Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH.

BACKGROUND & AIMS: Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis. METHODS: Study 747-117 randomized 51 subjects with NASH (fibrosis stages F1-F4) to daily placebo, OCA 10 or OCA 25 mg (1:2:2) for 85 days. Study 747-118 randomized 24 subjects with NASH cirrhosis (F4; Child-Pugh [CP]-A) and normal liver control subjects matched for similar body weight to daily OCA 10 or OCA 25 mg (1:1) for 28 days. Individual and combined study data were analysed. RESULTS: No severe or serious adverse events (AEs) or AEs leading to discontinuation or death occurred. Pruritus was the most frequent AE. Plasma OCA exposure (dose-normalized area under the curve) increased with fibrosis stage but was a relatively poor predictor of hepatic OCA exposure (primary site of action), which remained constant across fibrosis stages F1-F3 and increased 1.8-fold compared with F1 in subjects with cirrhosis due to NASH. Both cohorts showed robust changes in farnesoid X receptor activation markers with OCA treatment and marked decreases in alanine transaminase, aspartate transaminase and gamma-glutamyltransferase. CONCLUSIONS: Despite higher drug exposures in subjects with NASH cirrhosis, short-term daily treatment with OCA 10 or 25 mg was generally safe and well tolerated in subjects with NASH fibrosis or NASH CP-A cirrhosis. Both cohorts experienced improvements in nonhistologic pharmacodynamic markers consistent with previously conducted OCA phase 2 and phase 3 studies in NASH fibrosis.

Objective Response of Saliva Biomarkers After High-Stress and Mass Casualty Scenarios: A Pilot Study.

INTRODUCTION: Surgeons and military personnel are subjected to high-stress scenarios, which leads to greater rates of burnout. There is room to optimize performance and longevity in these careers by better understanding the body's stress response and applying it to stress management training. This study aims to understand the physiological response in those engaged in trauma scenarios by examining 6 hormones and 42 cytokines during the Intensive Surgical and Trauma Skills Course held at Strategic Operations Inc in San Diego, CA. METHODS: Thirty-seven military medical students participated in full immersion, hyper-realistic, and experiential mass casualty high-stress scenarios. Participants were exposed to both operating and emergency room scenarios. Saliva samples were taken after stress inoculation (postinoculation) and again 1 hr after each scenario (recovery). Saliva samples were analyzed using plex assays from Eve Technologies. Data were grouped and analyzed by location and timing using mixed effect nonlinear models. Distributions were compared by location and were analyzed with respect to biomarker levels over the 4-day training period. RESULTS: For emergency room scenarios, there was a decrease in the following cytokines from postinoculation to recovery: epidermal growth factor (EGF), granulocyte colony stimulating factor (G-CSF), epidermal growth factor, granulocyte colony stimulating factor, interleukin 1alpha (IL-1α), interleukin 1beta (IL-1 ß), IL-1RA, IL-4, IL-8, IL-10, IL-18, monocyte chemotactic protein (MCP) 1, macrophage colony stimulating factor (M-CSF), macrophage derived chemokine (MDC), CXC motif ligand 9 (MIG/CXCL9), regulated upon activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (P < 0.05, t > 3.0). For operating room scenarios, there was a decrease in the following cytokines: EGF, G-CSF, IL-1α, IL-1 ß, IL-1RA, IL-6, IL-8, IL-10, IL-18, M-CSF, MDC, MIG/CXCL9, RANTES, and tumor necrosis factor alpha. In operating room scenarios, an increase in the hormone levels of progesterone and triodothyronine were observed. The cytokines observed in both groups included EGF, IL-1α, RANTES, MDC, EGF, G-CSF, IL-1RA, IL-18, MIG/CXCL9, IL-8, IL-1ß, M-CSF, and IL-10. These significant biomarkers were also graphed and visualized as variable throughout the week. CONCLUSIONS: These preliminary data narrow a wide array of stress biomarkers to a smaller, significant group. Surgeons and military personnel are subjected to extraordinary levels of stress with narrow margins for error. To optimize performance and outcomes, it is pertinent to understand the physiological stress response. Future investigation and pairing of cytokine measurements with neuropsychological and performance-based testing will target opportunities to direct training and identify profiles of individuals well suited for stressful environments.

Sustained increase in annual transcranial Doppler screening rates in children with sickle cell disease: A quality improvement project.

