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Objective: To estimate the prevalence of chronic conditions among children admitted to U.S. pediatric intensive care units and to assess whether patients with complex chronic conditions experience pediatric intensive care unit mortality and prolonged length of stay risk beyond that predicted by commonly used severity-of-illness risk-adjustment models.Design, Setting, and Patients: Retrospective cohort analysis of 52,791 pediatric admissions to 54 U.S. pediatric intensive care units that participated in the Virtual Pediatric Intensive Care Unit Systems database in 2008.Measurements: Hierarchical logistic regression models, clustered by pediatric intensive care unit site, for pediatric intensive care unit mortality and length of stay >15 days. Standardized mortality ratios adjusted for severity-of-illness score alone and with complex chronic conditions.Main Results: Fifty-three percent of pediatric intensive care unit admissions had complex chronic conditions, and 18.5% had noncomplex chronic conditions. The prevalence of these conditions and their organ system subcategories varied considerably across sites. The majority of complex chronic condition subcategories were associated with significantly greater odds of pediatric intensive care unit mortality (odds ratios 1.25-2.9, all p values < .02) compared to having a noncomplex chronic condition or no chronic condition, after controlling for age, gender, trauma, and severity-of-illness. Only respiratory, gastrointestinal, and rheumatologic/orthopedic/psychiatric complex chronic conditions were not associated with increased odds of pediatric intensive care unit mortality. All subcategories were significantly associated with prolonged length of stay. All noncomplex chronic condition subcategories were either not associated or were negatively associated with pediatric intensive care unit mortality, and most were not associated with prolonged length of stay, compared to having no chronic conditions. Among this group of pediatric intensive care units, adding complex chronic conditions to risk-adjustment models led to greater model accuracy but did not substantially change unit-level standardized mortality ratios.Conclusions: Children with complex chronic conditions were at greater risk for pediatric intensive care unit mortality and prolonged length of stay than those with no chronic conditions, but the magnitude of risk varied across subcategories. Inclusion of complex chronic conditions into models of pediatric intensive care unit mortality improved model accuracy but had little impact on standardized mortality ratios. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., Competing Interests: Drs. Edwards’, Wocial’s, and Leland’s institutions received funding from the Lucile Packard Foundation for Children’s Health, Palo Alto, CA (no. 2020-05922). Dr. Wocial received support for article research from the Lucile Packard Foundation for Children’s Health, Palo Alto, CA (no. 2020-05922). As a family panelist and per Lucile Packard Foundation policy for such participants, the Lucile Packard Foundation provided Dr. Moon with a stipend to compensate her for the time spent on the project. Dr. Walter’s institution received funding from the National Heart, Lung, and Blood Institute; she received support for article research from the National Institutes of Health. Dr. Baird’s institution received funding from the Agency for Healthcare Research and Quality and Health Resources and Services Administration; she received funding from the I-PASS Patient Safety Institute and Patient-Centered Outcomes Research Institute. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., Competing Interests: Dr. Aponte-Patel received funding from the Columbia University Department of Psychiatry and NYP Weill Cornell. Dr. Baird received funding from I-PASS Patient Safety Institute. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Pregnancy-associated stroke carries high short-term morbidity and mortality, but data on subsequent maternal outcomes are limited. We evaluated long-term maternal health outcomes after pregnancy-associated stroke., Methods: In this retrospective cohort study, we used administrative data to identify pregnant adults aged ≤49 years with stroke between 2002-2020 in Ontario, Canada and 2 comparison groups: (1) non-pregnant female patients with stroke and (2) pregnant patients without stroke. Patients who survived the index admission were followed until 2021. After propensity score matching, we used Cox regression with a robust variance estimator to compare pregnant patients with stroke and the 2 comparison groups for the composite outcome of death and all-cause non-pregnancy readmission. Where proportional hazard assumption was not met, we reported time-varying hazard ratios (HR) with 95% CIs by modeling the log-hazard ratio as a function of time using restricted cubic splines., Results: We identified 217 pregnant patients with stroke, 7604 non-pregnant patients with stroke, and 1 496 256 pregnant patients without stroke. Of the 202 pregnant patients with stroke who survived the index stroke admission, 41.6% (6.8 per 100 person-years) subsequently died or were readmitted during follow-up. Median follow-up times were 5 years (pregnancy-associated stroke), 3 years (non-pregnant stroke), and 8 years (pregnant without stroke). Pregnant patients with stroke had a lower hazard of death and all-cause readmission compared with non-pregnant patients with stroke at 1-year follow-up (HR, 0.64 [95% CI, 0.44-0.94]), but this association did not persist during longer-term follow-up. Conversely, pregnant patients with stroke had higher hazard of death and readmission compared with pregnant patients without stroke at 1-year follow-up (HR, 5.70 [95% CI, 3.04-10.66]), and this association persisted for a decade., Conclusions: Stroke during pregnancy is associated with long-term health consequences. It is essential to transition care postpartum to primary or specialty care to optimize vascular health.

