatric patients undergoing laser ablation for medically refractory epilepsy at Stanford Children's Health.

OBJECTIVE: The objective of this study was to better understand the safety and efficacy of laser interstitial thermal therapy (LITT) for children with medically refractory epilepsy. METHODS: Thirty-seven consecutive pediatric epilepsy patients at a single pediatric center who underwent LITT ablation of epileptogenic foci between May 2017 and December 2021 were retrospectively reviewed. Patient demographics, medication use, seizure frequency, prior surgical interventions, procedural details, and pre- and postoperative seizure history were analyzed. RESULTS: Thirty-seven pediatric patients (24 male, 13 female) with severe medically refractory epilepsy were included; all underwent stereo-electroencephalography (SEEG) prior to LITT. The SEEG electrode placement was based on the preoperative workup and tailored to each patient by the epileptologist and neurosurgeons working together to identify the epileptic network and hopefully quiet borders. Seizure onset was at a mean age of 2.70 ± 2.82 years (range 0.25-12 years), and the mean age at the time of LITT was 9.46 ± 5.08 years (range 2.41-17.86 years). Epilepsy was lesional in 23 patients (18 tuberous sclerosis, 4 focal cortical dysplasia, 1 gliosis) and nonlesional in 14. Eighteen patients had prior surgical interventions including open resections (n = 13: 11 single and 2 multiple), LITT (n = 4), or both (n = 1). LITT targeted a region adjacent to the previous target in 5 cases. The median number of lasers placed during the procedure was 3 (range 1-5). Complications occurred in 14 (37.8%) cases, only 3 (8.11%) of which resulted in a permanent deficit: 1 venous hemorrhage requiring evacuation following laser ablation, 1 aseptic meningitis, 2 immediate postoperative seizures, and 10 neurological deficits (7 transient and 3 permanent). Postoperatively, 22 (59.5%) patients were seizure free at the last follow-up (median follow-up 18.35 months, range 7.40-48.76 months), and the median modified Engel class was I (Engel class I in 22 patients, Engel class II in 2, Engel class III in 2, and Engel class IV in 11). Patients having tried a greater number of antiseizure medications before LITT were less likely to achieve seizure improvement (p = 0.046) or freedom (p = 0.017). Seizure improvement following LITT was associated with a shorter duration of epilepsy prior to LITT (p = 0.044), although postoperative seizure freedom was not associated with a shorter epilepsy duration (p = 0.667). Caregivers reported postoperative neurocognitive improvement in 17 (45.9%) patients. CONCLUSIONS: In this large single-institution cohort of pediatric patients with medically refractory seizures due to various etiologies, LITT was a relatively safe and effective surgical approach for seizure reduction and seizure freedom at 1 year of follow-up.

Ellagic acid-loaded, tween 80-coated, chitosan nanoparticles as a promising therapeutic approach against breast cancer: In-vitro and in-vivo study.

AIMS: Among polyphenolic phytoconstituents with anticancer properties, Ellagic acid (EA) is widely reported for its translational potential in vitro but efficient in vivo delivery of EA has been a challenge. We, for the first time, used a tween 80 coated nano delivery of Ellagic acid to evaluate its preclinical efficacy in vitro and in vivo for breast cancer. MAIN METHODS: To overcome the challenges of in vivo delivery, two batches of chitosan-based nanoformulations of EA (with and without tween 80 coating) were prepared by the ionotropic gelation method. The nanoformulations were characterized and further evaluated in vitro against breast cancer cells (MCF7) and in vivo with EAC tumor-bearing mice for establishing their anticancer efficacy compared to Ellagic acid alone. A quantitative simulation study was undertaken to understand if the observed antitumor efficacy is due to the synergistic efficacy of the Chitosan-Ellagic acid combination. KEY FINDINGS: Results revealed that nanoformulations consist of good nano-sized encapsulation of EA and showed good drug entrapment-release capacity. Nano-encapsulated EA is biocompatible and exhibited higher cytotoxicity in vitro compared to EA alone. Similarly, significantly higher tumor regression was observed in nano-EA treated mice compared to EA alone, and best efficacy was observed with the nanoformulation with tween 80 coating. Furthermore, nanoformulations showed higher apoptosis in tumor tissues with no significant tissue toxicity in vital organs. SIGNIFICANCE: We report synergism of Chitosan-Ellagic acid combination in the tween 80 coated nanoparticles of Ellagic acid resulting in enhanced anti-breast tumor efficacy that may be of translational value for other tumor types, too.