INTRODUCTION: Individuals with sickle cell disease (SCD) at increased risk for stroke should undergo annual stroke risk assessment using transcranial Doppler (TCD) screening between the ages of 2 and 16. Though this screening can significantly reduce morbidity associated with SCD, screening rates at Boston Children's Hospital (and nationwide) remain below the recommended 100% screening adherence rates. METHODS: Three plan-do-study-act (PDSA) cycles were designed and implemented. The Specific, Measurable, Achievable, Relevant, and Time-Bound (SMART) aim of our quality improvement (QI) initiative was to sustainably increase the proportion of eligible patients receiving a TCD within 15 months of their last TCD to greater than 95%. An interrupted time series (ITS) analysis was performed, comparing TCD adherence rates from PDSA Cycle 1 to those from PDSA Cycles 2 and 3. RESULTS: Mean TCD adherence increased across all three PDSA cycles, from a baseline of 67% in the first cycle (January 2015 to September 2020) to 92% in the third cycle (May 2021 to March 2023). In the ITS analysis of TCD adherence rates, there was a significant difference in the final TCD adherence rate achieved compared to the rate predicted, with a total estimated increase in adherence of 17.9% being attributable to the interventions from PDSA Cycles 2 and 3. DISCUSSION: Although other QI initiatives had demonstrated ability to increase adherence to TCD screening for patients with SCD, this is the first QI project to collect data over such a prolonged period of time to demonstrate a sustained increase in screening rates throughout the intervention (an 8-year period).

Taste-masked formulation of sodium phenylbutyrate (ACER-001) for the treatment of urea cycle disorders.

Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. Defects in these enzymes lead to acute accumulation (hyperammonemic crises, HAC) or chronically elevated levels (hyperammonemia) of ammonia in the blood and/or various tissues including the brain, which can cause persistent neurological deficits, irreversible brain damage, coma, and death. Ongoing treatment of UCDs include the use of nitrogen-scavenging agents, such as sodium phenylbutyrate (salt of 4-phenylbutyric acid; NaPBA) or glycerol phenylbutyrate (GPB). These treatments provide an alternative pathway for nitrogen disposal through the urinary excretion of phenylacetylglutamine. ACER-001 is a novel formulation of NaPBA with polymer coated pellets in suspension, which is designed to briefly mask the unpleasant bitter taste of NaPBA and is being developed as a treatment option for patients with UCDs. Four Phase 1 studies were conducted to characterize the bioavailability (BA) and/or bioequivalence (BE) of ACER-001 (in healthy volunteers) and taste assessment relative to NaPBA powder (in taste panelists). ACER-001 was shown to be bioequivalent to NaPBA powder under both fed and fasting conditions. Lower systemic exposure of phenylacetate (PAA) and phenylbutyrate (PBA) was observed when ACER-001 was administered with a high-fat meal relative to a fasting state suggesting that the lower doses of PBA administered under fasting conditions may yield similar efficacy with potentially fewer dose dependent adverse effects relative to higher doses with a meal. ACER-001 appeared to be adequately taste-masked, staying below the aversive taste threshold for the first 3 min after the formulation was prepared and remaining palatable when taken within 5 min.

Group Concept Mapping Conceptualizes High-Quality Care for Long-Stay Pediatric Intensive Care Unit Patients and Families.

OBJECTIVE: To describe and conceptualize high-quality care for long-stay pediatric intensive care unit (PICU) patients using group concept mapping (GCM). STUDY DESIGN: We convened an expert panel to elucidate domains of high-quality care for this growing patient population for which transitory care models fail to meet their needs. Thirty-one healthcare professionals and 7 parents of patients with previous prolonged PICU hospitalizations comprised a diverse, interprofessional multidisciplinary panel. Participants completed the prompt "For PICU patients and families experiencing prolonged lengths of stay, high quality care from the medical team includes ______", with unlimited free text responses. Responses were synthesized into individual statements, then panelists sorted them by idea similarity and rated them by perceived importance. Statement analysis using GCM software through GroupWisdom generated nonoverlapping clusters representing domains of high-quality care. RESULTS: Participants submitted 265 prompt responses representing 313 unique ideas, resulting in 78 final statements for sorting and rating. The resultant cluster map best representing the data contained 8 domains: (1) Family-Centered Care and Shared Decision Making, (2) Humanizing the Patient, (3) Clinician Supports and Resources, (4) Multidisciplinary Coordination of Care, (5) Family Well-Being, (6) Anticipatory Guidance and Care Planning, (7) Communication, and (8) Continuity of Care. CONCLUSIONS: GCM empowered a panel of healthcare professionals and parents to explicitly describe and conceptualize high-quality care for patients and families experiencing prolonged PICU stays. This information will aid the effort to address shortcomings of transitory PICU care models.

