Change in Functional Status During Hospital Admission and Long-Term Health-Related Quality of Life Among Pediatric Septic Shock Survivors.

OBJECTIVES: To investigate whether change in functional status from pre-hospitalization baseline to hospital discharge is associated with long-term health-related quality of life (HRQL) among children surviving septic shock. DESIGN: Secondary analysis of Life After Pediatric Sepsis Evaluation (LAPSE), a prospective cohort study of children with community-acquired septic shock, enrolled from January 2014 to June 2017. SETTING: Twelve U.S. academic PICUs. PATIENTS: Children, 1 month to 18 years, who survived to hospital discharge and had follow-up data for HRQL at 3 and/or 12 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional Status Scale (FSS) was assessed around enrollment to ascertain baseline status (pre-hospitalization) and at 28 days or hospital discharge. Two measures of HRQL were utilized: children with significant development delay were measured with the Functional Status II-R (FSII-R); typically, developing children were measured with the Pediatric Quality of Life Inventory (PedsQL). Each group was analyzed separately with multivariable regression modeling to determine the association between change in FSS from baseline to day 28 and HRQL at 3 and 12 months from PICU admission. Of the original 389 LAPSE participants, 224 (58%) are included. Among children with developmental delay ( n = 88), worsened FSS was associated with lower FSII-R at 3 months from PICU admission (-2.02; 95% CI, -3.34 to -0.0.71; p = 0.003), but not 12 months. Among developmentally typical children ( n = 136), worsened FSS was associated with lower PedsQL at both 3 and 12 months. Developmentally typical children with a neurologic insult during the PICU stay had the largest decrement in PedsQL at 12 months (-14.04 mo; 95% CI, -22.15 to -5.94 mo; p < 0.001). However, worsened FSS remained associated with poor HRQL-PedsQL at 3 and 12 months, after controlling for neurologic events (both p < 0.001). CONCLUSIONS: Change in FSS during hospitalization for septic shock is associated with long-term reductions in HRQL and could serve as a useful tool for identifying children at risk for this sequela.

Pediatric Septic Shock Care Pathways in General Emergency Departments: A Qualitative Study Targeting How to Really Make it Work.

OBJECTIVES: Many academic pediatric emergency departments (PEDs) have successfully implemented pediatric septic shock care pathways. However, many general emergency departments (GEDs), who see the majority of pediatric ED visits, have not. This study aims to compare the workflow, resources, communication, and decision making across these 2 settings to inform the future implementation of a standardized care pathway for children with septic shock in the GED. METHODS: We used the critical incident technique to conduct semistructured interviews with 24 ED physicians, nurses, and technicians at one PED and 2 GEDs regarding pediatric septic shock care. We performed a thematic analysis using the Framework Method to develop our coding schema through inductive and deductive analyses. We continued an iterative process of revising the schema until we reached consensus agreement and thematic saturation. RESULTS: We identified the following 6 themes: (1) functioning like a "well-oiled machine" may be key to high performance; (2) experiencing the sequence of care for children with sepsis as invariant and predictable may be essential to high-quality performance; (3) resilience and flexibility are characteristic of high levels of performance; (4) believing that "the buck stops here" may contribute to more accountability; (5) continuous system learning is essential; and (6) computerized clinical decision support may not be optimized to drive decision-making at the point of care. Commentary from GED and PED participants differed across the 6 themes, providing insight into the approach for standardized care pathway implementation in GEDs. CONCLUSIONS: Pediatric septic shock workflow, decision making, and system performance differ between the PED and GEDs. Implementation of a standardized care pathway in GEDs will require a tailored approach. Specific recommendations include (1) improving shared situation awareness; (2) simulation for knowledge, skill, and team-based training; and (3) promoting a culture of continuous learning.