Background and Objectives: Sex differences in stroke care and outcomes have been previously reported, but it is not known whether these associations vary across the age continuum. We evaluated whether the magnitude of female-male differences in care and outcomes varied with age., Methods: In a population-based cohort study, we identified patients hospitalized with ischemic stroke between 2012 and 2019 and followed through 2020 in Ontario, Canada, using administrative data. We evaluated sex differences in receiving intensive care unit services, mechanical ventilation, gastrostomy tube insertion, comprehensive stroke center care, stroke unit care, thrombolysis, and endovascular thrombectomy using logistic regression and reported odds ratios (ORs) and 95% CIs. We used Cox proportional hazard models and reported the hazard ratios (HRs) and 95% CI of death within 90 or 365 days. Models were adjusted for covariates and included an interaction between age and sex. We used restricted cubic splines to model the relationship between age and care and outcomes. Where the p -value for interaction was statistically significant ( p < 0.05), we reported age-specific OR or HR., Results: Among 67,442 patients with ischemic stroke, 45.9% were female and the median age was 74 years (64-83). Care was similar between both sexes, except female patients had higher odds of receiving endovascular thrombectomy (OR 1.35, 95% CI [1.19-1.54] comparing female with male), and these associations were not modified by age. There was no overall sex difference in hazard of death (HR 95% CI 0.99 [0.95-1.04] for death within 90 days; 0.99 [0.96-1.03] for death within 365 days), but these associations were modified by age with the hazard of death being higher in female than male patients between the ages of 50-70 years (most extreme difference around age 57, HR 95% CI 1.25 [1.10-1.40] at 90 days, p-interaction 0.002; 1.15 [1.10-1.20] at 365 days, p-interaction 0.002)., Discussion: The hazard of death after stroke was higher in female than male patients aged 50-70 years. Examining overall sex differences in outcomes without accounting for the effect modification by age may miss important findings in specific age groups., (© 2022 American Academy of Neurology.)

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., Competing Interests: Dr. Goodman received funding from Elsevier Publishing, McGraw-Hill, the American College of Physician Advisors, and the Society of Critical Care Medicine. Dr. Edwards has disclosed that he does not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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., Competing Interests: Dr. Geneslaw received funding from the Columbia University Department of Pediatrics Innovation Nucleation Fund. Dr. Hua’s institution received funding from the National Institute on Aging and the American Federation for Aging Research, and she received support for article research from the National Institutes of Health (NIH). Dr. Ing was supported by the Agency for Healthcare Research and Quality (AHRQ) under award number K08HS022941. Dr. Ing’s institution received funding from the AHRQ and the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression., Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003-2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke., Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24-1.98]) and incident dementia (aHR Depression =1.85 [1.40-2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12-1.29]; aHR Depression =1.19 [1.04-1.37]), incident dementia (aHR Diabetes =1.14 [1.06-1.23]; aHR Depression =1.27 [1.08-1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10-1.26]; aHR Depression =1.24 [1.07-1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23-1.36]; aHR Depression =1.16 [1.05-1.29])., Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

Objective: To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias., Methods: We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning., Results: In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [-0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific sign of AD., Conclusions: Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy., (© 2018 American Academy of Neurology.)

