OBJECTIVE\nTo determine the cost-effectiveness and cost-benefit of an infection control program to reduce nosocomial respiratory syncytial virus (RSV) transmission in a large pediatric hospital.\n\n\nDESIGN\nRSV nosocomial infection (NI) was studied for 8 years, before and after intervention with a targeted infection control program. The cost-effectiveness of the intervention was calculated, and cost-benefit was estimated by a case-control comparison.\n\n\nSETTING\nChildren's Hospital of Philadelphia, a 304-bed pediatric hospital.\n\n\nPATIENTS\nAll inpatients with RSV infection, both community- and hospital-acquired.\n\n\nINTERVENTION\nConsisted of early recognition of patients with respiratory symptoms, confirmation of RSV infection by laboratory testing, establishing cohorts of patients and nursing staff, gown and glove barrier precautions, and monitoring and education of staff.\n\n\nOUTCOME MEASURES\nThe incidence density of RSV NI before and after the intervention was calculated as the rate per 1000 patient days-at-risk for infection. Intervention costs included laboratory testing, isolation, and administration of the program. The cost of RSV NI was estimated by comparing hospital charges for 30 cases and matched uninfected controls.\n\n\nRESULTS\nA total of 148 patients acquired NI (88 before and 60 after the intervention). The Mantel-Haenszel stratified relative risk for NI in the period before the infection control program, compared with the postintervention period, was.61 (95% confidence interval:.53-.69). By applying the preintervention stratum-specific rates of infection to the days-at-risk in the postintervention period, an estimated 100 NIs would have been expected, which in comparison to the 60 NIs observed, yielded an estimated program effectiveness of 10 RSV NIs prevented per season. The total cost of the program per season was $15 627 or $1,563/NI prevented. In comparison, the mean cost to the hospital was $9,419/case of RSV NI, resulting in a cost-benefit ratio of 1:6.\n\n\nCONCLUSIONS\nA targeted infection control intervention was cost-effective in reducing the rate of RSV NI. For every dollar spent on the program, approximately $6 was saved.

Nosocomial respiratory syncytial virus infections : The cost-effectiveness and cost-benefit of infection control.

Pre-eclampsia (PE) is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “pre-eclampsia” that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful. PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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A Dormant Microbial Component in the Development of Preeclampsia

BACKGROUND Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). METHODS Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP). RESULTS Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). CONCLUSIONS Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden.

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood

Importance Ocular manifestations and outcomes in children with confirmed coronavirus disease 2019 (COVID-19), relevant affecting factors, and differences in ocular disease between children and adults have yet to be fully understood. Objective To investigate ocular manifestations and clinical characteristics of children with laboratory-confirmed COVID-19. Design, Setting, and Participants This cross-sectional study was conducted at Wuhan Children’s Hospital in Wuhan, China. Children with COVID-19 confirmed by severe acute respiratory syndrome coronavirus disease 2 nucleic acid tests of upper respiratory tract specimens between January 26 and March 18, 2020, were included. Main Outcomes and Measures Onset clinical symptoms and duration, ocular symptoms, and needs for medication. Results A total of 216 pediatric patients were included, among whom 134 (62%) were boys, with a median (interquartile range) age of 7.25 (2.6-11.6) years. Based on the exposure history, 193 children (89.4%) had a confirmed (173 [80.1%]) or suspected (20 [9.3%]) family member with COVID-19 infection. The most common symptoms among symptomatic children were fever (81 [37.5%]) and cough (79 [36.6%]). Of 216 children, 93 (43.1%) had no systemic or respiratory symptoms. All children with mild (101 [46.8%]) or moderate (115 [53.2%]) symptoms recovered without reported death. Forty-nine children (22.7%) showed various ocular manifestations, of which 9 had ocular complaints being the initial manifestations of COVID-19. The common ocular manifestations were conjunctival discharge (27 [55.1%]), eye rubbing (19 [38.8%]), and conjunctival congestion (5 [10.2%]). Children with systemic symptoms (29.3% vs 14.0%; difference, 15.3%; 95% CI, 9.8%-20.7%;P = .008) or with cough (31.6% vs 17.5%; difference, 14.1%; 95% CI, 8.0%-20.3%;P = .02) were more likely to develop ocular symptoms. Ocular symptoms were typically mild, and children recovered or improved. Conclusions and Relevance In this cross-sectional study, children hospitalized with COVID-19 in Wuhan, China, presented with a series of onset symptoms including fever, cough, and ocular manifestations, such as conjunctival discharge, eye rubbing, and conjunctival congestion. Patients’ systemic clinical symptoms or cough were associated with ocular symptoms. Ocular symptoms recovered or improved eventually.