Cardiovascular events and risk in patients with systemic lupus erythematosus: Systematic literature review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that typically affects women aged 16-55 years. Cardiovascular disease (CVD) is a well-recognized complication of SLE. This systematic literature review and meta-analysis evaluated the relative risk (RR; compared with non-SLE controls), absolute risk (AR; as incidence proportion, n/N), and incidence rate (IR) of CVD events (including stroke, myocardial infarction [MI], and CVD [composite or undefined]) in adult patients with SLE. The RR of CV risk factors (including hypertension, diabetes, and metabolic syndrome [MetS]) was also examined. METHODS: PubMed and Embase were searched on September 10, 2020. Observational studies published between January 2010 and September 2020 that reported RR, AR, and/or IR of CVD events, or RR of CV risk factors, were eligible. Pooled risk estimates were calculated using a random-effects model. RESULTS: Forty-six studies (16 cross-sectional, 15 retrospective cohort, 14 prospective cohort, and 1 case-control) were included in meta-analyses. Most studies were considered high quality (Critical Appraisal Skills Programme checklists). Compared with adults without SLE, patients with SLE had statistically significantly higher RRs (95% CIs) of stroke (2.51 [2.03-3.10]; 12 studies), MI (2.92 [2.45-3.48]; 11 studies), CVD (2.24 [1.94-2.59]; 8 studies), and hypertension (2.70 [1.48-4.92]; 7 studies). RRs of diabetes (1.24 [0.78-1.96]; 3 studies) and MetS (1.49 [0.95-2.33]; 7 studies) were elevated but not significant. RRs of stroke and MI were generally higher in younger versus older patients with SLE. In patients with SLE, the pooled estimate of AR (95% CI) was 0.03 (0.02-0.05), 0.01 (0.00-0.02), and 0.06 (0.03-0.10) for stroke (7 studies), MI (6 studies), and CVD (8 studies), respectively. The pooled estimate of IR per 1000 person-years (95% CI) was 4.72 (3.35-6.32), 2.81 (1.61-4.32), and 11.21 (8.48-14.32) for stroke (10 studies), MI (6 studies), and CVD (8 studies), respectively. Although heterogeneity (based on I2 value) was high in most analyses, sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSIONS: This meta-analysis found an increased risk of stroke, MI, CVD, and hypertension in patients with SLE compared with the general population, despite substantial heterogeneity across the included studies.

Systematic Literature Review and Meta-analysis of Venous Thromboembolism Events in Systemic Lupus Erythematosus.

The objective of this work was to conduct a systematic literature review (SLR) and meta-analysis (MA) to evaluate the relative risk (RR) of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients with systemic lupus erythematosus (SLE) compared with patients without SLE, as well as the absolute risk (AR) (measured by incidence proportion) and incidence rate (IR) of VTE events in patients with SLE. The SLR was conducted using Embase, MEDLINE, and MEDLINE In-Process to identify observational studies evaluating the risk of VTE, DVT, and PE events in adult patients with SLE compared with the general population, published January 2000 to September 2020. Random-effects models were used as the primary approach in the MA. Heterogeneity was assessed on the basis of the I2 value. Sensitivity analyses were performed to assess the robustness of results to various conditions, and subgroup analysis was performed for the AR of VTE by antiphospholipid status (aPLs) and antiphospholipid syndrome (APS). Of the 50 publications included for data extraction, 44 contained data for consideration in the MA of any one of the measures of interest (RR, AR, or IR) for VTE, DVT, or PE. The pooled RR indicates statistically significantly higher risk of VTE (RR 4.38, 95% confidence interval 2.63-7.29) in patients with SLE compared with the general population. Considerable heterogeneity was present in nearly all MA (I2 = 75-100%). Moreover, a higher pooled AR of VTE was estimated in patients with SLE with aPLs (n/N = 0.13) and APS (n/N = 0.63) compared with patients with SLE without aPLs/APS (n/N = 0.07). Overall, there was evidence of an increased risk of VTE, DVT, and PE in patients with SLE compared with the general population.

Characteristics and Outcomes of Sepsis Presenting in Inpatient Pediatric Settings.

OBJECTIVE: The pediatric sepsis literature lacks studies examining the inpatient setting, yet sepsis remains a leading cause of death in children's hospitals. More information is needed about sepsis arising in patients already hospitalized to improve morbidity and mortality outcomes. This study describes the clinical characteristics, process measures, and outcomes of inpatient sepsis cases compared with emergency department (ED) sepsis cases within the Improving Pediatric Sepsis Outcomes data registry from 46 hospitals that care for children. METHODS: This retrospective cohort study included Improving Pediatric Sepsis Outcomes sepsis cases from January 2017 to December 2019 with onset in inpatient or ED. We used descriptive statistics to compare inpatient and ED sepsis metrics and describe inpatient sepsis outcomes. RESULTS: The cohort included 26 855 cases; 8.4% were inpatient and 91.6% were ED. Inpatient cases had higher sepsis-attributable mortality (2.0% vs 1.4%, P = .025), longer length of stay after sepsis recognition (9 vs 5 days, P <.001), more intensive care admissions (57.6% vs 54.1%, P = .002), and greater average vasopressor use (18.0% vs 13.6%, P <.001) compared with ED. In the inpatient cohort, >40% of cases had a time from arrival to recognition within 12 hours. In 21% of cases, this time was >96 hours. Improved adherence to sepsis treatment bundles over time was associated with improved 30-day sepsis-attributable mortality for inpatients with sepsis. CONCLUSIONS: Inpatient sepsis cases had longer lengths of stay, more need for intensive care, and higher vasopressor use. Sepsis-attributable mortality was significantly higher in inpatient cases compared with ED cases and improved with improved sepsis bundle adherence.