Objectives: To determine the occurrence rate of unplanned readmissions to PICUs within 1 year and examine risk factors associated with repeated readmission., Design: Retrospective cohort analysis., Setting: Seventy-six North American PICUs that participated in the Virtual Pediatric Systems, LLC (VPS, LLC, Los Angeles, CA)., Patients: Ninety-three thousand three hundred seventy-nine PICU patients discharged between 2009 and 2010., Interventions: None., Measurements and Main Results: Index admissions and unplanned readmissions were characterized and their outcomes compared. Time-to-event analyses were performed to examine factors associated with readmission within 1 year. Eleven percent (10,233) of patients had 15,625 unplanned readmissions within 1 year to the same PICU; 3.4% had two or more readmissions. Readmissions had significantly higher PICU mortality and longer PICU length of stay, compared with index admissions (4.0% vs 2.5% and 2.5 vs 1.6 d; all p < 0.001). Median time to readmission was 30 days for all readmissions, 3.5 days for readmissions during the same hospitalization, and 66 days for different hospitalizations. Having more complex chronic conditions was associated with earlier readmission (adjusted hazard ratio, 2.9 for one complex chronic condition; hazard ratio, 4.8 for two complex chronic conditions; hazard ratio, 9.6 for three or more complex chronic conditions; all p < 0.001 compared no complex chronic condition). Most specific complex chronic condition conferred a greater risk of readmission, and some had considerably higher risk than others., Conclusions: Unplanned readmissions occurred in a sizable minority of PICU patients. Patients with complex chronic conditions and particular conditions were at much higher risk for readmission.

Objectives: To characterize patients who received tracheostomies for airway compromise or were initiated on long-term ventilation for chronic respiratory failure in PICUs and to examine variation in the incidence of initiation, patient characteristics, and modalities across sites., Design: Retrospective cross-sectional analysis., Settings: Seventy-three North American PICUs that participated in the Virtual Pediatric Systems, LLC., Patients: PICU patients admitted between 2009 and 2011., Interventions: None., Measurements and Main Results: Among 115,437 PICU patients, 1.8% received a tracheostomy or were initiated on long-term ventilation; 1,034 received a tracheostomy only, 717 were initiated on invasive ventilation, and 381 were initiated on noninvasive ventilation. Ninety percent had substantial chronic conditions and comorbidities, including more than 50% with moderate or worse cerebral disability upon discharge. Seven percent were initiated after a catastrophic injury/event. Across sites, there was variation in incidence of tracheotomy and initiation of long-term ventilation, ranging from 0% to 4.6%. There also was variation in patient characteristics, time to tracheotomy, number of extubations prior to tracheostomy, and the use of invasive ventilation versus noninvasive ventilation., Conclusions: Although the PICU incidence of initiation of tracheostomies and long-term ventilation was relatively uncommon, it suggests that thousands of children and young adults receive these interventions each year in North American PICUs. The majority of them have conditions and comorbidities that impose on-going care needs, beyond those required by artificial airways and long-term ventilation themselves., Competing Interests: Disclosures: The authors have no potential conflicts of interest to disclose.

Background and Purpose: Detection and treatment of atrial fibrillation is a major goal in secondary stroke prevention. Guidelines recommend at least 24 hours of ECG monitoring after stroke. However, it is unclear how often this is done in routine practice., Methods: In this longitudinal cohort study using data from the Ontario Stroke Registry, we analyzed consecutive patients presenting to designated stroke centers in Ontario, Canada (2003-2013) with a first acute ischemic stroke or transient ischemic attack (TIA) in sinus rhythm and without known atrial fibrillation. The primary outcome was the proportion of patients who received at least 24-hour Holter monitoring within 30 days after stroke/TIA. Secondary analyses assessed total duration of ECG monitoring completed within 90 days after stroke/TIA, temporal trends in monitoring use, and use of Holter monitoring relative to echocardiography., Results: Among 17 398 consecutive eligible patients (mean age 68.8±14.3 years), 30.6% had at least 24 hours of Holter monitoring within 30 days after stroke/TIA. Less than 1% of patients received prolonged monitoring beyond 48 hours. The median time to start monitoring was 9 days poststroke (interquartile range 3-25). Stroke/TIA patients were nearly twice as likely to receive an echocardiogram than a Holter monitor within 90 days (odds ratio 1.8, 95% confidence interval 1.67-2.01)., Conclusions: Less than one third of patients in our cohort received guideline-recommended 24-hour Holter monitoring, and <1% received prolonged ambulatory ECG monitoring. These findings highlight a modifiable evidence-practice gap that likely contributes to an overdiagnosis of strokes as cryptogenic, an underdiagnosis of atrial fibrillation, and missed anticoagulant treatment opportunities for secondary stroke prevention., (© 2016 American Heart Association, Inc.)

Background: Guidelines recommend that patients with stroke or transient ischemic attack (TIA) undergo neuroimaging and cardiac investigations to determine etiology and guide treatment. It is not known how the use of these investigations has changed over time and whether there have been associated changes in management., Objectives: To evaluate temporal trends in the use of brain and vascular imaging, echocardiography, and antithrombotic and surgical therapy after stroke or TIA., Research Design: We analyzed 42,738 patients with stroke or TIA presenting to any of the 11 regional stroke centers in Ontario, Canada between 2003 and 2012 using the Ontario Stroke Registry database. The study period was divided into 1-year intervals and we used the Cochran-Armitage test to determine trends over time., Results: Between 2003/2004 and 2011/2012, the proportion of patients undergoing brain imaging increased from 96% to 99%, as did the proportion receiving ≥3 brain scans (21%-39%), magnetic resonance imaging (13%-50%), vascular imaging (62%-88%), or echocardiography (52%-70%) (P<0.0001 for all comparisons). There was an increase in the proportion receiving any antithrombotic therapy (83%-91%, P<0.0001) but no change in use of anticoagulation (25% overall and 68% in subgroup with atrial fibrillation) or carotid revascularization (1.4%-1.5%, P=0.49)., Conclusions: The use of investigations after stroke has increased over time without concomitant changes in medical or surgical management. Although initial neurovascular imaging is in accordance with practice guidelines, the use of multiple imaging procedures and routine echocardiography are of uncertain clinical effectiveness.

The radiation regulatory scheme in the United States must periodically evolve and adapt to ensure that public health, workers, and the environment are properly protected in view of accepted societal values and the advance of science, technology, and medical practices. Federal regulators must use best judgment in weighing a multitude of factors and considerations. In the early 21st century, a few dependable but tired and antiquated "workhorses" of regulation have been reworked already--but many more remain that likely need reworking. Three primary points of discussion on current directional influences on federal radiation regulation merit examination: • In 2015, what are the stressors driving societal and policy changes and how might these dynamics be forcing reexamination of old regulations? • What are the things that make a "good" regulation and an effective rule? • What are the thorny issues that the federal government is wrestling with and what are some of the notable activities in federal radiation regulations and guidance that are underway? This journal article was presented at the 2015 Annual Meeting of the National Council on Radiation Protection and Measurements and served as a broad overview of federal regulatory actions and issues.

Objectives: To determine the rate of unplanned PICU readmissions, examine the characteristics of index admissions associated with readmission, and compare outcomes of readmissions versus index admissions., Design: Retrospective cohort analysis., Setting: Ninety North American PICUs that participated in the Virtual Pediatric Intensive Care Unit Systems., Patients: One hundred five thousand four hundred thirty-seven admissions between July 2009 and March 2011., Interventions: None., Measurements and Main Results: Unplanned PICU readmission within 48 hours of index discharge was the primary outcome. Summary statistics, bivariate analyses, and mixed-effects logistic regression model with random effects for each hospital were performed.There were 1,161 readmissions (1.2%). The readmission rate varied among PICUs (0-3.3%), and acute respiratory (56%), infectious (35%), neurological (28%), and cardiovascular (20%) diagnoses were often present on readmission. Readmission risk increased in patients with two or more complex chronic conditions (adjusted odds ratio, 1.72; p < 0.001), unscheduled index admission (adjusted odds ratio, 1.37; p < 0.001), and transfer to an intermediate unit (adjusted odds ratio, 1.29; p = 0.004, compared with ward). Trauma patients had a decreased risk of readmission (adjusted odds ratio, 0.67; p = 0.003). Gender, race, insurance, age more than 6 months, perioperative status, and nighttime transfer were not associated with readmission. Compared with index admissions, readmissions had longer median PICU length of stay (3.1 vs 1.7 d, p < 0.001) and higher mortality (4% vs 2.5%, p = 0.002)., Conclusions: Unplanned PICU readmissions were relatively uncommon, but were associated with worse outcomes. Several patient and admission characteristics were associated with readmission. These data help identify high-risk patient groups and inform risk-adjustment for standardized readmission rates.

Objective: To examine the efficacy of cognitive speed of processing training (SOPT) among individuals with Parkinson disease (PD). Moderators of SOPT were also examined., Methods: Eighty-seven adults, 40 years of age or older, with a diagnosis of idiopathic PD in Hoehn & Yahr stages 1-3 and on a stable medication regimen were randomized to either 20 hours of self-administered SOPT (using InSight software) or a no-contact control condition. Participants were assessed at baseline and after 3 months of training (or an equivalent delay). The primary outcome measure was useful field of view test (UFOV) performance, and secondary outcomes included cognitive self-perceptions and depressive symptoms., Results: Results indicated that participants randomized to SOPT experienced significantly greater improvements on UFOV performance relative to controls, Wilks λ = 0.938, F 1,72 = 4.79, p = 0.032, partial η(2) = 0.062. Findings indicated no significant effect of training on secondary outcomes, Wilks λ = 0.987, F2,70 < 1, p = 0.637, partial η(2) = 0.013., Conclusions: Patients with mild to moderate stage PD can self-administer SOPT and improve their cognitive speed of processing, as indexed by UFOV (a robust predictor of driving performance in aging and PD). Further research should establish if persons with PD experience longitudinal benefits of such training and if improvements translate to benefits in functional activities such as driving., Classification of Evidence: This study provides Class III evidence that SOPT improves UFOV performance among persons in the mild to moderate stages of PD.

Objective: To survey pediatric residents' attitudes toward caring for children with severe disabilities., Design: A cross-sectional survey of residents in a university-affiliated pediatric residency program between October and December 2005. Residents were asked to complete a newly designed, 13-item survey. For each item, participants selected the degree to which they did or did not agree with a statement about disabilities or caring for children with severe disabilities., Results: Fifty-five (43%) of 129 eligible residents participated. Eighty-nine percent felt that caring for children with severe disabilities was as rewarding as caring for other children. Ninety-two percent felt that there is a societal responsibility to care for such children; 98% felt families of children with disabilities love their children as much as other families. Two-thirds (66%) admitted frustration related to caring for children who cannot be cured or function independently, and 71% questioned the aggressive treatment of such children. Residents in their second and third postgraduate years were more likely to question the aggressive treatment compared with their junior colleagues., Conclusions: Although pediatric residents had positive attitudes toward children with severe disabilities, emotional and moral tensions did arise around their care.

Purpose: To report the clinical and histopathologic findings of an unusual keratopathy, which may represent a new corneal dystrophy in a patient with Alport syndrome (ATS)., Methods: A 59-year-old woman with longstanding diagnosis of autosomal recessive ATS was evaluated for progressively decreasing vision in the left eye. She had anterior lenticonus and cataract and central corneal stromal opacification with significant thinning and flattening bilaterally. She underwent penetrating keratoplasty and cataract extraction with posterior chamber intraocular lens implantation. We describe the light microscopic and ultrastructural findings from the cornea., Results: Histopathology of the corneal button revealed marked stromal thinning with decreased keratocytes. The endothelial cells were attenuated and focally lost. Immunohistochemical stains for cytokeratin were positive, findings consistent with posterior polymorphous dystrophy (PPMD). Transmission electron microscopy showed necrosis and a marked loss of keratocytes. Multilayering of the endothelium was consistent with PPMD, but mature desmosomes and microvilli were absent. In vivo confocal microscopy on the fellow eye showed linear hyporeflective bands at the level of Descemet's membrane consistent with PPMD. In addition, there were fine linear changes in the deep stroma and diffuse hyperreflectivity of the mid and superficial stroma with lack of identifiable keratocytes throughout., Conclusions: We believe this to be the first reported case to demonstrate some histopathologic features of PPMD in ATS. However, the clinical, histopathologic, and ultrastructural characteristics are not typical of PPMD. This may represent a new phenotypic expression of PPMD or may be a distinct clinicopathologic dystrophy associated with ATS.

Purpose: To report the case of a patient with Fabry disease (FD) whose ocular presentation with chronic chemosis we feel is related to FD and to describe the conjunctival fluorescein angiographic findings., Methods: A 51-year-old male patient with FD on enzyme replacement therapy presented with 1-month chemosis and mild irritation in the left eye. Ocular examination revealed pronounced noninflammatory chemosis inferotemporally in the left eye with conjunctival tortuosity and microaneurysms bilaterally. There was mild corneal verticillata, spoke-like lens opacities, and retinal vascular tortuosity bilaterally, with no evidence of disc or macular edema. Evaluation revealed no systemic cause for his chemosis, including an orbital computerized tomography scan, which showed clear sinuses and no evidence of an intraorbital mass., Results: Conjunctival fluorescein angiography revealed rapid subconjunctival accumulation of dye in the involved eye but failed to demonstrate leakage from tortuous conjunctival vessels or microaneurysms., Conclusions: Although the pathology of chronic chemosis in patients with FD is as yet unknown, we believe that FD should be considered in the differential diagnosis of patients presenting with chronic chemosis of unknown etiology.

Purpose: Driving is a complex behavior that requires the utilization of a wide range of individual abilities. Identifying assessments that not only capture individual differences, but also are related to older adults' driving performance would be beneficial. This investigation examines the relationship between the Useful Field of View (UFOV) assessment and objective measures of retrospective or concurrent driving performance, including state-recorded accidents, on-road driving, and driving simulator performance., Method: The PubMed and PsycINFO databases were searched to retrieve eight studies that reported bivariate relationships between UFOV and these objective driving measures. Cumulative meta-analysis techniques were used to combine the effect sizes in an attempt to determine whether the strength of the relationship was stable across studies and to assess whether a sufficient number of studies have been conducted to validate the relationship between UFOV and driving performance., Results: A within-group homogeneity of effect sizes test revealed that the samples could be thought of as being drawn from the same population, Q [7] = 11.29, p (one-tailed) = 0.13. Therefore, the effect sizes of eight studies were combined for the present cumulative meta-analysis. The weighted mean effect size across the studies revealed a large effect (Cohen's d = 0.945), with poorer UFOV performance associated with negative driving outcomes. This relationship was robust across multiple indices of driving performance and several research laboratories., Conclusions: This convergence of evidence across numerous studies using different methodologies confirms the importance of the UFOV assessment as a valid and reliable index of driving performance and safety. Recent prospective studies have confirmed a relationship between UFOV performance and future crashes, further supporting the use of this instrument as a potential screening measure for at-risk older drivers.

Objectives: To determine if oxyhemoglobin saturation in blood samples taken from the superior vena cava or right atrium can be substituted for oxyhemoglobin saturation in blood taken from the proximal pulmonary artery (SVO2) in patients in shock., Design: Prospective clinical investigation., Setting: Mixed surgical/medical intensive care unit in a university hospital., Patients: Thirty consecutive patients in severe circulatory shock who required insertion of a pulmonary artery flotation catheter (PAFC) immediately on intensive care unit admission. All patients fulfilled the criteria described below which were established in advance., Measurements and Main Results: Oxyhemoglobin saturation in the superior vena cava, right atrium, and pulmonary artery (SVO2) was measured by cooximetry in consecutive blood samples from each site during initial insertion of the PAFC. The mean standard deviation of values from these sites was similar: 74 +/- 12.5%, 70.+/- 13%, and 71.3 +/- 12.7%, respectively. However, when superior vena cava and right atrial oxyhemoglobin saturations and SvO2 were compared, the ranges and 95% confidence limits were found to be clinically unacceptable. The ranges were -19.3 to 23.1% and -19.7 to 16.7%, respectively, and the 95% confidence limits were -18.4 to 24.2% and -18.6 to +17.3%, respectively., Conclusions: These wide range differences and confidence limits would lead to large errors if superior vena cava or right atrial oxyhemoglobin saturations were substituted for true mixed venous blood in oxygen transport or pulmonary venous admixture calculations, or if clinical decision making was based on individual results. In patients in shock in whom clinical decisions may be based on the value of mixed venous oxyhemoglobin, oxyhemoglobin saturation is only reliably measured in samples taken from the pulmonary artery.

Objective: To compare the hemodynamic and oxygen transport responses to a rapid (< 10-min) infusion of 500 mL of modified fluid gelatin (group A) or hydroxyethyl starch (group B) in patients suffering from acute hypovolemia., Design: Prospective, randomized, noncrossover study., Setting: University hospital, general intensive care unit., Patients: Twenty-eight patients with hypovolemia mechanically ventilated for concurrent acute respiratory failure., Interventions: Patients were mechanically ventilated. Pulmonary and femoral artery catheters were used for hemodynamic monitoring., Measurements and Main Results: Hemodynamic and oxygen transport variables were determined at baseline, 15 mins, and 30 mins after the infusion of each fluid. In both groups pulmonary artery occlusion pressure, stroke volume, and cardiac index significantly increased. In neither group did heart rate decrease. Oxygen delivery increased significantly in group A patients but not in group B patients. This result was due to greater hemodilution in group B patients., Conclusions: There are no significant differences in the hemodynamic responses to hydroxyethyl starch or modified fluid gelatin. The hemodynamic and oxygen transport effects of artificial colloid solutions may not be entirely predictable and should be monitored in critically ill patients.

University of Wisconsin (UW) and Eurocollins (EC) solutions are widely used for preservation of organs before transplantation. However, effect of storage solutions on vascular interface for transplant success is not known. In this study, we have used rat aorta as a model and assessed the effects of cold storage in UW and EC solutions on smooth muscle and endothelial function and the morphology. Smooth muscle and endothelial functions of the rat aorta were assessed using in vitro isometric tension measurement. Morphologic studies were done with scanning and transmission electron microscopy. No significant difference in contractile response to either norepinephrine (NE) or potassium chloride was observed between control aorta and aorta stored in UW solution for 1 hr or 24 hr. In contrast, sensitivity, but not the reactivity to NE and KCl, was increased in aorta stored in EC solution for 1 hr. If the tissues were stored in EC solution for 24 hr, both sensitivity and reactivity to NE and KCl were significantly reduced. Relaxatory response to acetylcholine, in endothelium-intact vessels were reduced in aortas stored in EC solution, but not in UW solution. The magnitude of relaxations observed in tissues stored in the EC solution for 24 hr was less than in tissues stored for 1 hr. Sodium nitroprusside elicited similar relaxatory response in endothelium-denuded control tissue and in tissues stored in UW and EC solution. Electron microscopy data revealed marked swelling of the cell, loss of mitochondria and other intracellular organelles, and striking calcium deposits after preservation of the vessels in EC for 1 or 24 hr. In aorta stored in UW solution for 24 hr, endothelial and smooth muscle cells were intact, with moderate-size vacuoles in the cytoplasm. These results suggest that the UW solution is more suitable than EC solution for short-term preoperative storage of blood vessels.

The effects of somatic nociceptive afferent stimulation on aspects of cardiac function and oxygen transport were examined in a model of hemorrhage in anesthetized pigs. The brachial nerves were stimulated (BNS) alternately to obtain a rise in heart rate of 18% and in mean arterial pressure of 17%. This stimulation was started 75 minutes before the start of hemorrhage and maintained throughout and after the withdrawal of blood. The animals were bled at a rate of 0.75 ml/min.kg until a total of 30 ml/kg had been removed. At the end of hemorrhage the reductions in cardiac index (CI), stroke volume (SV), and left ventricular stroke work (LVSW) were greater in the BNS group compared with controls. The nociceptive stimulation also elicited greater reductions in oxygen delivery (DO2I) and oxygen consumption (VO2) and a greater rise in the arterial plasma lactate concentration. Thus it seems that nociceptive stimulation exacerbates the changes in systemic oxygen transport and cardiac function induced by hemorrhage.

Objective: To review clinical studies of oxygen transport in cardiogenic and septic shock., Design: Descriptive and prospective studies., Setting: University hospital multi disciplinary ICU., Patients: Critically ill cardiogenic and septic shock patients greater than 18 and less than 80 yrs of age., Interventions: The responses to volume loading with colloid or crystalloid and infusion of catecholamines are documented with baseline hemodynamic and oxygen transport measurements before and after administration of catecholamines., Measurements and Main Results: Nineteen patients in cardiogenic shock were studied. In three patients, invasive systemic mean arterial pressure was greater than 80 mm Hg and cardiac index was greater than 2.0 L/min.m2. In all patients, there were increases in oxygen extraction ratio that averaged 48 +/- 18 (SD) %. However, in 30 septic shock patients, extraction ratio was 24 +/- 2%. In both groups, the response to therapy was an increase in mixed venous oxygen saturation from 54 +/- 16% to 69 +/- 8% in cardiogenic patients (p less than .001) and from 75 +/- 2% to 80 +/- 1% in septic shock (p less than .01)., Conclusions: There are widely differing oxygen transport patterns in cardiogenic and septic shock that may have implications for therapy.

Objective: To identify any plateau in oxygen consumption (VO2) when oxygen delivery (DO2) is increased in patients with the adult respiratory distress syndrome (ARDS)., Design: Clinical prospective study; multiple regression analysis was done to assess the relationship between VO2 and DO2 for pooled data and for each individual patient., Setting: University hospital ICU., Patients: Twenty consecutive patients aged 18 to 78 yrs (mean 43.5) in whom ARDS was present during their ICU stay., Interventions: Multiple measurements were obtained in individual patients (mean number of measurements 40, range 20 to 83) and mathematical models were fitted to both pooled and individual patient data. DO2 ranged from 212 to 1550 mL/min.m2 with a maximum of 758 to 1550 mL/min.m2 (mean 1136). Because of the large variations between patients, it was not justifiable to describe a relationship for the pooled data and each case was analyzed individually., Measurements and Main Results: We found the optimal regression model to be linear in 13 patients, cubic in four, and either cubic or linear in one. Two patients demonstrated no significant relationship. The relationship for the group was determined from each patient's data and was best described by linear regression., Conclusions: In no patient was there evidence of a plateau, despite high levels of DO2 being achieved in all patients.

Management of shock is generally guided by hemodynamic data, but the true aim of therapy should be optimizing oxygen delivery (DO2) and consumption (VO2). Available data do not support the hypothesis that there is a single critical threshold of DO2 below which tissue hypoxia occurs; thus, DO2 and VO2 should be addressed for each patient. Interventions that raise BP, such as infused catecholamines, may actually decrease DO2, as can mechanical ventilation with PEEP. Therefore, the clinician should avoid responding solely to hemodynamic data and should direct interventions toward delivering the optimum amount of oxygen to the patient's tissues.

The hemodynamic and oxygen transport effects of the rapid infusion of 500 ml of modified fluid gelatin, an artificial colloid widely used in Europe, were studied in a group of critically ill patients suffering from cardiovascular instability. Oxygen consumption tended to increase. There were no significant changes in heart rate, shunt fraction, or systemic vascular resistance index. There were significant increases in mean arterial pressure, pulmonary artery wedge pressure, stroke index, cardiac index, and oxygen delivery. There were significant decreases in Hgb concentration and arterial oxygen content. The overall circulatory effects of modified fluid gelatin are beneficial.

In a heterogeneous group of 23 critically ill patients with recurrent and intractable bouts of supraventricular arrhythmia, increases in pulmonary artery wedge pressure significantly decreased cardiac output and exacerbated respiratory failure. Most patients were eventually stabilized on a long-term iv infusion of the calcium antagonist verapamil which, with appropriate monitoring, was well tolerated. We suggest that the use of verapamil infusion may play a significant role in the management of such patients and that further studies are justified.

Ten patients with severe septic shock were studied. After plasma volume expansion to an optimal pulmonary artery wedge pressure, above which there were no further increases in cardiac index, all patients remained hypotensive and oliguric. The arterial hypotension was unresponsive to increasing doses of dopamine and dobutamine alone and to a fixed combination of both. In all patients studied, infusion of norepinephrine alone reversed the hypotension and increased significantly the mean arterial pressure, systemic vascular resistance and left ventricular stroke work index (p less than .005). There were only minor increases in heart rate. Oxygen transport indices measured in six patients demonstrated variable alterations in oxygen delivery and consumption.

The responses to therapy of 29 patients in septic shock are described. Patients received controlled plasma volume expansion followed by infusions of norepinephrine, dobutamine, and dopamine to achieve appropriate therapeutic goals. Increases in oxygen delivery (Do2) from 605 +/- 40 (SEM) to 843 +/- 27 ml/min-m2 (p less than .001) were associated with increases in oxygen consumption (Vo2) from 130 +/- 6.8 to 169 +/- 6.2 ml/min.m2 (p less than .001). The overall hospital survival rate was 52%. We suggest that the rational use of adrenergic agents and the achievement of appropriate physiologic end-points for therapy not only result in the reversal of hypotension, but also maintain or increase Do2 and Vo2, and may improve survival.

During the treatment of 26 shocked patients, measurements were made of the central blood to peripheral skin temperature gradient. No significant correlation was found between this gradient and cardiac index (CI), or systemic vascular resistance (SVR) or its index (SVRI). There was no significant correlation between the change in gradient and the changes in CI, SVR or SVRI in any single patient. We conclude that it is incorrect to base any judgment of a patient's hemodynamic status on a core/peripheral temperature gradient during shock, and it is irrational to initiate therapy based on this measurement.