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Ocular Manifestations and Clinical Characteristics of Children With Laboratory-Confirmed COVID-19 in Wuhan, China.

http://www.journalofinfection.com/article/S0163445322005576/pdf

Efficacy and safety of Paxlovid for COVID-19:a meta-analysis

Enhanced level of soluble urokinase plasminogen activator receptor (suPAR) level has been associated with activation of the immune system. It may be a novel biomarker for pneumonia severity, yet data on this subject are limited. In the present study we seek to determine the suPAR level in hospitalized children with community-acquired pneumonia (CAP), its correlation with pneumonia severity, and to compare the suPAR level between pneumonia and healthy conditions. The study encompassed a total of 596 children: 447 with pneumonia and 119 healthy. suPAR was measured in 227 out of the 447 pneumonia patients and in all healthy subjects. We used clinical indicators (fever, time for defeverscence, heart and breath rate, saturation, and length of antibiotic treatment and of hospitalization) and laboratory indicators (CRP, procalcitonin, white blood cell count, and sodium) to assess the CAP severity. The finding were that the suPAR concentration in children with pneumonia was significantly higher (median 7.11 ng/mL) than in healthy individuals (4.68 ng/mL). We found a positive correlation between the suPAR and the following factors: fever, time for defeverscence, length of hospital stay, and elevated CRP and procalcitonin levels. There was a reverse correlation with sodium concentration and capillary blood saturation. Moreover, the suPAR level was significantly higher in children with a severe course of pneumonia compared with those having non-severe pneumonia (7.79 vs. 6.87 ng/mL; p = 0.006). In conclusion, suPAR elevation is observed in pneumonia and may reflect its severity.

Soluble Urokinase Plasminogen Activator Receptor: An Indicator of Pneumonia Severity in Children

Respiratory syncytial virus (RSV) contributes significantly to pediatric hospitalizations. An association between air pollution and an increased number of RSV cases has been suggested. We sought to evaluate the short-term impact of air pollutants on RSV hospitalizations in Polish children in the period 2010–2019. Daily concentrations of PM10 and PM2.5 (particulate matter with an aerodynamic diameter less than or equal to 10 μm and 2.5 μm, respectively) and nitrogen dioxide (NO2) were analyzed in general regression models (GRM) to establish their influence and full interaction scheme. Significant seasonal and annual periodicity among 53,221 hospitalizations was observed; finally, data from the 2012–2019 RSV high-risk seasons created models for seven agglomerations. The addition of PM2.5, PM10, and NO2 to the basic model for RSV seasonality explained 23% (4.9–31%, univariate model) to 31.4% (8.4–31%, multivariate model) of the variance in RSV hospitalizations. A 10 μg/m3 increase in PM2.5, PM10, and NO2 concentrations was associated with 0.134 (0.087–0.16), 0.097 (0.031–0.087), and 0.212 (0.04–0.29) average increases in hospitalizations, respectively. In the multivariate models, PM2.5, PM10, and NO2 alone, as well as PM2.5–NO2, PM2.5–PM10, and PM10–NO2 interactions, were associated with hospitalizations in some of the locations, while the metaregression showed statistically significant interactions between each of the pollutants, and between the pollutants and the year of the study. The inclusion of PM2.5, PM10, and NO2 in GRM explains a significant number of RSV hospitalizations. The pollutants act alone and interact together in a varied manner. Reducing air contamination might decrease the costs of hospital healthcare.

Air Pollutants’ Concentrations Are Associated with Increased Number of RSV Hospitalizations in Polish Children

Copeptin has been associated with the severity of pneumonia and its complications. This study was designed to assess the usefulness of copeptin measurement in children with community-acquired pneumonia (CAP) and copeptin’s relation with disease severity and sodium equilibrium. The study encompassed 311 patients (227 with pneumonia and 84 healthy controls) aged 8 days–18 years. Clinical findings and inflammatory markers were used to predict the disease severity. We found that the level of copeptin was significantly higher in patients with CAP (median 0.88 ng/mL) vs. healthy children (0.33 ng/mL; p < 0.01). ROC analysis showed a high AUC value (0.87) and the cut-off point for plasma copeptin level was 0.44 ng/mL, with a high sensitivity (89 %) and specificity (73 %) in recognizing pneumonia. Patients with higher copeptin concentrations were at higher risk of hyponatremia (OR 2.43). Yet there was only a weak reverse correlation between the sodium and the copeptin concentrations (Spearmann’s rank coefficient = −0.19). The levels of copeptin were higher in hyponatremic patients (0.83 ng/mL) vs. normonatremic patients (0.69 ng/mL; p = 0.02). Copeptin elevation did not reflect the CAP severity measured with traditionally used methods. In conclusion, copeptin elevation is a promising marker of pneumonia, but it reflects neither the disease severity nor sodium concentration.

Sodium and copeptin levels in children with community acquired pneumonia.

Community-acquired pneumonia (CAP) is a leading single cause of mortality in children under 5 years of age. In search of new diagnostic markers, soluble urokinase plasminogen activator receptor (suPAR) seems to offer promise as a novel clinical tool. The goal of the present study was to assess the relation between suPAR and the severity of CAP. suPAR was measured in 74 (39 males, 35 females) patients aged from 1 month to about 15 years. Correlation between the level of suPAR and inflammatory markers (white blood cell, neutrophil count, C-reactive protein-CRP, and procalcitonin-PCT) was assessed by Spearmann’s rank coefficient. We found that the median suPAR level in children with pneumonia was 8.29 ng/mL (range 2.44–18.31 ng/mL). In the multivariate logit model, age and CRP level were statistically important. The older children (age above the median value) had higher suPAR (above the median value) less frequently than the younger children (OR = 0.31), whereas the children with greater CRP values (above the median value) had higher suPAR levels than the children with lower CRP concentration (under the median value) (OR = 4.54). There was also a positive correlation between suPAR and PCT levels. In conclusion, we demonstrate a positive correlation between serum suPAR and the non-specific inflammatory markers CRP and PCT in the community acquired pneumonia in children.

Soluble receptor for urokinase plasminogen activator in community-acquired pneumonia in children.

Viral testing is not always recommended in children with bronchiolitis due to doubts concerning its prognostic use. In this retrospective study, we investigated how the RSV testing would influence the frequency of nosocomial infections (NI). The files of 305 children, hospitalized due to the respiratory syncytial virus (RSV) infection in the period 2010–2014, were reviewed in the study. We found ten cases of NI. The RSV preventive measures did not vary in the consecutive years investigated, but the number of viral tests substantially varied. In 2010, 2012, and 2014, when ca. 2 tests per RSV(+) patient were performed, the risk of NI per patient was 1.3%, while in 2011 and 2013, when the RSV testing was less frequent, the accumulated risk per patient was 5.2%. There was a strong adverse relationship between the number of tests performed and the number of NI (rho = −0.975). The children with NI, when compared to those without NI, required a longer hospital stay, generating higher hospital costs regarding treatment, productivity loss, and indirect costs. The expenditure for RSV testing in the years of a low NI risk was higher than that in the high-risk years. Conversely, the expenditure related to NI management was lower in the years of a low NI risk. Each euro spent on RSV testing saved over 26 € from the NI management expenditure. We conclude that RSV testing is needed in the hospital setting to isolate the infected children and to prevent nosocomial RSV spread. This strategy is health advantageous and requires less resources than NI treatment.

August Wrotek

Papers

Soluble Urokinase Plasminogen Activator Receptor: An Indicator of Pneumonia Severity in Children

Air Pollutants’ Concentrations Are Associated with Increased Number of RSV Hospitalizations in Polish Children

Sodium and copeptin levels in children with community acquired pneumonia.

Soluble receptor for urokinase plasminogen activator in community-acquired pneumonia in children.

Nosocomial Infections in Patients Hospitalized with Respiratory Syncytial Virus: A Practice Review.