Cloud-based fusion imaging improves operative metrics during fenestrated endovascular aneurysm repair.

OBJECTIVE: Endovascular treatment of complex aortic pathology has been associated with increases in procedural-related metrics, including the operative time and radiation exposure. Three-dimensional fusion imaging technology has decreased the radiation dose and iodinated contrast use during endovascular aneurysm repair. The aim of the present study was to report our institutional experience with the use of a cloud-based fusion imaging platform during fenestrated endovascular aneurysm repair (FEVAR). METHODS: A retrospective review of a prospectively maintained aortic database was performed to identify all patients who had undergone FEVAR with commercially available devices (Zenith Fenestrated; Cook Medical Inc, Bloomington, IN) between 2013 and 2020 and all endovascular aneurysm repairs performed using Cydar EV Intelligent Maps (Cydar Medical, Cambridge, UK). The Cydar EV cohort was reviewed further to select all FEVARs performed with overlay map guidance. The patient demographic, clinical, and procedure metrics were analyzed, with a comparative analysis of FEVAR performed without and with the Cydar EV imaging platform. Patients were excluded from comparative analysis if the data were incomplete in the dataset or they had a documented history of prior open or endovascular abdominal aortic aneurysm repair. RESULTS: During the 7-year study period, 191 FEVARs had been performed. The Cydar EV imaging platform was implemented in 2018 and used in 124 complex endovascular aneurysm repairs, including 69 consecutive FEVARs. A complete dataset was available for 137 FEVARs. With exclusion to select for de novo FEVAR, a comparative analysis was performed of 53 FEVAR without and 63 with Cydar EV imaging guidance. The cohorts were similar in patient demographics, medical comorbidities, and aortic aneurysm characteristics. No significant difference was noted between the two groups for major adverse postoperative events, length of stay, or length of intensive care unit stay. The use of Cydar EV resulted in nonsignificant decreases in the mean fluoroscopy time (69.3 ± 28 minutes vs 66.2 ± 33 minutes; P = .598) and operative time (204.4 ± 64 minutes vs 186 ± 105 minutes; P = .278). A statistically significant decrease was found in the iodinated contrast volume (105 ± 44 mL vs 83 ± 32 mL; P = .005), patient radiation exposure using the dose area product (1,049,841 mGy/cm2 vs 630,990 mGy/cm2; P < .001) and cumulative air kerma levels (4518 mGy vs 3084 mGy; P = .02) for patients undergoing FEVAR with Cydar EV guidance. CONCLUSIONS: At our aortic center, we have observed a trend toward shorter operative times and significant reductions in both iodinated contrast use and radiation exposure during FEVAR using the Cydar EV intelligent maps. Intelligent map guidance improved the efficiency of complex endovascular aneurysm repair, providing a safer intervention for both patient and practitioner.

Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity.

Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.

Parental Adverse Childhood Experiences and Post-PICU Stress in Children and Parents.

OBJECTIVES: Hospitalization in a PICU is a stressful experience for children and their parents, with many experiencing posttraumatic stress disorder (PTSD) after discharge. Risk factors may include preillness traumatic events, such as adverse childhood experiences (ACEs). We sought to assess the feasibility of screening ACEs in parents of children admitted to a PICU, their prevalence, and their association with post-PICU PTSD symptoms in them and their children. DESIGN: Single-center prospective observational study. SETTING: Urban academic children's hospital from January to December 2021. PATIENTS: One hundred forty-five children (2-18 yr old, admitted ≥ 2 d) and their parents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on parental demographics, ACEs, coping skills, and PICU environmental stressors, as well as patient clinical data, were collected. One month after PICU discharge, parents completed inventories assessing PTSD symptoms in them and their children. Bivariate and logistic regression analyses were used to explore associations of ACEs with post-PICU PTSD. Of 145 enrolled parents, 95% completed the ACE questionnaire, 58% of whom reported greater than or equal to 1 ACE, and 14% had substantial (≥ 4) ACEs. Parent and patient follow-up was 79% and 70%, respectively. Sixteen percent of parents had provisional PTSD. Regression analysis showed parents with greater than or equal to 4 ACEs had 10 times greater odds of parental PTSD, compared to parents with less than 4 ACEs, (adjusted odds ratio [aOR] = 10.2; 95% CI, 1.03-100.9; p = 0.047). Fifty-six percent of patients screened at risk for PTSD. There was no association between substantial parental ACEs and patients' risk for PTSD (aOR = 3.5 [95% CI, 0.56-21.31]; p = 0.18). CONCLUSIONS: ACEs were common among parents of critically ill children. Having substantial parental ACEs was associated with provisional parental PTSD after their child's PICU admission, but not with PTSD in the children. Family-centered care that seeks to mitigate post-PICU stress should be mindful of the potential relevance of parental ACEs.

Primary Intensivists and Nurses for Long-Stay Patients: A Survey of Practices and Perceptions at Academic PICUs.

OBJECTIVES: To determine the prevalence of the utilization of primary intensivists and primary nurses for long-stay patients in large, academic PICU and ascertain how these practices are operationalized and perceived. DESIGN: A cross-sectional survey. SETTING: U.S. PICUs with accredited Pediatric Critical Care Medicine fellowships. SUBJECTS: One senior physician and one senior nurse at each institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Separate but largely analogous questionnaires for intensivists and nurses were created using an iterative process to enhance content/face validity and readability. Sixty-seven intensivists (representing 93% of the 72 institutions with fellowship programs and their PICUs) and 59 nurses (representing 82%) responded. Twenty-four institutions utilize primary intensivists; 30 utilize primary nurses; and 13 utilize both. Most institutions use length of stay and/or other criteria (e.g., medical complexity) for eligibility. Commonly, not all patients that meet eligibility criteria receive primaries. Primary providers are overwhelmingly volunteers, and often only a fraction of providers participate. Primary intensivists at a large majority (>75%) of institutions facilitate information sharing and decision-making, attend family/team meetings, visit patients/families regularly, and are otherwise available upon request. Primary nurses at a similar majority of institutions provide consistent bedside care, facilitate information sharing, and attend family/team meetings. A large majority of respondents thought that primary intensivists increase patient/family satisfaction, reduce their stress, improve provider communication, and reduce conflict, whereas primary nurses similarly increase patient/family satisfaction. More than half of respondents shared that these practices can sometimes require effort (e.g., time and emotion), complicate decision-making, and/or reduce staffing flexibility. CONCLUSIONS: Primary practices are potential strategies to augment rotating PICU care models and better serve the needs of long-stay and other patients. These practices are being utilized to varying extents and with some operationalization uniformity at large, academic PICUs.

Continuity Strategies for Long-Stay PICU Patients: Consensus Statements From the Lucile Packard Foundation PICU Continuity Panel.

OBJECTIVES: To develop consensus statements on continuity strategies using primary intensivists, primary nurses, and recurring multidisciplinary team meetings for long-stay patients (LSPs) in PICUs. PARTICIPANTS: The multidisciplinary Lucile Packard Foundation PICU Continuity Panel comprising parents of children who had prolonged PICU stays and experts in several specialties/professions that care for children with medical complexity in and out of PICUs. DESIGN/METHODS: We used modified RAND Delphi methodology, with a comprehensive literature review, Delphi surveys, and a conference, to reach consensus. The literature review resulted in a synthesized bibliography, which was provided to panelists. We used an iterative process to generate draft statements following panelists' completion of four online surveys with open-ended questions on implementing and sustaining continuity strategies. Panelists were anonymous when they voted on revised draft statements. Agreement of 80% constituted consensus. At a 3-day virtual conference, we discussed, revised, and re-voted on statements not reaching or barely reaching consensus. We used Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of the evidence and rate the statements' strength. The Panel also generated outcome, process, and balancing metrics to evaluate continuity strategies. RESULTS: The Panel endorsed 17 consensus statements in five focus areas of continuity strategies (Eligibility Criteria, Initiation, Standard Responsibilities, Resources Needed to Implement, Resources Needed to Sustain). The quality of evidence of the statements was low to very low, highlighting the limited evidence and the importance of panelists' experiences/expertise. The strength of the statements was conditional. An extensive list of potential evaluation metrics was generated. CONCLUSIONS: These expert/parent-developed consensus statements provide PICUs with novel summaries on how to operationalize, implement, and sustain continuity strategies for LSP, a rapidly growing, vulnerable, resource-intensive population in PICUs.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017-2019.

