Implementation of a critical care outreach team in a children's hospital.

Introduction: Proactive surveillance by a critical care outreach team (CCOT) can promote early recognition of deterioration in hospitalized patients but is uncommon in pediatric rapid response systems (RRSs). After our children's hospital introduced a CCOT in 2019, we aimed to characterize early implementation outcomes. We hypothesized that CCOT rounding would identify additional children at risk for deterioration. Methods: The CCOT, staffed by a dedicated critical care nurse (RN), respiratory therapist, and attending, conducts daily in-person rounds with charge RNs on medical-surgical units, to screen RRS-identified high-risk patients for deterioration. In this prospective study, observers tracked rounds discussion content, participation, and identification of new high-risk patients. We compared 'identified-patient-discussions' (IPD) about RRS-identified patients, and 'new-patient-discussions' (NPD) about new patients with Fisher's exact test. For new patients, we performed thematic analysis of clinical data to identify deterioration related themes. Results: During 348 unit-rounds over 20 days, we observed 383 discussions - 35 (9%) were NPD. Frequent topics were screening for clinical concerns (374/383, 98%), active clinical concerns (147/383, 39%), and watcher activation (66/383, 17%). Most discussions only included standard participants (353/383, 92%). Compared to IPD, NPD more often addressed active concerns (74.3% vs 34.8%, p < 0.01) and staffing resource concerns (5.7% vs 0.6%, p < 0.04), and more often incorporated extra participants (25.7% vs 6%, p < 0.01). In thematic analysis of 33 new patients, most (29/33, 88%) had features of deterioration. Conclusion: A successfully implemented CCOT enhanced identification of clinical deterioration not captured by existing RRS resources. Future work will investigate its impact on operational safety and patient-centered outcomes.

Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BACKGROUND: Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis. METHODS: Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods. RESULTS: Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling. CONCLUSIONS: Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.

Landscape of genetic infantile epileptic spasms syndrome-A multicenter cohort of 124 children from India.

OBJECTIVE: Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce in developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children. METHODS: Between January 2021 and June 2022, this cross-sectional study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural-genetic and structural-metabolic etiology, were recruited and underwent detailed in-person assessment for phenotypic characterization. The multicentric data on the genotypic and phenotypic characteristics of genetic IESS were collated and analyzed. RESULTS: Of 124 probands (60% boys, history of consanguinity in 15%) with genetic IESS, 105 had single gene disorders (104 nuclear and one mitochondrial), including one with concurrent triple repeat disorder (fragile X syndrome), and 19 had chromosomal disorders. Of 105 single gene disorders, 51 individual genes (92 variants including 25 novel) were identified. Nearly 85% of children with monogenic nuclear disorders had autosomal inheritance (dominant-55.2%, recessive-14.2%), while the rest had X-linked inheritance. Underlying chromosomal disorders included trisomy 21 (n = 14), Xq28 duplication (n = 2), and others (n = 3). Trisomy 21 (n = 14), ALDH7A1 (n = 10), SCN2A (n = 7), CDKL5 (n = 6), ALG13 (n = 5), KCNQ2 (n = 4), STXBP1 (n = 4), SCN1A (n = 4), NTRK2 (n = 4), and WWOX (n = 4) were the dominant single gene causes of genetic IESS. The median age at the onset of epileptic spasms (ES) and establishment of genetic diagnosis was 5 and 12 months, respectively. Pre-existing developmental delay (94.3%), early age at onset of ES (<6 months; 86.2%), central hypotonia (81.4%), facial dysmorphism (70.1%), microcephaly (77.4%), movement disorders (45.9%) and autistic features (42.7%) were remarkable clinical findings. Seizures other than epileptic spasms were observed in 83 children (66.9%). Pre-existing epilepsy syndrome was identified in 21 (16.9%). Nearly 60% had an initial response to hormonal therapy. SIGNIFICANCE: Our study highlights a heterogenous genetic landscape and phenotypic pleiotropy in children with genetic IESS.

Opportunities to improve diagnosis in emergency transfers to the pediatric intensive care unit.

BACKGROUND: Late recognition of in-hospital deterioration is a source of preventable harm. Emergency transfers (ET), when hospitalized patients require intensive care unit (ICU) interventions within 1 h of ICU transfer, are a proximal measure of late recognition associated with increased mortality and length of stay (LOS). OBJECTIVE: To apply diagnostic process improvement frameworks to identify missed opportunities for improvement in diagnosis (MOID) in ETs and evaluate their association with outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: A single-center retrospective cohort study of ETs, January 2015 to June 2019. ET criteria include intubation, vasopressor initiation, or ≥ $\ge \phantom{\rule{}{0ex}}$ 60 mL/kg fluid resuscitation 1 h before to 1 h after ICU transfer. The primary exposure was the presence of MOID, determined using SaferDx. Cases were screened by an ICU and non-ICU physician. Final determinations were made by an interdisciplinary group. Diagnostic process improvement opportunities were identified. MAIN OUTCOME AND MEASURES: Primary outcomes were in-hospital mortality and posttransfer LOS, analyzed by multivariable regression adjusting for age, service, deterioration category, and pretransfer LOS. RESULTS: MOID was identified in 37 of 129 ETs (29%, 95% confidence interval [CI] 21%-37%). Cases with MOID differed in originating service, but not demographically. Recognizing the urgency of an identified condition was the most common diagnostic process opportunity. ET cases with MOID had higher odds of mortality (odds ratio 5.5; 95% CI 1.5-20.6; p = .01) and longer posttransfer LOS (rate ratio 1.7; 95% CI 1.1-2.6; p = .02). CONCLUSION: MOID are common in ETs and are associated with increased mortality risk and posttransfer LOS. Diagnostic improvement strategies should be leveraged to support earlier recognition of clinical deterioration.

Leveraging EHR Data to Evaluate the Association of Late Recognition of Deterioration With Outcomes.

OBJECTIVES: Emergency transfers (ETs), deterioration events with late recognition requiring ICU interventions within 1 hour of transfer, are associated with adverse outcomes. We leveraged electronic health record (EHR) data to assess the association between ETs and outcomes. We also evaluated the association between intervention timing (urgency) and outcomes. METHODS: We conducted a propensity-score-matched study of hospitalized children requiring ICU transfer between 2015 and 2019 at a single institution. The primary exposure was ET, automatically classified using Epic Clarity Data stored in our enterprise data warehouse endotracheal tube in lines/drains/airway flowsheet, vasopressor in medication administration record, and/or ≥60 ml/kg intravenous fluids in intake/output flowsheets recorded within 1 hour of transfer. Urgent intervention was defined as interventions within 12 hours of transfer. RESULTS: Of 2037 index transfers, 129 (6.3%) met ET criteria. In the propensity-score-matched cohort (127 ET, 374 matched controls), ET was associated with higher in-hospital mortality (13% vs 6.1%; odds ratio, 2.47; 95% confidence interval [95% CI], 1.24-4.9, P = .01), longer ICU length of stay (subdistribution hazard ratio of ICU discharge 0.74; 95% CI, 0.61-0.91, P < .01), and longer posttransfer length of stay (SHR of hospital discharge 0.71; 95% CI, 0.56-0.90, P < .01). Increased intervention urgency was associated with increased mortality risk: 4.1% no intervention, 6.4% urgent intervention, and 10% emergent intervention. CONCLUSIONS: An EHR measure of deterioration with late recognition is associated with increased mortality and length of stay. Mortality risk increased with intervention urgency. Leveraging EHR automation facilitates generalizability, multicenter collaboratives, and metric consistency.

A Quality Improvement Initiative to Improve Patient Safety Event Reporting by Residents.

INTRODUCTION: Residents play a key role in patient care at academic medical centers and have unique insights into safety improvement opportunities. At our institution, <1% of safety events were reported by resident trainees. The primary objective of this quality improvement (QI) initiative was to increase the monthly incidence of event reporting by pediatric residents by 20% from baseline within 12 months. METHODS: A QI team used the model for improvement to identify barriers to submitting safety event reports. The team used multiple intervention cycles to increase knowledge and promote engagement in event reporting. Interventions included educational tip sheets, a hospital-wide Morbidity and Mortality (M&M) conference, peer recognition and acknowledgment by senior leadership for report submission, and an interactive reporting activity. The outcome measure was monthly number of reports filed by residents. The process measure was the number of unique residents submitting a report each month. Time to complete a report was a balancing measure. RESULTS: The number of reports placed by residents increased significantly, with a centerline shift from 15 to 29 reports per month (statistical process control chart-Fig. 3). The number of unique residents submitting reports increased from 10 to 22 per month. The time to complete a report was unchanged. CONCLUSIONS: Engaging residents in patient safety initiatives through education, experiential learning, and recognition can increase safety event reporting by residents. Future planned interventions include enhancing safety event reporting technology, developing patient safety faculty and resident champions, and increasing transparency regarding outcomes of safety event reports.

A Resident-driven Initiative to Increase Bedside Teaching on Interdisciplinary Rounds.

Inpatient rounding serves numerous roles. The American Academy of Pediatrics recommends a family-centered bedside model. Residents identified physical examination teaching during and satisfaction with rounds as areas for improvement. A resident group developed a project utilizing quality improvement (QI) methodology to address these concerns. We aimed to increase the frequency of bedside physical examination teaching most or every day on a single inpatient unit by 20% over 1 year, with secondary goals to increase the percentage of interns spending one hour or more at bedside per day by 10% and intern satisfaction by 15%, without impacting rounding duration. METHODS: We developed an organizational structure to complete a long-term resident-led project. Interventions included daily bedside examination teaching on rounds, afternoon examinations, goal communication, topic recording, and a teaching "tip sheet." Using an institutional QI framework, we utilized iterative plan-do-study-act cycles to implement interventions and surveys to assess outcomes, with rounding efficiency as a balancing measure. RESULTS: The survey response rate was 57%. Bedside teaching frequency increased from a mean of 10% to 61%, perceived time at the bedside increased from 37% to 59%, and rounding satisfaction improved from a rating of 6.7/10 to 7.4/10. Efficiency was not impacted. CONCLUSIONS: We improved inpatient rounds bedside physical examination teaching and satisfaction without sacrificing efficiency. This project demonstrates the feasibility and success of a resident-driven education initiative to successfully motivate fellow residents and colleagues across disciplines to enact change. The organizational structure may serve as a model for resident-led QI projects across institutions.

Ventilator-Weaning Pathway Associated With Decreased Ventilator Days in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: There is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors. DESIGN: Secondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days. SETTING: Large academic tertiary-care PICU. PATIENTS: Children with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation. INTERVENTIONS: Implementation of a ventilator-weaning pathway on May 2016. MEASUREMENTS AND MAIN RESULTS: Of 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders. CONCLUSIONS: Ventilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.

Improving Disposition Decision-Making for Pediatric Diabetic Ketoacidosis: A Quality Improvement Study.

INTRODUCTION: In many centers, children with diabetic ketoacidosis (DKA) receive care either in an endocrinology ward or a pediatric intensive care unit (PICU). We conducted a quality improvement (QI) initiative to reduce potentially avoidable PICU admissions of children with DKA without increasing endocrinology ward-to-PICU transfers. METHODS: A survey of providers demonstrated opportunities to increase awareness of institutional criteria for PICU admissions of children with DKA. We created an electronic health record (EHR) dot-phrase, prepopulated with these criteria, and placed a note in the EHR for all patients with DKA as a reference for all providers. An EHR-based data report was created to monitor the disposition of DKA patients and the use of the dot-phrase (process measure). The primary outcome measure was the potentially avoidable PICU admissions for patients with DKA. Endocrinology ward-to-PICU transfers were tracked as a balancing measure to ensure safe disposition. RESULTS: After the implementation of the dot-phrase, use was variable, but averaged 33.4% over 1 year. The percentage of DKA admissions classified as potentially avoidable PICU stays decreased from 4.1% to 0.5%, with a concurrent decrease in the total percentage of PICU admissions for DKA from 19.1% to 8.4%. The percentage of endocrinology ward-to-PICU transfers also declined from 0.8% to 0%. CONCLUSIONS: A novel EHR-based intervention increasing awareness and documentation of established pediatric DKA management guidelines can be used to safely reduce PICU admissions for DKA without increasing the rate of endocrinology ward-to-intensive care unit transfers.

Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients.

BACKGROUND: Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively. Till date, nearly 76 mutations in PPT1 and approximately 140 mutations, including large deletion/duplications, in TPP1 genes have been reported in the literature. The present study includes 34 unrelated Indian patients (12 females and 22 males) having epilepsy, visual impairment, cerebral atrophy, and cerebellar atrophy. METHODS: The biochemical investigation involved measuring the palmitoyl protein thioesterase 1 and tripeptidy peptidase l enzyme activity from the leukocytes. Based on the biochemical analysis all patients were screened for variations in either PPT1 gene or TPP1 gene using bidirectional Sanger sequencing. In cases where Sanger sequencing results was uninformative Multiplex Ligation-dependent Probe Amplification technique was employed. The online tools performed the protein homology modeling and orthologous conservation of the novel variants. RESULTS: Out of 34 patients analyzed, the biochemical assay confirmed 12 patients with NCL1 and 22 patients with NCL2. Molecular analysis of PPT1 gene in NCL1 patients revealed three known mutations (p.Val181Met, p.Asn110Ser, and p.Trp186Ter) and four novel variants (p.Glu178Asnfs*13, p.Pro238Leu, p.Cys45Arg, and p.Val236Gly). In the case of NCL2 patients, the TPP1 gene analysis identified seven known mutations and eight novel variants. Overall these 15 variants comprised seven missense variants (p.Met345Leu, p.Arg339Trp, p.Arg339Gln, p.Arg206Cys, p.Asn286Ser, p.Arg152Ser, p.Tyr459Ser), four frameshift variants (p.Ser62Argfs*19, p.Ser153Profs*19, p.Phe230Serfs*28, p.Ile484Aspfs*7), three nonsense variants (p.Phe516*, p.Arg208*, p.Tyr157*) and one intronic variant (g.2023_2024insT). No large deletion/duplication was identified in three NCL1 patients where Sanger sequencing study was normal. CONCLUSION: The given study reports 34 patients with Batten disease. In addition, the study contributes four novel variants to the spectrum of PPT1 gene mutations and eight novel variants to the TPP1 gene mutation data. The novel pathogenic variant p.Pro238Leu occurred most commonly in the NCL1 cohort while the occurrence of a known pathogenic mutation p.Arg206Cys dominated in the NCL2 cohort. This study provides an insight into the molecular pathology of NCL1 and NCL2 disease for Indian origin patients.

Integrating Theory, Content, and Method to Foster Critical Consciousness in Medical Students: A Comprehensive Model for Cultural Competence Training.

Many efforts to design introductory "cultural competence" courses for medical students rely on an information delivery (competence) paradigm, which can exoticize patients while obscuring social context, medical culture, and power structures. Other approaches foster a general open-minded orientation, which can remain nebulous without clear grounding principles. Medical educators are increasingly recognizing the limitations of both approaches and calling for strategies that reenvision cultural competence training. Successfully realizing such alternative strategies requires the development of comprehensive models that specify and integrate theoretical frameworks, content, and teaching principles.In this article, the authors present one such model: Introduction to Medicine and Society (IMS), a required cultural competence course launched in 2013 for first-year medical students at the Perelman School of Medicine at the University of Pennsylvania. Building on critical pedagogy, IMS is centered on a novel specification of "critical consciousness" in clinical practice as an orientation to understanding and pragmatic action in three relational domains: internal, interpersonal, and structural. Instead of transmitting discrete "facts" about patient "types," IMS content provokes students to engage with complex questions bridging the three domains. Learning takes place in a small-group space specifically designed to spur transformation toward critical consciousness. After discussing the three key components of the course design and describing a representative session, the authors discuss the IMS model's implications, reception by students and faculty, and potential for expansion. Their early experience suggests the IMS model successfully engages students and prepares future physicians to critically examine experiences, manage interpersonal dynamics, and structurally contextualize patient encounters.

Clinical and molecular characterization of patients with gross hypotonia and impaired lower motor neuron function.

Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. The aim was to study the clinical and molecular characteristics of patients suspected with SMA. It was a cross sectional study of 105 cases from January 2008 to August 2012. Patients demographic and presenting features and PCR findings were noted. 65 (62%) cases had a confirmed diagnosis of SMA. Werdnig Hoffman disease (SMA type I) was the commonest variant seen in 34 (52.3%) children. Molecular analysis demonstrated deletion of both exon 7 and 8 of SMN1 gene in 83.1% of cases.

Peer-mediated multimodal intervention program for the treatment of children with ADHD in India: one-year followup.

The objective was to assess the efficacy of a one-year, peer-mediated interventional program consisting of yoga, meditation and play therapy maintained by student volunteers in a school in India. The population consisted of 69 students between the ages of 6 and 11 years, previously identified as having attention deficit hyperactivity disorder (ADHD). A program, known as Climb-Up, was initially embedded in the school twice weekly. Local high school student volunteers were then trained to continue to implement the program weekly over the period of one year. Improvements in ADHD symptoms and academic performance were assessed using Vanderbilt questionnaires completed by both parents and teachers. The performance impairment scores for ADHD students assessed by teachers improved by 6 weeks and were sustained through 12 months in 46 (85%) of the enrolled students. The improvements in their Vanderbilt scores assessed by parents were also seen in 92% (P < 0.0001, Wilcoxon). The Climb-Up program resulted in remarkable improvements in the students' school performances that were sustained throughout the year. These results show promise for a cost-effective program that could easily be implemented in any school.

Multimodal behavior program for ADHD incorporating yoga and implemented by high school volunteers: a pilot study.

A low-cost resource approach to ADHD therapy would be a practical approach to treating children in developing countries. Research has shown that ADHD is prevalent in all areas of the world, and yet treatment for children in more impoverished countries is still lacking. The approach taken was to combine yoga and meditation combined with multimodal behavioral therapy program for children ageing 6 to 11. The program was kept low cost by using trained high school volunteers and integrating the program within the public school. After 6 weeks of the program, 90.5% of children showed improvement as measured by their performance impairment score, a measurement of academic performance. Parent and Teacher evaluations of behavior also found improvement as 25 of the 64 children (39.1%) improved into the normal range as measured by the Vanderbilt questionnaire. Moreover, children could successfully learn both yoga and meditation from high school students irrespective of their age, ADHD type, or initial performance impairment. The results demonstrate efficacy of a multimodal behavioral program incorporating yoga and meditation. The use of high school volunteers from schools in the area demonstrates an effective low-cost and universally applicable approach.

Development of new adsorbent chitin for column preconcentration and spectrophotometric trace determination of Ziram and Zineb in synthetic, commercial samples and food-stuffs.

A procedure has been developed for the determination of zinc(II) bis(dimethyldithiocarbamate) (Ziram) or zinc(II) ethylenebisdithiocarbamate (Zineb) present in a large volume of aqueous solution after preconcentration on a column using chitin-1-(2'pyridylazo)-2-naphthol (PAN) as adsorbent. Ziram/Zineb are quantitatively retained on the column as Zn-PAN complex in the pH range 9.0-11.0 and at a flow rate of 1-8 ml/min. Complex adsorbed on chitin was eluted from the column with dimethylformamide (DMF) and absorbance of the eluate was measured at 550 nm against a reagent blank. Beer's law is obeyed over the concentration range 5.3-55.8 microg of Ziram and 6.8-49.0 microg of Zineb in 25 ml of the final DMF solution. Ten replicate determinations on a sample solution containing 45.22 microg of Ziram or 40.86 microg of Zineb gave a mean absorbance of 0.30 with a relative standard deviation 1.6 and 1.8%, respectively. The interference of various ions has been studied. Many alkali metals and metal salts do not interfere. The method has been employed to the determination of Ziram and Zineb in commercial samples and in various foodstuffs and the results were compared with the earlier reported methods.