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.

Respiratory Syncytial Virus Immunoprophylaxis with Palivizumab: 12-Year Observational Study of Usage and Outcomes in Canada.

OBJECTIVE: This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH). STUDY DESIGN: It involves a large, Canadian prospective (2005-2017) observational multicenter study of children at high risk for RSV infection. RESULTS: A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); "miscellaneous" (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The "miscellaneous" group increased over time (4.4% in 2005-2006 to 22.5% in 2016-2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual "unclassified" group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4-18.2; p < 0.0005) more likely to have RSVH than infants without risk factors. Three adverse events occurred; none were fatal. CONCLUSION: Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required. KEY POINTS: · Main indications were prematurity (63.3%); "miscellaneous" (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%).. · The proportion of children in the "miscellaneous" group, comprised of those with trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual "unclassified" group, increased over time (4.4% in 2005-2006 to 22.5% in 2016-2017).. · Respiratory illness-related hospitalization occurred in 2,054 children (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH: 1.6%)..

Hospitalization for Respiratory Syncytial Virus in Children with Down Syndrome Less than 2 Years of Age: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare the respiratory syncytial virus (RSV)-related hospitalization rate, hospital length of stay (LOS), and need for assisted ventilation in children aged <2 years with Down syndrome and those without Down syndrome. STUDY DESIGN: MEDLINE, Embase, and CINAHL databases were searched from inception up to December 2017. Studies that provided data on RSV-related hospitalization in children aged <2 years with Down syndrome and those without Down syndrome were included. Data were independently extracted in pairs by 2 reviewers and synthesized with random-effects meta-analysis. RESULTS: In 10 studies including a total of 1 748 209 children, 12.6% of the children with Down syndrome (491 of 3882) were hospitalized with RSV infection. The presence of Down syndrome was associated with a significantly higher risk of RSV-related hospitalization (relative risk [RR], 6.06; 95% CI, 4.93-7.45; I2 = 65%; Grading of Recommendations, Assessment, Development and Evaluation [GRADE], moderate). RSV-related LOS (mean difference, 2.11 days; 95% CI, 1.47-2.75 days; I2 = 0%; GRADE, low), and the need for assisted ventilation (RR, 5.82; 95% CI, 1.81-18.69; I2 = 84%; GRADE, low). Children with Down syndrome without congenital heart disease (RR, 6.31; 95% CI, 4.83-8.23; GRADE, moderate) also had a significantly higher risk of RSV-related hospitalization. The risk of RSV-related hospitalization remained significant in the subgroup of children aged <1 year (RR, 6.25; 95% CI, 4.71-8.28; GRADE, high). CONCLUSION: RSV-related hospitalization, hospital LOS, and the need for assisted ventilation are significantly higher in children with Down syndrome aged <2 years compared with those without Down syndrome. The results should prompt reconsideration of the need for routine RSV prophylaxis in children with Down syndrome up to 2 years of age.

Respiratory syncytial virus hospitalization and incurred morbidities the season after prophylaxis.

OBJECTIVES: The primary objective of this study was to determine the incidence and incurred morbidities of Respiratory syncytial virus (RSV)-related hospitalization (RSVH), the season following completion of prophylaxis. METHODS: A retrospective study was conducted of all infants enrolled in a prophylaxis clinic in one institution during the 2009 to 2014 RSV seasons. RSV infection was identified by Diseases codes and confirmed by RSV-positivity. Data were classified into five groups based on indications for prophylaxis. The incidence of RSVH was calculated. For each subgroup, differences in characteristics between children with and without RSVH were analyzed by independent t test or chi-square test. RESULTS: During five RSV seasons, 827 infants were enrolled. RSVH incidence the season following prophylaxis was 2.1% (n=17/827). Children with chronic lung disease (CLD) had the highest RSVH incidence (7.7%; n=4/52) followed by preterms 33 to 35 weeks gestation (2.5%; n=4/162), those with complex medical disorders (2.2%; n=3/135), those with congenital heart disease (1.5%; n=1/66) and preterms less than or equal to 32 weeks gestation (1.2%; n=5/412). There was no statistically significant association between indications for prophylaxis and RSVH (Fisher exact test, P=0.060). The odds of RSVH were 4.9 times greater (odds ratio [OR]=4.9; 95% CI: 1.53, 15.55; P=0.007) in CLD compared to those without CLD. The median length of RSVH stay was 4 days; 58.8% (n=10/17) required oxygen (median 1 day); 29.4% (n=5/17) required intensive care. CONCLUSIONS: Infants with CLD are at highest risk for RSVH in the season postprophylaxis and may merit palivizumab for more than two seasons dependent on disease severity. However, larger prospective studies are necessary to confirm the findings before embarking on a strategy of providing prophylaxis for a third RSV season.

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.

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.

Molecular evolution of respiratory syncytial virus fusion gene, Canada, 2006-2010.