Treatment Patterns and Clinical Characteristics of Patients with Systemic Lupus Erythematosus and Musculoskeletal Symptoms: A Retrospective, Observational Study.

INTRODUCTION: Musculoskeletal (MSK) symptoms, including arthritis and arthralgia, are common manifestations of systemic lupus erythematosus (SLE); definitions of activity patterns in SLE differ across studies. This study described clinical characteristics and treatment patterns of patients with SLE-MSK over time and by disease activity patterns from a real-world setting. METHODS: This retrospective descriptive analysis includes a subset of patients with SLE from the Hopkins Lupus Cohort with identified MSK involvement by scores on the arthritis domain of the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) or Lupus Activity Index. Clinical characteristics and treatment patterns were described for patients with at least two visits over the observation period (2010-2019) for the SLE-MSK population based on three disease activity patterns: chronically active (MSK-CA), relapsing-remitting (MSK-RR), and long quiescence (MSK-LQ). RESULTS: The SLE-MSK subpopulation included 664 patients (4069 person-years). The most frequently used medications over the observation period were antimalarials (95%), corticosteroids (92%), immunosuppressants (58%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (48%); 7% of patients used biologics. The highest use of corticosteroids was in the MSK-CA group (90.5% of follow-up time), followed by MSK- RR (83.9%), and MSK-LQ (46.5%). Mean prednisone dose was significantly higher in MSK-RR (8.5 mg) compared to MSK-CA (6.5 mg). CONCLUSIONS: This descriptive analysis highlights the impact of prevalent manifestations such as arthritis on the chronic use of corticosteroids, immunosuppressants, and NSAIDs to manage disease activity in patients with SLE, suggesting there is a need for new therapeutic options that enable a lower use of medication when treating lupus.

Medication and Fluid Management of Pediatric Sepsis and Septic Shock.

Sepsis is a life-threatening response to infection that contributes significantly to neonatal and pediatric morbidity and mortality worldwide. The key tenets of care include early recognition of potential sepsis, rapid intervention with appropriate fluids to restore adequate tissue perfusion, and empiric antibiotics to cover likely pathogens. Vasoactive/inotropic agents are recommended if tissue perfusion and hemodynamics are inadequate following initial fluid resuscitation. Several adjunctive therapies have been suggested with theoretical benefit, though definitive recommendations are not yet supported by research reports. This review focuses on the recommendations for medication and fluid management of pediatric sepsis and septic shock, highlighting issues related to antibiotic choices and antimicrobial stewardship, selection of intravenous fluids for resuscitation, and selection and use of vasoactive/inotropic medications. Controversy remains regarding resuscitation fluid volume and type, antibiotic choices depending upon infectious risks in the patient's community, and adjunctive therapies such as vitamin C, corticosteroids, intravenous immunoglobulin, and methylene blue. We include best practice recommendations based on international guidelines, a review of primary literature, and a discussion of ongoing clinical trials and the nuances of therapeutic choices.

Association Between Rapid Response Algorithms and Clinical Outcomes of Hospitalized Children.

OBJECTIVES: To evaluate whether the implementation of clinical pathways, known as pediatric rapid response algorithms, within an existing rapid response system was associated with an improvement in clinical outcomes of hospitalized children. METHODS: We retrospectively identified patients admitted to the PICU as unplanned transfers from the general medical and surgical floors at a single, freestanding children's hospital between July 1, 2017, and January 31, 2020. We examined the impact of the algorithms on the rate of critical deterioration events. We used multivariable Poisson regression and an interrupted time series analysis to measure 2 possible types of change: an immediate implementation effect and an outcome trajectory over time. RESULTS: We identified 892 patients (median age: 4 [interquartile range: 1-12] years): 615 in the preimplementation group, and 277 in the postimplementation group. Algorithm implementation was not associated with an immediate change in the rate of critical deterioration events but was associated with a downward rate trajectory over time and a postimplementation trajectory that was significantly less than the preimplementation trajectory (trajectory difference of -0.28 events per 1000 non-ICU patient days per month; 95% confidence interval -0.40 to -0.16; P < .001). CONCLUSIONS: Algorithm implementation was associated with a decrease in the rate of critical deterioration events. Because of the study's observational nature, this association may have been driven by unmeasured confounding factors and the chosen implementation point. Nevertheless, the results are a promising start for future research into how clinical pathways within a rapid response system can improve care of hospitalized patients.

