Maternal Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Otherwise Healthy Preterm and Term Infants: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVE: To date, there is no published, formal assessment of all maternal risk factors for respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) in infants. A systematic literature review and meta-analysis were undertaken to ascertain: What maternal risk factors are associated with an increased risk of RSV-LRTI in infants? METHODS: The systematic literature review used explicit methods to identify, select and analyze relevant data. PubMed, Embase and the Cochrane Library were searched (November 2022) using terms regarding: (1) RSV/LRTI; (2) risk factors; (3) pregnant/postpartum population. Bayesian meta-analysis compared RSV hospitalization (RSVH) risk in infants born to mothers with or without certain risk factors. RESULTS: A total of 2353 citations were assessed and 20 were included in the final review (10 individual studies; 10 pooled analyses). In 10 studies examining infants (<1 year) without comorbidities (primary outcome), 10 maternal risk factors were associated with RSV-LRTI/RSVH in multivariate analyses. Meta-analysis revealed smoking while pregnant increased infant RSVH risk by 2.01 (95% credible interval: 1.52-2.64) times, while breast-feeding was protective (0.73, 95% credible interval: 0.58-0.90). Risk scoring tools have reported that maternal risk factors contribute between 9% and 21% of an infant's total risk score for RSVH. CONCLUSIONS: A greater understanding of maternal risk factors and their relative contribution to infant RSV-LRTI will enable more accurate assessments of the impact of preventive strategies.

Understanding Policy Decisions and Their Implications Regarding Preventive Interventions for Respiratory Syncytial Virus (RSV) Infection in Canadian Infants: A Primer for Nurses.

Respiratory syncytial virus (RSV) is a leading cause of morbidity and hospitalization in young children, and prevention is the primary management strategy. At present, palivizumab, a monoclonal antibody providing immediate passive immunity, rather than a vaccine that induces active immunity, is the only preventive intervention used in routine practice internationally. In Canada, access varies across the country. Prophylaxis policies are mainly driven by cost-effectiveness analyses, and it is crucial that the full costs and benefits of any intervention are captured. Positive results from a new Canadian cost-effectiveness analysis of palivizumab will help address the current inequality in use while providing a framework for future models of RSV preventives. Nurses are the principal educators for parents about the risks of childhood RSV and optimal prevention via basic hygiene, behavioral and environmental measures, and seasonal prophylaxis. Nurses should be provided not only with regular, up-to-date, and accurate information on RSV and the clinical aspects of emerging interventions but be informed on the decision-making governing the use of preventive strategies.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Improved Genomic Prediction of Staphylococcus epidermidis Isolation Sources with a Novel Polygenic Score.

Staphylococcus epidermidis infections can be challenging to diagnose due to the species frequent contamination of clinical specimens and indolent course of infection. Nevertheless, S. epidermidis is the major cause of late-onset sepsis among premature infants and of intravascular infection in all age groups. Prior work has shown that bacterial virulence factors, antimicrobial resistances, and strains have up to 80% in-sample accuracy to distinguish hospital from community sources, but are unable to distinguish true bacteremia from blood culture contamination. Here, a phylogeny-informed genome-wide association study of 88 isolates was used to estimate effect sizes of particular genomic variants for isolation sources. A "polygenic score" was calculated for each isolate as the summed effect sizes of its repertoire of genomic variants. Predictive models of isolation sources based on polygenic scores were tested with in-samples and out-samples from prior studies of different patient populations. Polygenic scores from accessory genes (AGs) distinguished hospital from community sources with the highest accuracy to date, up to 98% for in-samples and 65% to 91% for various out-samples, whereas scores from single nucleotide polymorphisms (SNPs) had lower accuracy. Scores from AGs and SNPs achieved the highest in-sample accuracy to date, up to 76%, in distinguishing infection from contaminant sources within a hospital. Model training and testing data sets with more similar population structures resulted in more accurate predictions. This study reports the first use of a polygenic score for predicting a complex bacterial phenotype and shows the potential of this approach for enhancing S. epidermidis diagnosis.

Perspective: the potential of wastewater-based surveillance as an economically feasible game changer in reducing the global burden of pediatric respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading viral cause of childhood bronchiolitis and pneumonia causing over 3 million hospitalizations and 100,000 deaths in children under 5 years of age annually. Wastewater-based surveillance (WBS) has proven an effective early warning system for high-consequence pathogens, including SARS-CoV-2, polio, mpox, and influenza, but has yet to be fully leveraged for RSV surveillance. A model predicated on the Canadian province of Ontario demonstrates that implementation of a WBS system can potentially result in significant cost savings and clinical benefits when guiding an RSV preventive program with a long-acting monoclonal antibody. A network of integrated WBS initiatives offers the opportunity to help minimize the devastating global burden of RSV in children by optimizing the timing of preventive measures and we strongly advocate that its benefits continue to be explored.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Adoption in Canada of an international risk scoring tool to predict respiratory syncytial virus hospitalization in moderate-to-late preterm infants.