Relationship Between Statin-associated Muscle Symptoms, Serum Vitamin D and Low-density Lipoprotein Cholesterol - A Cross-sectional Study.

INTRODUCTION: Statin-associated muscle symptoms (SAMS) can lead to medication non-adherence among statin users. There is a complex relationship between SAMS, vitamin D and low-density lipoprotein cholesterol (LDL-C). The objective of this study was to evaluate the relationship between vitamin D, LDL-C and occurrence of SAMS. METHODS: This was a cross-sectional study in patients using statins. Thorough patient histories were taken, a clinical examination was conducted and SAMS were recorded. Levels of vitamin D, creatine phosphokinase (CPK) and LDL-C were measured. These parameters were compared amongst statin users with SAMS and those without SAMS. Levels of vitamin D and LDL-C were converted into percentiles and their relationship with SAMS was evaluated in terms of odds ratio. Receiver operating characteristics (ROC) were drawn, taking vitamin D and LDL-C as predictors of SAMS. RESULTS: A total of 121 statin users were enrolled in this study. Thirty-eight patients (31.4%) presented with SAMS. Significantly lower levels of serum vitamin D were observed amongst statin users with SAMS compared with those without SAMS (19.8 ± 9.67 ng/mL versus 25.0 ± 14.6 ng/mL; 95% confidence interval -10.4 to -0.07; p=0.04). With vitamin D levels less than or equal to 5th, 10th and 25th percentile, the chances of occurrence of SAMS were significantly higher, but not at the 50th percentile (corresponding vitamin D level of 20.21 ng/mL). LDL-C did not show any conclusive relationship with SAMS. ROC curves showed a significant discrimination for vitamin D levels, but not for LDL-C. CONCLUSION: Statin users with low levels of vitamin D are at increased risk of developing SAMS. However, LDL-C status of statin users failed to predict any meaningful association with SAMS. Given the small sample size of this study, these results should be regarded as preliminary.

Long-term incidence of glioma in Olmsted County, Minnesota, and disparities in postglioma survival rate: a population-based study.

BACKGROUND: We assessed glioma incidence and disparities in postglioma survival rate in the Olmsted County, Minnesota, population. METHODS: This population-based study assessed the incidence of pathologically confirmed primary gliomas between January 1, 1995, and December 31, 2014. Age- and sex-adjusted incidence rates per 100 000 person-years were calculated and standardized to the US white 2010 population. We compared incidence trends of glioma during our study period with previously published Olmsted County data from 1950 to 1990. We assessed postglioma survival rates among individuals with different socioeconomic status (SES), which was measured by a validated individual HOUsing-based SES index (HOUSES). RESULTS: We identified 135 incident glioma cases (93% white) with 20 pediatric (50% female) and 115 adult cases (44% female). Overall incidence rate during our study period, 5.51 per 100 000 person-years (95% CI: 4.56-6.46), showed no significant changes and was similar to that seen in 1950 to 1990, 5.5 per 100 000 person-years. The incidence of pediatric (age < 20 years) glioma was 2.49 (95% CI: 1.40-3.58), whereas adult glioma incidence was 6.47 (95% CI: 5.26-7.67). Among those with grade II to IV gliomas, individuals with lower SES (< median HOUSES) had significantly lower 5-year survival rates compared to those with higher SES, adjusted hazard ratio 1.61 (95% CI: 1.01-2.85). CONCLUSION: In a well-defined North American population, long-term glioma incidence appears stable since 1950. Significant socioeconomic disparities exist for postglioma survival.

Asthma and risk of glioma: a population-based case-control study.