Best practices in pediatric sepsis: building and sustaining an evidence-based pediatric sepsis quality improvement program.

Pediatric sepsis is a common problem worldwide and is associated with significant morbidity and mortality. Best practice recommendations have been published by both the American College of Critical Care Medicine and the Surviving Sepsis Campaign to guide the recognition and treatment of pediatric sepsis. However, implementation of these recommendations can be challenging due to the complexity of the care required and intensity of resources needed to successfully implement programs. This paper outlines the experience with implementation of a pediatric sepsis quality improvement program at Primary Children's Hospital, a free-standing, quaternary care children's hospital in Salt Lake City. The hospital has implemented sepsis projects across multiple care settings. Challenges, lessons learned, and suggestions for implementation are described.PLAIN LANGUAGE SUMMARYSepsis is a life-threatening condition that results from an inappropriate response to an infection by the body's immune system. All children are potentially susceptible to sepsis, with nearly 8,000 children dying from the disease in the US each year. Sepsis is a complicated disease, and several international groups have published guidelines to help hospital teams treat children with sepsis appropriately. However, because recognizing and treating sepsis in children is challenging and takes a coordinated effort from many different types of healthcare team members, following the international sepsis guidelines effectively can be difficult and resource intensive. This paper describes how one children's hospital (Primary Children's Hospital in Salt Lake City, Utah) approached the challenge of implementing pediatric sepsis guidelines, some lessons learned from their experience, and suggestions for others interested in implementing sepsis guidelines for children.

Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. METHODS: Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. RESULTS: Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1-3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient's preferences regarding the importance of these PROs were stable over time. CONCLUSION: The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

Systematic Literature Review of Residual Symptoms and an Unmet Need in Patients With Rheumatoid Arthritis.

OBJECTIVE: To evaluate the nature and burden of residual disease in rheumatoid arthritis (RA) in patients who meet treatment targets. Second, for those who did not meet targets, to evaluate how much is due to patient symptoms. METHODS: Prospective and retrospective studies were searched in Medline, Embase, and Cochrane Library in the English language from January 1, 2008 to April 18, 2018; conference abstracts (from January 2016 to April 2018) and reference lists of relevant studies were also screened. RESULTS: Of 8,339 records identified, 55 were included in the review; 53 were unique studies, including 10 randomized controlled trials. Of these, 48 reported on patients who achieved low disease activity (LDA) or remission. Studies varied in population, treatment goals, and outcome reporting. The proportions of patients with residual symptoms in these studies varied by the definitions used for LDA or remission and were more often reported in patients with LDA than those in remission. The most commonly reported outcome measures were functional disability (n = 34 studies), tender or swollen joints (n = 18), pain (n = 17), patient global assessment (n = 15), and fatigue (n = 14). However, few studies reported the percentage of patients achieving a specific threshold, which could then be used to easily define the presence of residual symptoms. CONCLUSION: Residual symptoms are present in some patients despite their achieving LDA or remission, highlighting an unmet need, especially with respect to improving pain, fatigue, and function. Standardized reporting in future observational studies would facilitate better understanding of this issue in defined RA populations.

Risk Factors for Mortality in Refractory Pediatric Septic Shock Supported with Extracorporeal Life Support.

Risk factors for mortality in children with refractory pediatric septic shock who are supported with extracorporeal life support (ECLS) are largely unknown. Therefore, we performed univariable and multivariable analyses to determine risk factors for mortality among children (<19 years) who underwent an ECLS run between January 2012 and September 2014 at eight tertiary pediatric hospitals, and who had septic shock based on 2005 International Consensus Criteria. Of the 514 children treated with ECLS during the study period, 70 were identified with septic shock. The mortality rate was similar between those with (54.3%) and without septic shock (43.7%). Among those with septic shock, significant risk factors for mortality included cardiac failure or extracorporeal cardiopulmonary resuscitation (ECPR) as indication for ECLS cannulation compared with respiratory failure (P = 0.003), having a new neurologic event following cannulation (P = 0.032), acquiring a new infection following cannulation (P = 0.005), inability to normalize pH in the 48 hours following ECLS cannulation (P = 0.010), and requiring higher daily volume of platelet transfusions (P = 0.005). These findings can be used to help guide clinical decision making for children with septic shock that is refractory to medical management.

Antibiotic Timing in Pediatric Septic Shock.

BACKGROUND AND OBJECTIVES: National guidelines advocate for the administration of antibiotics within 1 hour to children with septic shock, although there is variance in the pediatric evidence-based literature supporting this benchmark. Our objective for this study was to describe the association of target time to antibiotic administration (TTAA) with outcomes of children treated for suspected septic shock in a pediatric emergency department. Septic shock is suspected when signs of perfusion and/or hypotension are present. The primary outcome was mortality. Secondary outcomes included PICU admission, hospital and PICU length of stay, and organ dysfunction resolution by hospital day 2. METHODS: We conducted a retrospective study of children <18 years of age admitted from the pediatric emergency department and treated for suspected septic shock between February 1, 2007, and December 31, 2015. Associations between TTAA and outcomes were evaluated by using multivariable linear and logistic regression models obtained from stepwise selection. RESULTS: Of 1377 patients, 47% were boys with a median age of 4.0 (interquartile range 1.4-11.6) years, 1.5% (20) died, 90% were compliant with TTAA goals, 40% required PICU admission, 38% had ≥2 unique complex chronic conditions, 71% received antibiotics in ≤2 hours, and 30% had a culture-positive bacterial etiology. There were no significant associations between TTAA and outcomes. CONCLUSIONS: We found no association with TTAA and any clinical outcomes, adding to the growing body of literature questioning the timing benchmark of antibiotic administration. Although the importance of antibiotics is not in question, elucidating the target TTAA may improve resource use and decrease inappropriate or unnecessary antibiotic exposure.

Severe Sepsis-Associated Morbidity and Mortality among Critically Ill Children with Cancer.

Severe sepsis (SS) in pediatric oncology patients is a leading cause of morbidity and mortality. We investigated the incidence of and risk factors for morbidity and mortality among children diagnosed with cancer from 2008 to 2012, and admitted with SS during the 3 years following cancer diagnosis. A total of 1,002 children with cancer were included, 8% of whom required pediatric intensive care unit (PICU) admission with SS. Death and/or multiple organ dysfunction syndrome occurred in 34 out of 99 PICU encounters (34%). Lactate level and history of stem-cell transplantation were significantly associated with the development of death and/or organ dysfunction ( p < 0.05).

Variation in Adolescent Idiopathic Scoliosis Surgery: Implications for Improving Healthcare Value.

OBJECTIVES: To investigate the variation in care and cost of spinal fusion for adolescent idiopathic scoliosis (AIS), and to identify opportunities for improving healthcare value. STUDY DESIGN: Retrospective cohort study from the Pediatric Health Information Systems database, including children 11-18 years of age with AIS who underwent spinal fusion surgery between 2004 and 2015. Multivariable regression was used to evaluate the relationships between hospital cost, patient outcomes, and resource use. RESULTS: There were 16 992 cases of AIS surgery identified. There was marked variation across hospitals in rates of intensive care unit admission (0.5%-99.2%), blood transfusions (0%-100%), surgical complications (1.8%-32.3%), and total hospital costs ($31 278-$90 379). Hospital cost was 32% higher at hospitals that most frequently admitted patients to the intensive care unit (P = .009), and 8% higher for each additional 25 operative cases per hospital (P = .003). Hospital duration of stay was shorter for patients admitted to hospitals with highest intensive care unit admission rates and higher surgical volumes. There was no association between cost and duration of stay, 30-day readmission, or surgical complications. The largest contribution to hospital charges was supplies (55%). Review of a single hospital's detailed cost accounting system also found supplies to be the greatest single contributor to cost, the majority of which were for spinal implants, accounting for 39% of total hospital costs. CONCLUSIONS: The greatest contribution to AIS surgery cost was supplies, the majority of which is likely attributed to spinal implant costs. Opportunities for improving healthcare value should focus on controlling costs of spinal instrumentation, and improving quality of care with standardized treatment protocols.