OBJECTIVE: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST. METHODS: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed. RESULTS: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores (p < .001) and risk categories (p < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%). CONCLUSIONS: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Introduction of biosimilar pegfilgrastim in France: Economic analysis of switching from originator.

OBJECTIVES: To assess the economic impact of introducing biosimilar pegfilgrastim compared to the current standard granulocyte colony-stimulating factor (G-CSF) practice in France. METHODS: A budget impact model was developed to investigate the impact of introducing pegfilgrastim biosimilar over 5 years. The model analysed drug acquisition costs, ambulatory costs, as well as costs associated with poor outcomes, and compared the current standard practice of long-acting and short-acting G-CSF to a revised practice including pegfilgrastim biosimilar in addition to standard practice treatments. The cost of switching to pegfilgrastim biosimilar, within a pharmacy setting, was analysed within the model using data from a survey of French pharmacists. RESULTS: The budget impact model calculated a cost saving of €51,007,531 over 5 years switching from the current standard practice to pegfilgrastim biosimilar. A sensitivity analysis accounting for variation in pegfilgrastim biosimilar uptake of 1) 15% in year 1 and 1% in years 2-5 and 2) 15% in years 1-5, estimated savings ranging between €29,377,784 and €79,847,194, respectively. A further analysis predicted cost savings of €287,344,835 over 5 years with the extension of pegfilgrastim biosimilar, at an uptake of 15% in year 1 and 7% in years 2-4, to both long-acting and short-acting G-CSF groups compared to unchanged current practice. CONCLUSIONS: The introduction of pegfilgrastim biosimilar will help to reduce cost and alleviate some of the financial pressure on the French healthcare system.

Challenges in the prevention or treatment of RSV with emerging new agents in children from low- and middle-income countries.

INTRODUCTION: Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs). AREAS COVERED: There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs. EXPERT OPINION: We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.

Association between respiratory syncytial virus hospitalization in infancy and childhood asthma.

INTRODUCTION: Respiratory syncytial virus infection in early childhood has been linked to longer-term respiratory morbidity; however, debate persists around its impact on asthma. The objective was to assess the association between respiratory syncytial virus hospitalization and childhood asthma. METHODS: Asthma hospital admissions and medication use through 18 years were compared in children with (cases) and without (controls) respiratory syncytial virus hospitalization in the first 2 years of life. All children born in National Health Service Scotland between 1996 and 2011 were included. RESULTS: Of 740 418 children (median follow-up: 10.6 years), 15 795 (2.1%) had a respiratory syncytial virus hospitalization at ≤2 years (median age: 143 days). Asthma hospitalizations were three-fold higher in cases than controls (8.4% vs 2.4%; relative risk: 3.3, 95% confidence interval [CI]: 3.1-3.5; P < .0001) and admission rates were four-fold higher (193.2 vs 46.0/1000). Cases had two-fold higher asthma medication usage (25.5% vs 14.7%; relative risk: 1.7, 95% CI: 1.7-1.8; P < .0001) and a three-fold higher rate of having both an asthma admission and medication (4.8% vs 1.5%; relative risk 3.1, 95% CI: 2.9-3.3; P < .0001). Admission rates and medication use remained significantly (P < .001) higher for cases than controls throughout childhood (admissions: ≥2-fold higher; medication: ≥1.5-fold higher). Respiratory syncytial virus hospitalization was the most significant risk factor for asthma hospitalizations±medication use (odds ratio: 1.9-2.8; P < .001). CONCLUSIONS: Respiratory syncytial virus hospitalization was associated with significantly increased rates and severity of asthma throughout childhood, which has important implications for preventive strategies.

Clinical burden of severe respiratory syncytial virus infection during the first 2 years of life in children born between 2000 and 2011 in Scotland.

