International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.

The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development derived from integrating various approaches, including biophysical techniques, structural studies, and translational investigation. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling. SIGNIFICANCE STATEMENT: Nuclear receptors (NRs) are ligand-regulated transcription factors that are critical regulators of myriad physiological processes. NRs serve as receptors for an array of drugs, and in this review, we provide an update on recent research into the roles of these drug targets.

Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB.

Frailty and Determinants of Health Among Older Adults in the United States 2011-2016.

OBJECTIVE: To characterize frailty phenotype in a representative cohort of older Americans and examine determinants of health factors. METHODS: Retrospective analysis of data from 5,553 adults ≥60 years old in the 2011-2016 cross-sectional National Health and Nutrition Examination Survey (NHANES). World Health Organization "Determinants of Health" conceptual model was used to prioritize variables for multinomial logistic regression for the outcome of modified Fried frailty phenotype. RESULTS: 482 participants (9%) were frail and 2432 (44%) prefrail. Four factors were highly associated with frailty: difficulty with ≥1 activity of daily living (77%; OR 24.81 p < 0.01), ≥2 hospitalizations in the previous year (17%, OR 3.94 p < 0.01), having >2 comorbidities (27%; OR 3.33 p < 0.01), and polypharmacy (66%; OR 2.38 p < 0.01). DISCUSSION: A modified Fried frailty assessment incorporating five self-reported criteria may be useful as a rapid nursing screen in low-resource settings. These assessments can streamline nursing care coordination and case management activities, thereby facilitating targeted frailty interventions to support healthy aging in vulnerable populations.

Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020-January 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C. METHODS: Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C. RESULTS: Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C. CONCLUSIONS: Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving.

Mitigating a COVID-19 Outbreak Among Major League Baseball Players - United States, 2020.

Mass gatherings have been implicated in higher rates of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), and many sporting events have been restricted or canceled to limit disease spread (1). Based on current CDC COVID-19 mitigation recommendations related to events and gatherings (2), Major League Baseball (MLB) developed new health and safety protocols before the July 24 start of the 2020 season. In addition, MLB made the decision that games would be played without spectators. Before a three-game series between teams A and B, the Philadelphia Department of Public Health was notified of a team A player with laboratory-confirmed COVID-19; the player was isolated as recommended (2). During the series and the week after, laboratory-confirmed COVID-19 was diagnosed among 19 additional team A players and staff members and one team B staff member. Throughout their potentially infectious periods, some asymptomatic team A players and coaches, who subsequently received positive SARS-CoV-2 test results, engaged in on-field play with teams B and C. No on-field team B or team C players or staff members subsequently received a clinical diagnosis of COVID-19. Certain MLB health and safety protocols, which include frequent diagnostic testing for rapid case identification, isolation of persons with positive test results, quarantine for close contacts, mask wearing, and social distancing, might have limited COVID-19 transmission between teams.

Patient Safety Culture Survey in Pediatric Complex Care Settings: A Factor Analysis.

OBJECTIVES: Children with complex medical needs are increasing in number and demanding the services of pediatric long-term care facilities (pLTC), which require a focus on patient safety culture (PSC). However, no tool to measure PSC has been tested in this unique hybrid acute care-residential setting. The objective of this study was to evaluate the psychometric properties of the Nursing Home Survey on Patient Safety Culture tool slightly modified for use in the pLTC setting. METHODS: Factor analyses were performed on data collected from 239 staff at 3 pLTC in 2012. Items were screened by principal axis factoring, and the original structure was tested using confirmatory factor analysis. Exploratory factor analysis was conducted to identify the best model fit for the pLTC data, and factor reliability was assessed by Cronbach alpha. RESULTS: The extracted, rotated factor solution suggested items in 4 (staffing, nonpunitive response to mistakes, communication openness, and organizational learning) of the original 12 dimensions may not be a good fit for this population. Nevertheless, in the pLTC setting, both the original and the modified factor solutions demonstrated similar reliabilities to the published consistencies of the survey when tested in adult nursing homes and the items factored nearly identically as theorized. CONCLUSIONS: This study demonstrates that the Nursing Home Survey on Patient Safety Culture with minimal modification may be an appropriate instrument to measure PSC in pLTC settings. Additional psychometric testing is recommended to further validate the use of this instrument in this setting, including examining the relationship to safety outcomes. Increased use will yield data for benchmarking purposes across these specialized settings to inform frontline workers and organizational leaders of areas of strength and opportunity for improvement.

Clinical decision support for therapeutic decision-making in cancer: A systematic review.

Cancer management, including supportive care, is complex and requires availability and synthesis of published and patient-specific data to make appropriate therapeutic decisions. Clinical decision support (CDS) may be an effective implementation strategy to support complex decision making although it is unclear whether it improves process outcomes, patient outcomes or both in cancer settings. We therefore conducted a systematic review to identify CDS that have been used to support therapeutic decision making in clinical cancer settings. Outcomes of interest included the effect of CDS on the process, such as clinician's decision making and effect on patient outcomes. Ten studies met inclusion criteria, with variability in the study design, setting, and intervention. Of the nine studies that measured process outcomes, five demonstrated significant improvement; and of the six that measured patient outcomes, four demonstrated significant improvement. All included studies utilized CDS that were informed by clinical practice guidelines. In conclusion, CDS to guide cancer therapeutic decision making is an understudied but promising area. Further research is needed.

Prior antibiotic use and acquisition of multidrug-resistant organisms in hospitalized children: A systematic review.

OBJECTIVE: Multidrug-resistant organisms (MDROs) cause ~5%-10% of infections in hospitalized children, leading to an increased risk of death, prolonged hospitalization, and additional costs. Antibiotic exposure is considered a driving factor of MDRO acquisition; however, consensus regarding the impact of antibiotic factors, especially in children, is lacking. We conducted a systematic review to examine the relationship between antibiotic use and subsequent healthcare-associated infection or colonization with an MDRO in children. DESIGN: Systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. METHODS: We searched PubMed and Embase for all English, peer-reviewed original research studies published before September 2018. Included studies evaluated hospitalized children, antibiotic use as an exposure, and bacterial MDRO as an outcome. RESULTS: Of the 535 studies initially identified, 29 met the inclusion criteria. Overall, a positive association was identified in most studies evaluating a specific antibiotic exposure (17 of 21, 81%), duration of antibiotics (9 of 12, 75%), and number of antibiotics received (2 of 3, 67%). Those studies that evaluated any antibiotic exposure had mixed results (5 of 10, 50%). Study sites, populations, and definitions of antibiotic use and MDROs varied widely. CONCLUSIONS: Published studies evaluating this relationship are limited and are of mixed quality. Limitations include observation bias in recall of antibiotic exposure, variations in case definitions, and lack of evaluation of antibiotic dosing and appropriateness. Additional studies exploring the impact of antibiotic use and MDRO acquisition may be needed to develop effective antibiotic stewardship programs for hospitalized children.

Measuring Quality in Home Healthcare.

BACKGROUND/OBJECTIVES: Improving quality performance in home health is an increasingly high priority. The objective of this study was to examine trends in industry performance over time using three quality measures: a composite quality metric (Q index), an infection prevention measure (vaccination verification), and an outcome measure (hospital avoidance). DESIGN/SETTING/PARTICIPANTS/MEASURES: We linked Home Health Compare and Provider of Services data from 2012 to 2016, which included 39 211 observations during the 5-year study period and 7670 agencies in 2016. The Q index was developed to allow comparability over time, equally weighting the contributions of each element. After examining summary statistics, we developed three regression models stratified by ownership (for-profit/nonprofit agency) and included two constructs of nurse staffing, in addition to controlling for known confounders. RESULTS: Most agencies (80.4%) were for-profit agencies. The Q index and vaccination verification improved substantially over time, but there was no change in hospital avoidance. Ownership status was associated with all three measures (P < .001). Registered nurse staffing (relative to licensed practical nurses and home health aides) was associated with higher Q index and vaccination verification (P < .001). CONCLUSION: The Q index allows for assessment of trends over time in home healthcare. Ownership and nurse staffing are important factors in the quality of care. The overall home care market is driven by for-profit agencies, but their characteristics and outcomes differ from nonprofit agencies. J Am Geriatr Soc 67:1859-1865, 2019.

A prospective, single-center, randomized study to assess whether automated coregistration of optical coherence tomography with angiography can reduce geographic miss.

OBJECTIVE: We sought to evaluate whether automated coregistration of optical coherence tomography (OCT) with angiography reduces geographic miss (GM) during coronary stenting. BACKGROUND: Previous intravascular ultrasound or OCT studies have showed that residual disease at the stent edge or stent edge dissection was associated with stent thrombosis or edge restenosis. This has been termed GM. METHODS: Two hundred de novo coronary lesions were randomized in a 1:1 ratio to OCT-guided percutaneous coronary intervention (PCI) with versus without automated coregistration of OCT with angiography. GM, the primary endpoint, was defined as angiographic ≥type B dissection or diameter stenosis >50% or OCT minimum lumen area <4.0 mm2 with significant residual disease or dissection (dissection flap >60°) within 5 mm from the stent edge. RESULTS: The prevalence of GM was not different comparing OCT-guided PCI with versus without automated coregistration (27.6% vs 34.0%, P = 0.33). However, there was a trend toward a reduced prevalence of significant distal stent edge dissection in lesions with automated coregistration (11.1% vs 20.8%, P = 0.07). The discrepancy in the distance between planned versus actual implanted stent location with automated coregistration was significantly shorter than without coregistration (1.9 ± 1.6 mm vs 2.6 ± 2.7 mm, P = 0.03), especially the prevalence of ≥5 mm discrepancy that was less frequent with automated coregistration. CONCLUSIONS: Automated coregistration of OCT with angiography did not reduce the primary endpoint of GM after stent implantation.

RORγ regulates the NLRP3 inflammasome.

RAR-related orphan receptor γ (RORγ) is a nuclear receptor that plays an essential role in the development of T helper 17 (Th17) cells of the adaptive immune system. The NLRP3 inflammasome is a component of the innate immune system that processes interleukin (IL)-1ß into a mature cytokine. Elevated activity of the NLRP3 inflammasome contributes to the progression of an array of inflammatory diseases. Bone marrow-derived macrophages (BMDMs) isolated from RORγ-null mice displayed reduced capacity to secrete IL-1ß, and they also displayed a reduction in Nlrp3 and Il1b gene expression. Examination of the promoters of the Il1b and Nlrp3 genes revealed multiple putative ROR response elements (ROREs) that were occupied by RORγ. RORγ inverse agonists were effective inhibitors of the inflammasome. RORγ inverse agonists suppressed lipopolysaccharide (LPS)/ATP-stimulated IL-1ß secretion and expression of Il1b and Nlrp3 in BMDMs. Additionally, the ability of the RORγ inverse agonists to suppress IL-1ß secretion was lost in Nlrp3-null macrophages. The potential for targeting the NLRP3 inflammasome in vivo using RORγ inverse agonists was examined in two models: LPS-induced sepsis and fulminant hepatitis. Pharmacological inhibition of RORγ activity reduced plasma IL-1ß as well as IL-1ß production by peritoneal macrophages in a model of LPS-induced sepsis. Additionally, RORγ inverse agonists reduced mortality in an LPS/d-galactosamine-induced fulminant hepatitis mouse model. These results illustrate a major role for RORγ in regulation of innate immunity via modulation of NLRP3 inflammasome activity. Furthermore, these data suggest that inhibiting the NLRP3 inflammasome with RORγ inverse agonists may be an effective method to treat NLRP3-associated diseases.

Perception of Patient Safety Culture in Pediatric Long-Term Care Settings.

INTRODUCTION: Patient safety culture (PSC) is an emerging construct in adult long-term care settings. No measures are validated to quantify PSC in pediatric long-term care (pLTC) settings despite the importance of safety for this vulnerable population. The study purposes are to (1) describe PSC in pLTC, (2) assess the relationship of PSC to facility recommendation and overall safety rating, and (3) test the stability and reliability of the PSC survey over time. METHODS: A modified Nursing Home PSC (NHSPSC) survey was administered to employees at three pLTC facilities over 3 years; data were summarized and compared over time. RESULTS: In all, 208 surveys were completed. Staff perceptions on "feedback and communication about incidents" and "overall perceptions of resident safety" were most positive and associated with responses of recommending the facility and high overall ratings for child safety (p < .05). CONCLUSIONS: The modified NHSPSC survey was reliable by Cronbach alpha and findings were consistent over time in these pLTC settings. This tool may be a useful adjunct to safety initiatives in pLTC. Knowledge derived from this survey can provide actionable information for consumers, pLTC employees, managers, and administrators.

Associations Between Enteral Nutrition and Acute Respiratory Infection Among Patients in New York Metropolitan Region Pediatric Long-Term Care Facilities.

BACKGROUND: Pediatric long-term care facilities (pLTCF) serve a complicated and resource-intensive patient population with high usage of nutrition support. However, the relationship between nutrition support and outcomes among pLTCF residents is not well understood. We described this relationship in three metropolitan New York pLTCF and a subsample of infants from one of these facilities with a feeding disorders unit. METHODS: In this prospective cohort study, we used logistic regression to assess relationships between enteral nutrition (EN), and acute respiratory infections (ARI) among residents (n = 720, 50% male, mean age = 5.5 years, mean number comorbidities = 2.1) and infant subsample (<1 year, n = 208, 50% male, mean number comorbidities = 2.0). We tested these associations in multivariable models controlling for numbers of comorbidities and infections. RESULTS: Many residents received nutrition via percutaneous (59%) or nasogastric (15%) feeding tubes. In univariate analyses, residents receiving EN had more comorbidities. In multivariable analyses, EN was associated with ARI (incidence rate ratio = 1.65, p < .001). Among infants in the specialized unit, greater risk of ARI was associated only with percutaneous (incidence rate ratio = 1.94, p < .01) feeding. EN was associated with lower odds of being discharged home (OR = 0.45, p < .01). CONCLUSION: The prevalence of EN, complexity of cases, and necessity of long-term EN make nutrition support important in pLTCFs. Differences in EN types and adverse outcomes in the infant subsample suggest different care is necessary for this subpopulation. Results provide context for improving quality of care and clinician/caregiver education for this population.

Behavioral Interventions to Reduce Infections in Pediatric Long-term Care Facilities: The Keep It Clean for Kids Trial.

Children in pediatric long-term care facilities (pLTCF) represent a highly vulnerable population and infectious outbreaks occur frequently, resulting in significant morbidity, mortality, and resource use. The purpose of this quasi-experimental trial using time series analysis was to assess the impact of a 4-year theoretically based behavioral intervention on infection prevention practices and clinical outcomes in three pLTCF (288 beds) in New York metropolitan area including 720 residents, ages 1 day to 26 years with mean lengths of stay: 7.9-33.6 months. The 5-pronged behavioral intervention included explicit leadership commitment, active staff participation, work flow assessments, training staff in the World Health Organization "'five moments of hand hygiene (HH)," and electronic monitoring and feedback of HH frequency. Major outcomes were HH frequency, rates of infections, number of hospitalizations associated with infections, and outbreaks. Mean infection rates/1000 patient days ranged from 4.1-10.4 pre-intervention and 2.9-10.0 post-intervention. Mean hospitalizations/1000 patient days ranged from 2.3-9.7 before and 6.4-9.8 after intervention. Number of outbreaks/1000 patient days per study site ranged from 9-24 pre- and 9-18 post-intervention (total = 95); number of cases/outbreak ranged from 97-324 (total cases pre-intervention = 591 and post-intervention = 401). Post-intervention, statistically significant increases in HH trends occurred in one of three sites, reductions in infections in two sites, fewer hospitalizations in all sites, and significant but varied changes in the numbers of outbreaks and cases/outbreak. Modest but inconsistent improvements occurred in clinically relevant outcomes. Sustainable improvements in infection prevention in pLTCF will require culture change; increased staff involvement; explicit administrative support; and meaningful, timely behavioral feedback.

Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities.

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. Main Outcomes and Measures: Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. Results: The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. Conclusions and Relevance: In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population.

Family Communication about End-of-Life Decisions and the Enactment of the Decision-Maker Role.

End-of-life (EOL) decisions in families are complex and emotional sites of family interaction necessitating family members coordinate roles in the EOL decision-making process. How family members in the United States enact the decision-maker role in EOL decision situations was examined through in-depth interviews with 22 individuals who participated in EOL decision-making for a family member. A number of themes emerged from the data with regard to the enactment of the decision-maker role. Families varied in how decision makers enacted the role in relation to collective family input, with consulting, informing and collaborating as different patterns of behavior. Formal family roles along with gender- and age-based roles shaped who took on the decision-maker role. Additionally, both family members and medical professionals facilitated or undermined the decision-maker's role enactment. Understanding the structure and enactment of the decision-maker role in family interaction provides insight into how individuals and/or family members perform the decision-making role within a cultural context that values autonomy and self-determination in combination with collective family action in EOL decision-making.

Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care?

BACKGROUND: Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. METHODS: We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. RESULTS: There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). CONCLUSIONS: Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset.

Impact of Infection Prevention and Control Initiatives on Acute Respiratory Infections in a Pediatric Long-Term Care Facility.

We evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (ARIs) in a pediatric long-term care facility. ARIs did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. Influenza rates decreased significantly. Infect Control Hosp Epidemiol 2016;37:859-862.

Assessing Nursing Care Needs of Children With Complex Medical Conditions: The Nursing-Kids Intensity of Care Survey (N-KICS).

UNLABELLED: Recent medical advances have resulted in increased survival of children with complex medical conditions (CMC), but there are no validated methods to measure their care needs. OBJECTIVES/METHODS: To design and test the Nursing-Kids Intensity of Care Survey (N-KICS) tool and describe intensity of nursing care for children with CMC. RESULTS: The psychometric evaluation confirmed an acceptable standard for reliability and validity and feasibility. Intensity scores were highest for nursing care related to infection control, medication administration, nutrition, diaper changes, hygiene, neurological and respiratory support, and standing program. CONCLUSIONS: Development of a psychometrically sound measure of nursing intensity will help evaluate and plan nursing care for children with CMC.

Direct costs of acute respiratory infections in a pediatric long-term care facility.

Acute respiratory tract infections (ARI) are a major burden in pediatric long-term care. We analyzed the financial impact of ARI in 2012-2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non-respiratory viral season, $31 224 and $3242 per 1000 patient-days, respectively (P < 0·001). ARI are burdensome for pediatric long-term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.