Objectives: To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence. Methods: This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results: Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion: In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia.

Objective: To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods: This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results: There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions: While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory-e.g., the amygdala and hippocampus-are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing ß-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.

The Child With Severe Chronic Illness in the ICU: A Concise Review.

OBJECTIVES: Children with severe chronic illness are a prevalent, impactful, vulnerable group in PICUs, whose needs are insufficiently met by transitory care models and a narrow focus on acute care needs. Thus, we sought to provide a concise synthetic review of published literature relevant to them and a compilation of strategies to address their distinctive needs. DATA SOURCES: English language articles were identified in MEDLINE using a variety of phrases related to children with chronic conditions, prolonged admissions, resource utilization, mortality, morbidity, continuity of care, palliative care, and other critical care topics. Bibliographies were also reviewed. STUDY SELECTION: Original articles, review articles, and commentaries were considered. DATA EXTRACTION: Data from relevant articles were reviewed, summarized, and integrated into a narrative synthetic review. DATA SYNTHESIS: Children with serious chronic conditions are a heterogeneous group who are growing in numbers and complexity, partly due to successes of critical care. Because of their prevalence, prolonged stays, readmissions, and other resource use, they disproportionately impact PICUs. Often more than other patients, critical illness can substantially negatively affect these children and their families, physically and psychosocially. Critical care approaches narrowly focused on acute care and transitory/rotating care models exacerbate these problems and contribute to ineffective communication and information sharing, impaired relationships, subpar and untimely decision-making, patient/family dissatisfaction, and moral distress in providers. Strategies to mitigate these effects and address these patients' distinctive needs include improving continuity and communication, primary and secondary palliative care, and involvement of families. However, there are limited outcome data for most of these strategies and little consensus on which outcomes should be measured. CONCLUSIONS: The future of pediatric critical care medicine is intertwined with that of children with serious chronic illness. More concerted efforts are needed to address their distinctive needs and study the effectiveness of strategies to do so.

Food Insecurity and Delayed or Forgone Medical Care During the COVID-19 Pandemic.

Objectives. To describe food insecurity in the United States in December 2020 and examine associations with underuse of medical care during the COVID-19 pandemic. Methods. We fielded a nationally representative Web-based survey in December 2020 (n = 8318). Multivariable logistic regression models and predicted probabilities were used to evaluate factors associated with food insecurity and compare the likelihood of delaying or forgoing medical care because of cost concerns by food security status. Results. In December 2020, 18.8% of US adults surveyed reported experiencing food insecurity. Elevated odds of food insecurity were observed among non-Hispanic Black, Hispanic, and low-income respondents. Experiencing food insecurity was significantly associated with a greater likelihood of forgoing any type of medical care as a result of cost concerns. Conclusions. Food insecurity during the COVID-19 pandemic disproportionately affected non-White and low-income individuals. Experiencing food insecurity was a significant risk factor for delaying or forgoing medical care, an association that could have cumulative short- and long-term health effects. Public Health Implications. Comprehensive policies that target the most at-risk groups are needed to address the high rates of food insecurity in the United States and mitigate its adverse health effects. (Am J Public Health. 2022;112(5):776-785. https://doi.org/10.2105/AJPH.2022.306724).

A Single-Centered Randomized Controlled Trial of Primary Pediatric Intensivists and Nurses.

Background: For long-stay patients (LSP) in pediatric intensive care units (PICU), frequently rotating providers can lead to ineffective information sharing and retention, varying goals and timelines, and delayed decisions, likely contributing to prolonged admissions. Primary intensivists (one physician serves as a consistent resource for the patient/family and PICU providers) and primary nurses (a small team of PICU nurses provide consistent bedside care) seek to augment usual transitory PICU care, by enhancing continuity and, potentially, decreasing length of stay (LOS). Methods: A single-centered, partially blinded randomized controlled trial of primary intensivists and nurses versus usual care. PICU patients admitted for or expected to be admitted for >10 days and who had ≥1 complex chronic condition were eligible. A block randomization with 1:1 allocation was used. The primary outcome was PICU LOS. Multiple secondary outcomes were explored. Results: Two hundred LSPs were randomized-half to receive primaries and half to usual care. The two groups were not significantly different in their baseline and admission characteristics. LSPs randomized to receive primaries had a shorter, but non-significant, mean LOS than those randomized to usual care (32.5 vs. 37.1 days, respectively, p = .19). Compared to LSPs in the usual care group, LSPs in the primary group had fewer unplanned intubations. Among LSPs that died, DNR orders were more prevalent in the primary group. Other secondary outcome and balance metrics were not significantly different between the two groups. Conclusion: Primary intensivists and nurses may be an effective strategy to counteract transitory PICU care and serve the distinctive needs of LSPs. However, additional studies are needed to determine the ways and to what extent they may accomplish this.