National data from Scotland (all births from 2000 to 2011) were used to estimate the burden associated with respiratory syncytial virus hospitalisation (RSVH) during the first 2 years of life. RSVHs were identified using the International Classification of Diseases 10th Revision codes. Of 623,770 children, 13,362 (2.1%) had ≥ 1 RSVH by 2 years, with the overall rate being 27.2/1000 (16,946 total RSVHs). Median age at first RSVH was 137 days (interquartile range [IQR] 62-264), with 84.3% of admissions occurring by 1 year. Median length of stay was 2 (IQR 1-4) days and intensive care unit (ICU) admission was required by 4.3% (727) for a median 5 (IQR 2-8) days. RSVHs accounted for 6.9% (5089/73,525) of ICU bed days and 6.2% (64,395/1,033,121) of overall bed days (5370/year). RSVHs represented 8.5% (14,243/168,205) of all admissions between October and March and 14.2% (8470/59,535) between December and January. RSVH incidence ranged from 1.7 to 2.5%/year over the study period. Preterms (RSVH incidence 5.2%), and those with congenital heart disease (10.5%), congenital lung disease (11.2%), Down syndrome (14.8%), cerebral palsy (15.5%), cystic fibrosis (12.6%), and neuromuscular disorders (17.0%) were at increased risk of RSVH.Conclusions: RSV causes a substantial burden on Scottish paediatric services during the winter months.What is known:• Respiratory syncytial virus (RSV) is a leading cause of childhood hospitalisation.What is new:• This 12-year study is the first to estimate the burden of RSV hospitalisation (RSVH) in Scotland and included all live births from 2000 to 2011 and followed > 600,000 children until 2 years old.• The overall RSVH rate was 27.2/1000 children, with 2.1% being hospitalised ≥ 1 times.• RSVHs accounted for 6.2% of all inpatient bed days, which rose to 14.2% during the peak months of the RSV season (December-January), equating to over 1400 hospitalisations and nearly 5500 bed days each year.

IBD2020 global forum: results of an international patient survey on quality of care.

BACKGROUND/AIMS: IBD2020 is a global forum for standards of care in inflammatory bowel disease (IBD). The aim of the IBD2020 survey was to identify and describe variations in quality care of IBD. METHODS: Patients with IBD from Finland, Italy, France, Canada, Germany, UK, Spain and Sweden were surveyed during 2013 to 2014, covering: disease characteristics; impact on life and work; organization and perceived quality of care. RESULTS: Seven thousand five hundred and seven patients participated (median age, 39 years [range, 10-103 years]; 2,354 male [31.4%]), including 4,097 (54.6%) with Crohn's disease (CD) and 3,410 (45.4%) with ulcerative colitis (UC). Median time from symptom onset to diagnosis was 1 year for both CD (range, 0-47 years) and UC (range, 0-46 years), with no clear evidence of improvement in diagnostic delay over the preceding 24 years. Half of the patients (3,429; 50.0%) rated their care as "excellent" or "very good," with similar results for CD and UC across countries. Five factors were significantly (P<0.01) associated with perceived good quality of care: quality of specialist communication; review consultation being long enough; failure to share information; no access to a dietician; speed of advice. CONCLUSIONS: The IBD2020 survey has highlighted areas related to quality of care of IBD from the patients' perspective, with scope for improvement.

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants.

BACKGROUND: The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere. METHODS: Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated. RESULTS: The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3). CONCLUSIONS: This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).

AIM: We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This survey-based, observational study was conducted during 2014-2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important). RESULTS: The five most important factors for parents were: healthcare professionals' awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support. CONCLUSION: The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.

The influence of birth weight amongst 33-35 weeks gestational age (wGA) infants on the risk of respiratory syncytial virus (RSV) hospitalisation: a pooled analysis.

OBJECTIVE: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33°-356 weeks' gestational age (wGA) infants. STUDY DESIGN: Pooled analysis of data (n = 1218) from Spain, Germany, France and Italy. RESULT: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14 kg; p < 0.001) for both males (2.25 versus 2.18 kg; p = 0.049) and females (2.22 versus 2.11 kg, p = 0.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95 kg versus non-hospitalised 1.95 kg, p = 0.976; 34 wGA: 2.26 versus 2.14 kg, p = 0.007; 35 wGA: 2.37 versus 2.29 kg, p = 0.070), particularly female 34 wGA infants (female: 2.24 versus 2.08 kg, p = 0.019; male: 2.27 versus 2.20, p = 0.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation. CONCLUSIONS: In 33-35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation.

Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

BACKGROUND: Moderate-late preterm infants, 33-35 weeks' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants. METHODS: A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants' 33-35 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. RESULTS: The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. CONCLUSIONS: The burden of RSVH in moderate-late, 33-35 weeks' wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy.

Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?

Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital.