The impact of nuance DAX ambient listening AI documentation: a cohort study.

OBJECTIVE: To assess the impact of the use of an ambient listening/digital scribing solution (Nuance Dragon Ambient eXperience (DAX)) on caregiver engagement, time spent on Electronic Health Record (EHR) including time after hours, productivity, attributed panel size for value-based care providers, documentation timeliness, and Current Procedural Terminology (CPT) submissions. MATERIALS AND METHODS: We performed a peer-matched controlled cohort study from March to September 2022 to evaluate the impact of DAX in outpatient clinics in an integrated healthcare system. Primary outcome measurements included provider engagement survey results, reported patient safety events related to DAX use, patients' Likelihood to Recommend score, number of patients opting out of ambient listening, change in work relative values units, attributed value-based primary care panel size, documentation completion and CPT code submission deficiency rates, and note turnaround time. RESULTS: A total of 99 providers representing 12 specialties enrolled in the study; 76 matched control group providers were included for analysis. Median utilization of DAX was 47% among active participants. We found positive trends in provider engagement, while non-participants saw worsening engagement and no practical change in productivity. There was a statistically significant worsening of after-hours EHR. There was no quantifiable effect on patient safety. DISCUSSION: Nuance DAX use showed positive trends in provider engagement at no risk to patient safety, experience, or clinical documentation. There were no significant benefits to patient experience, documentation, or measures of provider productivity. CONCLUSION: Our results highlight the potential of ambient dictation as a tool for improving the provider experience. Head-to-head comparisons of EHR documentation efficiency training are needed.

Agile Implementation of Innovative End to End Technical Solutions for Respiratory Testing in the COVID-19 Pandemic.

The COVID-19 pandemic required rapid implementation testing at large scale. We describe our approach to creating an efficient and highly scalable end-to-end testing and reporting workflow. We utilized a combination of consumer-driven workflows, a consistent ordering and data collection EMR user interface, an EMR independent entry point for affiliated providers, and rapidly evolving automation of screening, registration, patient identification, curbside specimen management, and prioritization logic. Our agile approach allowed us to transition from people-driven processes and gain efficiencies utilizing previously developed informatics infrastructure, new solutions and emerging consumer digital tools. We supported over 1,000,000 tests with >200 prioritization logic changes without requiring education or changing the provider ordering workflows, handled patient-driven screening, data collection, and ordering of up to 9 patients/minute while decreasing curbside specimen collection from more than 39 to less than 17 minutes per patient. The approach supported texting consumers and standards-based reporting to public health agencies.

Rapid Implementation of a Complex, Multimodal Technology Response to COVID-19 at an Integrated Community-Based Health Care System.

BACKGROUND: The rapid spread of severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 necessitated a scaled treatment response to the novel coronavirus disease 2019 (COVID-19). OBJECTIVE: This study aimed to characterize the design and rapid implementation of a complex, multimodal, technology response to COVID-19 led by the Intermountain Healthcare's (Intermountain's) Care Transformation Information Systems (CTIS) organization to build pandemic surge capacity. METHODS: Intermountain has active community-spread cases of COVID-19 that are increasing. We used the Centers for Disease Control and Prevention Pandemic Intervals Framework (the Framework) to characterize CTIS leadership's multimodal technology response to COVID-19 at Intermountain. We provide results on implementation feasibility and sustainability of health information technology (HIT) interventions as of June 30, 2020, characterize lessons learned and identify persistent barriers to sustained deployment. RESULTS: We characterize the CTIS organization's multimodal technology response to COVID-19 in five relevant areas of the Framework enabling (1) incident management, (2) surveillance, (3) laboratory testing, (4) community mitigation, and (5) medical care and countermeasures. We are seeing increased use of traditionally slow-to-adopt technologies that create additional surge capacity while sustaining patient safety and care quality. CTIS leadership recognized early that a multimodal technology intervention could enable additional surge capacity for health care delivery systems with a broad geographic and service scope. A statewide central tracking system to coordinate capacity planning and management response is needed. Order interoperability between health care systems remains a barrier to an integrated response. CONCLUSION: The rate of future pandemics is estimated to increase. The pandemic response of health care systems, like Intermountain, offers a blueprint for the leadership role that HIT organizations can play in mainstream care delivery, enabling a nimbler, virtual health care delivery system that is more responsive to current and future needs.

Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD.

BACKGROUND AND OBJECTIVES: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare pediatric disease of unknown cause. Here, in response to a recent case report describing a ROHHAD patient who suffered from secondary narcolepsy confirmed by an absence of hypocretin-1 in the cerebrospinal fluid, we consider whether the ROHHAD phenotype is owing to one or more mutations in genes specific to hypocretin protein signalling. METHODS: DNA samples from 16 ROHHAD patients were analyzed using a combination of next-generation and Sanger sequencing to identify exonic sequence variations in three genes: HCRT, HCRTR1, and HCRTR2. RESULTS: No rare or novel mutations were identified in the exons of HCRT, HCRTR1, or HCRTR2 genes in a set of 16 ROHHAD patients. CONCLUSIONS: ROHHAD is highly unlikely to be caused by mutations in the exons of the genes for hypocretin and its two receptors.

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.

BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation.

Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes.

CONTEXT: The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune ß-cell damage driven by excess weight. OBJECTIVE: The objective of the study was to address the question of whether the degree of ß-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. DESIGN: This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. SETTING: The study was conducted at a regional academic pediatric diabetes center. PATIENTS: Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. MAIN OUTCOME MEASURES: Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. RESULTS: There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P < .05). CONCLUSIONS: No evidence was found to support the concept that obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.

Monozygotic twins discordant for ROHHAD phenotype.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) falls within a group of pediatric disorders with both respiratory control and autonomic nervous system dysregulation. Children with ROHHAD typically present after 1.5 years of age with rapid weight gain as the initial sign. Subsequently, they develop alveolar hypoventilation, autonomic nervous system dysregulation, and, if untreated, cardiorespiratory arrest. To our knowledge, this is the first report of discordant presentation of ROHHAD in monozygotic twins. Twin girls, born at term, had concordant growth and development until 8 years of age. From 8 to 12 years of age, the affected twin developed features characteristic of ROHHAD including obesity, alveolar hypoventilation, scoliosis, hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, premature pubarche, and growth hormone deficiency), right paraspinal/thoracic ganglioneuroblastoma, seizures, and autonomic dysregulation including altered pain perception, large and sluggishly reactive pupils, hypothermia, and profound bradycardia that required a cardiac pacemaker. Results of genetic testing for PHOX2B (congenital central hypoventilation syndrome disease-defining gene) mutations were negative. With early recognition and conservative management, the affected twin had excellent neurocognitive outcome that matched that of the unaffected twin. The unaffected twin demonstrated rapid weight gain later in age but not development of signs/symptoms consistent with ROHHAD. This discordant twin pair demonstrates key features of ROHHAD including the importance of early recognition (especially hypoventilation), complexity of signs/symptoms and clinical course, and importance of initiating comprehensive, multispecialty care. These cases confound the hypothesis of a monogenic etiology for ROHHAD and indicate alternative etiologies including autoimmune or epigenetic phenomenon or a combination of genetic predisposition and acquired precipitant.

Progressive erosion of ß-cell function precedes the onset of hyperglycemia in the NOD mouse model of type 1 diabetes.

OBJECTIVE: A progressive decline in insulin responses to glucose was noted in individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred in prediabetic NOD mice-the prototypic model for human type 1 diabetes. RESEARCH DESIGN AND METHODS: Morning blood glucose was measured every other day in a cohort of NOD females. Glucose tolerance and insulin secretion were measured longitudinally by intraperitoneal glucose tolerance tests in NOD/ShiLtJ and BALB/cJ mice 6 to 14 weeks of age. Arginine-stimulated insulin secretion and insulin sensitivity were assessed during intraperitoneal arginine or intraperitoneal insulin tolerance tests. RESULTS: During prediabetes, NOD females displayed a progressive increase in glucose levels followed by an acute onset of hyperglycemia. First-phase insulin responses (FPIRs) during the intraperitoneal glucose tolerance test (IPGTT) declined before loss of glucose tolerance in NOD. The failure of FPIR could be detected, with a decline in peak insulin secretion during IPGTT. Arginine-stimulated insulin secretion remained unchanged during the study period. The decline in insulin secretion in NOD mice could not be explained by changes in insulin sensitivity. CONCLUSIONS: There was an impressive decline in FPIR before changes in glucose tolerance, suggesting that impairment of FPIR is an early in vivo marker of progressive ß-cell failure in NOD mice and human type 1 diabetes. We portend that these phenotypes in NOD mice follow a similar pattern to those seen in humans with type 1 diabetes and validate, in a novel way, the importance of this animal model for studies of this disease.

Evaluating protocols for embryonic stem cell differentiation into insulin-secreting beta-cells using insulin II-GFP as a specific and noninvasive reporter.

Stable and full differentiation of pluripotent stem cells into functional beta-cells offers the potential to treat type I diabetes with a theoretically inexhaustible source of replacement cells. In addition to the difficulties in directed differentiation, progress toward an optimized and reliable protocol has been hampered by the complication that cultured cells will concentrate insulin from the media, thus making it difficult to tell which, if any, cells are producing insulin. To address this, we utilized a novel murine embryonic stem cell (mESC) research model, in which the green fluorescent protein (GFP) has been inserted within the C-peptide of the mouse insulinII gene (InsulinII-GFP). Using this method, cells producing insulin are easily identified. We then compared four published protocols for differentiating mESCs into beta-cells to evaluate their relative efficiency by assaying intrinsic insulin production. Cells differentiated using each protocol were easily distinguished based on culture conditions and morphology. This comparison is strengthened because all testing is performed within the same laboratory by the same researchers, thereby removing interlaboratory variability in culture, cells, or analysis. Differentiated cells were analyzed and sorted based on GFP fluorescence as compared to wild type cells. Each differentiation protocol increased GFP fluorescence but only modestly. None of these protocols yielded more than 3% of cells capable of insulin biosynthesis indicating the relative inefficiency of all analyzed protocols. Therefore, improved beta-cells differentiation protocols are needed, and these insulin II GFP cells may prove to be an important tool to accelerate this process.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood.

OBJECTIVE: The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with hypothalamic dysfunction. METHODS: Individuals with late-onset central hypoventilation with hypothalamic dysfunction who were referred to Rush University Medical Center for clinical or genetic assessment in the past 3 years were identified, and medical charts were reviewed to determine shared characteristics of the affected subjects. Blood was collected for genetic testing of candidate genes (PHOX2B, TRKB, and BDNF) and for high-resolution conventional G-banding, subtelomeric fluorescent in situ hybridization, and comparative genomic hybridization analysis. A subset of these children were studied in the Pediatric Respiratory Physiology Laboratory at Rush University Medical Center. RESULTS: Twenty-three children with what we are now naming rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation were identified. Comprehensive medical charts and blood for genetic testing were available for 15 children; respiratory physiology studies were performed at Rush University Medical Center on 9 children. The most characteristic manifestations were the presentation of rapid-onset obesity in the first 10 years of life (median age at onset: 3 years), followed by hypothalamic dysfunction and then onset of symptoms of autonomic dysregulation (median age at onset: 3.6 years) with later onset of alveolar hypoventilation (median age at onset: 6.2 years). Testing of candidate genes (PHOX2B, TRKB, and BDNF) revealed no mutations or rare variants. High-resolution chromosome analysis, comparative genomic hybridization, and subtelomeric fluorescent in situ hybridization results were negative for the 2 patients selected for those analyses. CONCLUSIONS: We provide a comprehensive description of the clinical spectrum of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in terms of timing and scope of symptoms, study of candidate genes, and screening for chromosomal deletions and duplications. Negative PHOX2B sequencing results demonstrate that this entity is distinct from congenital central hypoventilation syndrome.

The classification of diabetes mellitus: a conceptual framework.

Diabetes is the extreme manifestation of a spectrum conditions in which the balance of insulin secretion and insulin action (or insulin resistance) has been altered. Loss of euglycemia is caused by relative insulin deficiency in the presence of insulin resistance, or by absolute insulin deficiency. There are related conditions in which an alteration of insulin resistance or beta-cell dysfunction exists, but because of compensation glucose homeostasis has not been lost. The elucidation of the causes of insulin resistance and -cell failure and the attention to the different degrees of insulin deficiency and insulin resistance allow for better diagnosis, treatment, and prevention of diabetes and its related conditions.

Neurotoxicities in infants seen with the consumption of star anise tea.

Chinese star anise (Illicium verum Hook f.) is a well-known spice used in many cultures. Many populations use it as a treatment for infant colic. Japanese star anise (Illicium anisatum L), however, has been documented to have both neurologic and gastrointestinal toxicities. Recently, concern has been raised regarding the adulteration of Chinese star anise with Japanese star anise. We report 7 cases of adverse neurologic reactions in infants seen with the home administration of star anise tea. In addition, we have found evidence that Chinese star anise has been contaminated with Japanese star anise. More strict federal regulation of the import of star anise into the United States is warranted. Star anise tea should no longer be administered to infants because of its potential danger in this population.