OBJECTIVES: Literature suggests an inconsistent, but largely inverse, association between asthma and risk of glioma, which is primarily due to methodological inconsistency in sampling frame and ascertainment of asthma. The objective of the study was to clarify the association between asthma and risk of glioma by minimising methodological biases (eg, recall and detection bias). DESIGN: A population-based case-control study. SETTING: General population in Olmsted County, Minnesota, USA. PARTICIPANTS: All eligible biopsy-proven incident glioma cases (1995-2014) and two sets of controls among residents matched to age and sex (first set: community controls without glioma; second set: MRI-negative controls from the same community). METHODS: The predetermined asthma criteria via medical record review were applied to ascertain asthma status of cases and controls. History of asthma prior to index date was compared between glioma cases and their matched controls using conditional logistic regression models. Propensity score for asthma status was adjusted for multivariate analysis. RESULTS: We enrolled 135 glioma cases (median age at index date: 53 years) and 270 controls. Of the cases, 21 had a history of asthma (16%), compared with 36 of MRI controls (27%) (OR (95% CI) 0.48 (0.26 to 0.91), p=0.03). With MRI controls, an inverse association between asthma and risk of glioma persisted after adjusting for the propensity score for asthma status, but did not reach statistical significance probably due to the lack of statistical power (OR (95% CI) 0.48 (0.21 to 1.09); p=0.08). Based on comparison of characteristics of controls and cases, community controls seem to be more susceptible to a detection bias. CONCLUSIONS: While differential detection might account for the association between asthma and risk of glioma, asthma may potentially pose a protective effect on risk of glioma. Our study results need to be replicated by a larger study.

Spatio-temporal comparison of pertussis outbreaks in Olmsted County, Minnesota, 2004-2005 and 2012: a population-based study.

OBJECTIVE: Two pertussis outbreaks occurred in Olmsted County, Minnesota, during 2004-2005 and 2012 (5-10 times higher than other years), with significantly higher incidence than for the State. We aimed to assess whether there were similar spatio-temporal patterns between the two outbreaks. SETTING: Olmsted County, Minnesota, USA PARTICIPANTS: We conducted a population-based retrospective cohort study of all Olmsted County residents during the 2004-2005 and 2012 outbreaks, including laboratory-positive pertussis cases. PRIMARY OUTCOME MEASURE: For each outbreak, we estimated (1) age-specific incidence rate using laboratory-positive pertussis cases (numerator) and the Rochester Epidemiology Project Census (denominator), a medical record-linkage system for virtually all Olmsted County residents, and (2) pertussis case density using kernel density estimation to identify areas with high case density. To account for population size, we calculated relative difference of observed density and expected density based on age-specific incidence. RESULTS: We identified 157 and 195 geocoded cases in 2004-2005 and 2012, respectively. Incidence was the highest among adolescents (ages 11 to <14 years) for both outbreaks (9.6 and 7.9 per 1000). The 2004-2005 pertussis outbreak had higher incidence in winter (52% of cases) versus summer in 2012 (53%). We identified a consistent area with higher incidence at the beginning (ie, first quartile) of two outbreaks, but it was inconsistent for later quartiles. The relative difference maps for the two outbreaks suggest a greater role of neighbourhood population size in 2012 compared with 2004-2005. CONCLUSIONS: Comparing spatio-temporal patterns between two pertussis outbreaks identified a consistent geographical area with higher incidence of pertussis at the beginning of outbreaks in this community. This finding can be tested in future outbreaks, and, if confirmed, can be used for identifying epidemiological risk factors clustered in such areas for geographically targeted intervention.

Prevalence of premenstrual dysphoric disorder among school-going adolescent girls.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome which has a significant negative impact on the various domains of life of adolescent girls. AIM: The aim of this study was to estimate the prevalence of PMDD in adolescent girls studying in classes 7th-10th and ascertain the level of stress, anxiety, and depression among them. METHODOLOGY: A cross-sectional study was conducted in three all-girls schools in Chandigarh (two - government and one - private) after taking necessary permissions. Participants were evaluated on a self-rated questionnaire which included the PMDD scale, Perceived Stress Scale, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Patient Health Questionnaire-9. RESULTS: A total of 397 girls participated in the study. The mean age of respondents was 14.34 (standard deviation [SD]: 1.17; range: 11-20) years, with most (44%) studying in class 10th. The mean age of attaining menarche was 12.54 (SD: 0.92; range: 10-15) years. The prevalence of PMDD was found to be 4.8% (n = 19). Majority of the respondents reported moderate levels of perceived stress (62%). A positive correlation was seen between the severity of PMDD, age, levels of perceived stress, severity of depression, and anxiety in the respondents. CONCLUSION: Nearly 5% of adolescent girls suffer from PMDD, with higher prevalence among those with depression, GAD, and higher perceived stress. Thus, there is a need to screen adolescent females for PMDD at the earliest and institute intervention to minimize its negative impact.

Automated chart review utilizing natural language processing algorithm for asthma predictive index.

BACKGROUND: Thus far, no algorithms have been developed to automatically extract patients who meet Asthma Predictive Index (API) criteria from the Electronic health records (EHR) yet. Our objective is to develop and validate a natural language processing (NLP) algorithm to identify patients that meet API criteria. METHODS: This is a cross-sectional study nested in a birth cohort study in Olmsted County, MN. Asthma status ascertained by manual chart review based on API criteria served as gold standard. NLP-API was developed on a training cohort (n = 87) and validated on a test cohort (n = 427). Criterion validity was measured by sensitivity, specificity, positive predictive value and negative predictive value of the NLP algorithm against manual chart review for asthma status. Construct validity was determined by associations of asthma status defined by NLP-API with known risk factors for asthma. RESULTS: Among the eligible 427 subjects of the test cohort, 48% were males and 74% were White. Median age was 5.3 years (interquartile range 3.6-6.8). 35 (8%) had a history of asthma by NLP-API vs. 36 (8%) by abstractor with 31 by both approaches. NLP-API predicted asthma status with sensitivity 86%, specificity 98%, positive predictive value 88%, negative predictive value 98%. Asthma status by both NLP and manual chart review were significantly associated with the known asthma risk factors, such as history of allergic rhinitis, eczema, family history of asthma, and maternal history of smoking during pregnancy (p value < 0.05). Maternal smoking [odds ratio: 4.4, 95% confidence interval 1.8-10.7] was associated with asthma status determined by NLP-API and abstractor, and the effect sizes were similar between the reviews with 4.4 vs 4.2 respectively. CONCLUSION: NLP-API was able to ascertain asthma status in children mining from EHR and has a potential to enhance asthma care and research through population management and large-scale studies when identifying children who meet API criteria.

PROPER: Development of an Early Pediatric Intensive Care Unit Readmission Risk Prediction Tool.

OBJECTIVE: No risk prediction model is currently available to measure patient's probability for readmission to the pediatric intensive care unit (PICU). This retrospective case-control study was designed to assess the applicability of an adult risk prediction score (Stability and Workload Index for Transfer [SWIFT]) and to create a pediatric version (PRediction Of PICU Early Readmissions [PROPER]). DESIGN: Eighty-six unplanned early (<48 hours) PICU readmissions from January 07, 2007, to June 30, 2014, were compared with 170 random controls. Patient- and disease-specific data and PICU workload factors were compared across the 2 groups. Factors statistically significant on multivariate analysis were included in the creation of the risk prediction model. The SWIFT scores were calculated for cases and controls and compared for validation. RESULTS: Readmitted patients were younger, weighed less, and were more likely to be admitted from the emergency department. There were no differences in gender, race, or admission Pediatric Index of Mortality scores. A higher proportion of patients in the readmission group had a Pediatric Cerebral Performance Category in the moderate to severe disability category. Cases and controls did not differ with respect to staff workload at discharge or discharge day of the week; there was a much higher proportion of patients on supplemental oxygen in the readmission group. Only 2 of 5 categories in the SWIFT model were significantly different, and although the median SWIFT score was significantly higher in the readmissions group, the model discriminated poorly between cases and controls (area under the curve: 0.613). A 7-category PROPER score was created based on a multiple logistic regression model. Sensitivity of this model (score ≥12) for the detection of readmission was 81% with a positive predictive value of 0.50. CONCLUSION: We have created a preliminary model for predicting patients at risk of early readmissions to the PICU from the hospital floor. The SWIFT score is not applicable for predicting the risk for pediatric population.

Design and α-testing of an electronic rounding tool (CERTAINp) to improve process of care in pediatric intensive care unit.