Delayed care in myocardial infarction and ischemic stroke patients during the COVID-19 pandemic.

COVID-19 has profound direct health consequences, however secondary effects were much broader as rates of hospital visits steeply declined for non-COVID-19 concerns, including myocardial infarction (MI) and stroke, with patients choosing to wait longer before symptoms convince them to seek medical attention. Thus, patients where ischemia leads to tissue loss should be a major concern. METHODS: The months of March to June 2019 and 2020 were compared to each other at 4 Denver area hospitals. Reduction in overall ED visits and an increase in patient refusal for emergency transport were clear in the data collected. During this period in 2019, 49 MI and 90 stroke patients were admitted. In 2020 this was 40 and 90 respectively. All were matched for age and gender. For MI patients ejection fraction and door to EKG and intervention times were measured. For stroke patients last known well time, time to evaluation, and modified Rankin scores were measured. RESULTS: 254 (8.12%) patients refused emergency services transportation before the pandemic compared to 479 (18.35%) during the pandemic (p-value <0.001, chi square test). In the MI cohort, no significant difference was detected in measured ejection fraction (48% vs 49% p-value = 0.682). Additionally, no significant difference was detected between door to EKG time or door to MI intervention time. During the pandemic 8 (22%) expired with an MI prior to discharge, compared to 2 (4%) before the pandemic. The stroke cohort Door to Evaluation Time, Time since last well known, and modified Rankin scores were all found to have insignificant differences. DISCUSSION: ED volume was significantly lower during the early stages of the pandemic. During this time however only death from cardiac events increased, in spite of similar ejection fractions at discharge. The cause of this remains unclear as ejection fraction similarities make it less attributable to loss of tissue than to other factors. Patient behavior significantly changed during the pandemic, making this a likely source of the increase in mortality seen.

Long-Term Increases in Mental Disorder Diagnoses After Invasive Mechanical Ventilation for Severe Childhood Respiratory Disease: A Propensity Matched Observational Cohort Study.

OBJECTIVES: To evaluate neurodevelopmental and mental disorders after PICU hospitalization in children requiring invasive mechanical ventilation for severe respiratory illness. DESIGN: Retrospective longitudinal observational cohort. SETTING: Texas Medicaid Analytic eXtract data from 1999 to 2012. PATIENTS: Texas Medicaid-enrolled children greater than or equal to 28 days old to less than 18 years old hospitalized for a primary respiratory illness, without major chronic conditions predictive of abnormal neurodevelopment. INTERVENTIONS: We examined rates of International Classification of Diseases, 9th revision-coded mental disorder diagnoses and psychotropic medication use following discharge among children requiring invasive mechanical ventilation for severe respiratory illness, compared with general hospital patients propensity score matched on sociodemographic and clinical characteristics prior to admission. Children admitted to the PICU for respiratory illness not necessitating invasive mechanical ventilation were also compared with matched general hospital patients as a negative control exposure. MEASUREMENTS AND MAIN RESULTS: Of 115,335 eligible children, 1,351 required invasive mechanical ventilation and were matched to 6,755 general hospital patients. Compared with general hospital patients, children requiring invasive mechanical ventilation had increased mental disorder diagnoses (hazard ratio, 1.43 [95% CI, 1.26-1.64]; p < 0.0001) and psychotropic medication use (hazard ratio, 1.67 [1.34-2.08]; p < 0.0001) following discharge. Seven-thousand seven-hundred eighty children admitted to the PICU without invasive mechanical ventilation were matched to 38,900 general hospital patients and had increased mental disorder diagnoses (hazard ratio, 1.08 [1.02-1.15]; p = 0.01) and psychotropic medication use (hazard ratio, 1.11 [1.00-1.22]; p = 0.049). CONCLUSIONS: Children without major comorbidity requiring invasive mechanical ventilation for severe respiratory illness had a 43% higher incidence of subsequent mental disorder diagnoses and a 67% higher incidence of psychotropic medication use. Both increases were substantially higher than in PICU patients with respiratory illness not necessitating invasive mechanical ventilation. Invasive mechanical ventilation is a life-saving therapy, and its application is interwoven with underlying health, illness severity, and PICU management decisions. Further research is required to determine which factors related to invasive mechanical ventilation and severe respiratory illness are associated with abnormal neurodevelopment. Given the increased risk in these children, identification of strategies for prevention, neurodevelopmental surveillance, and intervention after discharge may be warranted.

Early retention among pregnant women on 'Option B + ' in urban and rural Zimbabwe.

BACKGROUND: In 2013, the World Health Organisation (WHO) recommended Option B+ as a strategy to prevent mother-to-child transmission (PMTCT) of HIV. In option B+ , lifelong antiretroviral therapy (ART) is offered to all HIV positive pregnant and breastfeeding women to reduce MTCT rate to less than or equal to 5%. Its success depends on retaining women on ART during pregnancy, delivery and breast-feeding period. There is limited data on early retention on ART among pregnant women in Zimbabwe. We therefore assessed early retention among women on Option B + from antenatal care (ANC) until 6 months post ANC booking and at delivery in Bulawayo city and Mazowe rural district of Zimbabwe. METHODS: We collected data for pregnant women booking for ANC between January and March 2018, comparing early retention among ART naïve women and those already on ART. The two cohorts were followed up for 6 months post ANC booking, and this was done in two districts. Data were collected from routine tools used at facility level which include ANC, delivery and ART registers. The Kaplan-Meier survival analysis was used to estimate retention probabilities at 1, 3 and 6 months post-delivery and for retention at delivery proportions were used. Poisson regression was used to investigate factors associated with non-retention at 6 months post ANC booking. RESULTS: A total of 388 women were included in the study with median age of 29 years (IQR: 25-34). Two-thirds booked in their second trimester. Retention at 3 and 6 months post ANC booking was 84% (95% CI 80-88) and 73% (95% CI 69-78) respectively. At delivery 81% (95% CI 76-84) were retained in care, 18% lost-to-follow-up and 1% transferred out. In this study we did not find marital status, gestation age, facility location, ART status at ANC booking, to be associated with loss to follow-up. CONCLUSION: In this study, we found low retention at 3, 6 months and delivery, a threat to elimination of Mother-to-child Transmission of HIV in Zimbabwe. Our findings emphasize the need for enhanced interventions to improve early retention such as post-test counselling, patient tracing and visit reminders.

Perceived consequences of healthcare service decentralization on access, affordability and quality of care in Khartoum locality, Sudan.

BACKGROUND: Decentralization of healthcare services has been widely utilized, especially in developing countries, to improve the performance of healthcare systems by increasing the access and efficiency of service delivery. Experiences have been variable secondary to disparities in financial and human resources, system capacity and community engagement. Sudan is no exception and understanding the perceived effect of decentralization on access, affordability, and quality of care among stakeholders is crucial. METHODS: This was a mixed method, cross-sectional, explorative study that involved 418 household members among catchment areas and 40 healthcare providers of Ibrahim Malik Hospital (IBMH) and Khartoum Teaching Hospital (KTH). Data was collected through a structured survey and in-depth interviews from July-December 2015. RESULTS: Access, affordability and quality of healthcare services were all perceived as worse, compared to before decentralization was implemented. Reported affordability was found to be 53 and 55% before decentralization compared to 24 to 16% after decentralization, within KTH and IBMH catchment areas respectively, (p = 0.01). The quality of healthcare services was reported to have declined from 47 and 38% before decentralization to 38 and 28% after, in KTH and IBMH respectively (p = 0.02). Accessibility was found to be more limited, with services being accessible before decentralization approximately 59 and 52% of the time, compared to 41 and 30% after, in KTH and IBMH catchment areas respectively, (p = 0.01). Accessibility to healthcare was reported to have decreased secondary to facility closures, reverse transference of services, and low capacity of devolved facilities. Lastly, privatized services were reported as strengthened in response to this decentralization of healthcare. CONCLUSIONS: The deterioration of access, affordability and quality of health services was experienced as the predominant perception among stakeholders after decentralization implementation. Our study results suggest there is an urgent need for a review of the current healthcare policies, structure and management within Sudan in order to provide evidence and insights regarding the impact of decentralization.