Increasing process complexity in the pediatric intensive care unit (PICU) can lead to information overload resulting in missing pertinent information and potential errors during morning rounds. An efficient model using a novel electronic rounding tool was designed as part of a broader critical care decision support system-checklist for early recognition and treatment of acute illness and injury in pediatrics (CERTAINp). We aimed to evaluate its impact on improving the process of care during rounding. Prospective pre- and post-interventional data included: team performance baseline assessment, patient safety discussion, guideline adherence, rounding time, and a survey of Residents' and Nurses' perception using a Likert scale. Attending physicians were blinded to the components of the assessment. A total of 113 pre-intervention and 114 post-intervention roundings were recorded by direct observation. Pre-intervention (108) and post-intervention staff surveys (80) were obtained. Adherence to standard of care guidelines improved to >97 % in all data points, with maximum increase seen in discussions of ulcer prophylaxis, bowel protocol, DVT prophylaxis, skin care, glucose control and head of bed elevation (2-28 % pre-vs. 100 % for all post-intervention, p < 0.01). Significant improvement was noticed in spontaneous breathing trials, sedation breaks and need for devices (45-57 % pre- vs. 100 % for all post-intervention, p < 0.01). Rounding time (mean ± SD) increased by 2 min/patient (8.0 ± 5.8 min pre-intervention vs. 9.9 ± 5.7 min post-intervention, p = 0.002). Staff reported improved perception of all aspects of rounding. Utilization of the CERTAINp rounding tool led to perfect compliance to the discussion of best practice guidelines; had minimal impact on rounding time and improved PICU staff satisfaction.

Comparison of staff and family perceptions of causes of noise pollution in the Pediatric Intensive Care Unit and suggested intervention strategies.

Noise and excessive, unwanted sound in the Pediatric Intensive Care Unit (PICU) is common and has a major impact on patients' sleep and recovery. Previous research has focused mostly on absolute noise levels or included only staff as respondents to acknowledge the causes of noise and to plan for its reduction. Thus far, the suggested interventions have not ameliorated noise, and it continues to serve as a barrier to recovery. In addition to surveying PICU providers through internet-based software, patients' families were evaluated through in-person interviews utilizing a pretested instrument over 3 months. Families of patients admitted for more than 24 h were considered eligible for evaluation. Participants were asked to rank causes of noise from 1 to 8, with eight being highest, and identified potential interventions as effective or ineffective. In total, 50 families from 251 admissions and 65 staff completed the survey. Medical alarms were rated highest (mean ± standard deviation [SD], 4.9 ± 2.1 [2.8-7.0]), followed by noise from medical equipment (mean ± SD, 4.7 ± 2.1 [2.5-6.8]). This response was consistent among PICU providers and families. Suggested interventions to reduce noise included keeping a patient's room door closed, considered effective by 93% of respondents (98% of staff; 88% of families), and designated quiet times, considered effective by 82% (80% of staff; 84% of families). Keeping the patient's door closed was the most effective strategy among survey respondents. Most families and staff considered medical alarms an important contributor to noise level. Because decreasing the volume of alarms such that it cannot be heard is inappropriate, alternative strategies to alert staff of changes in vital signs should be explored.

A survey on the resources and practices in pediatric critical care of resource-rich and resource-limited countries.

BACKGROUND: Contemporary critical care research necessitates involvement of multiple centers, preferably from many countries. Adult and pediatric research networks have produced outstanding data; however, their involvement is restricted to a small percentage of the industrialized nations. Implementation of their findings in low- and middle-income countries (LMICs) is fraught with challenges. METHODS: We conducted an online international survey to assess and compare disease burden and resources to participate in multicenter research studies through a listserv of the World Federation of Pediatric Intensive and Critical Care Societies. Respondents were grouped into high-income countries and LMICs on the basis of World Bank classification. RESULTS: Survey was completed by 73 centers in 34 countries (34 from high-income countries and 39 from LMICs). Compared with high-income countries, the pediatric intensive care units in LMICs were characterized by a lower number of critical care specialists, more difficult access to hemodialysis, and a lower number of elective postoperative patients, but a similar overall disease burden. Training and resources for research were comparable in the two cohorts. CONCLUSIONS: Although differences exist in access to both trained providers and equipment, the survey results were more striking in their similarity. It is essential that centers from LMICs be included in multinational studies, to generate results applicable to all children worldwide.