To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSV-positive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006-2010. Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.

Use of thrombolytic agents to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis. Thrombolytic agents are used for the management of life and/or organ-threatening thrombosis. Literature on the efficacy and safety of thrombolytic agents in neonates is limited. We reviewed the evidence on dosing, administration, monitoring and treatment duration of tissue plasminogen activator (tPA), streptokinase and urokinase (URK) in neonates (≤ 28days). A systematic literature search was conducted of current databases from inception until 31 March 2021. The initial search yielded 6881 articles and 18 were retained for review. tPA, streptokinase and URK was utilized in 12, seven and four studies on 115, 51 and 16 patients, respectively. The dose range for tPA, streptokinase and URK was 0.01 -0.6 mg/kg/h, 50-2000 and 1000-0 000 units/kg/h, respectively, and treatment duration ranged from 30 min to 30 days. This is the first study to objectively summarize the efficacy and safety of thrombolytic agents in neonates. Overall, thrombolysis was associated with 87.9% complete or partial thrombus resolution and 7.4% recurrence risk. The bleeding risk associated with thrombolytic agents was 23.1% on pooled analysis, which is higher than other anticoagulants. Larger prospective studies are required to determine effective dosing regimens of these therapeutic drugs and further clarify their efficacy and safety. Blood Coagul Fibrinolysis 33:000-000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

The impact of prophylaxis on paediatric intensive care unit admissions for RSV infection: a retrospective, single-centre study.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections and hospitalizations in children aged < 2 years. The aim of this retrospective, single-centre study was to examine the characteristics of patients admitted to a paediatric intensive care unit (PICU) with RSV infection following the implementation of a RSV prophylaxis programme. Electronic hospital medical records of all PICU admissions for RSV infection were searched from 2003 to 2009. Data on baseline demographics, underlying disease, criteria for hospitalization, respiratory diagnosis and management, complications and palivizumab prophylaxis were collected. A total of 181 patients were admitted with RSV infection, accounting for 5.7% of all admissions. Eighty-four percent were ≤ 2 years of age. Majority (70.2%) had no underlying medical illness, and 79.6% received antibiotics as part of their medical treatment. Comparison of children aged ≤ 2 years and those >2 years revealed that fewer of the younger cohort (20.4% versus 79.3%; p < 0.001) had an underlying medical condition. RSV infection occurred in 3.3% (n = 6) children who had received palivizumab prophylaxis, and there were two deaths. The results indicate that > 88% of all PICU admissions would not qualify for RSV prophylaxis under our established guidelines and 66% of the children aged ≤ 2 years were > 36 weeks gestation and are not currently targeted for prophylaxis. The number of high-risk infants admitted to PICU with RSV infection has likely plateaued, and further reductions in admission rates may only be realised with the use of universal, vaccine immunization programmes.

Respiratory Syncytial Virus Prophylaxis in Immunocompromised Children: Outcomes From the Canadian RSV Evaluation Study of Palivizumab Registry Over Twelve Seasons (2005-2017).

BACKGROUND: Immunocompromised children are at increased risk for respiratory syncytial virus (RSV) infection with associated morbidity and mortality. Prophylaxis is usually provided to these children on a case-by-case basis. METHODS: Immunocompromised children who received ≥1 injection of palivizumab were prospectively enrolled across 32 Canadian sites, between 2005 and 2017, during the RSV season. We assessed respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios (HRs) in immunocompromised children versus infants' prophylaxed for standard indications (SI: prematurity ≤35 weeks' gestation, bronchopulmonary dysplasia, and congenital heart disease) and complex medical disorders (CMD). Data were analyzed using t-tests, χ and Cox proportional hazards adjusted for confounders. RESULTS: A total of 25,003 infants were recruited; 214 immunocompromised, 4283 CMD, 20,506 SI. On average, children received 4.4 ± 1.3 injections. A total of 16,231 children were perfectly adherent (58.4% immunodeficiency, 68.9% CMD, 64.2% SI; P < 0.0005). A higher proportion of immunocompromised children were aboriginal and exposed to smoking compared with CMD and SI. Immunocompromised children also had a higher median; gestational and enrollment age and birth weight compared with CMD and SI. Immunodeficient children had a higher RIH risk compared with SI (HR = 2.4, 95% confidence interval, 1.3-4.7, P = 0.009) but were similar to CMD (HR = 1.7, 95% confidence interval, 0.9-3.4, P = 0.118). RSVH in prophylaxed, immunocompromised children was similar to CMD (HR < 0.005, P = 0.955) and SI (HR < 0.005, P = 0.953). CONCLUSIONS: Immunocompromised children who received palivizumab had an increased RIH hazard compared with the SI group. Similar RSVH hazard between the 3 groups suggests that immunocompromised children may benefit from palivizumab during the RSV season.

Comparison of the cost of hospitalization for respiratory syncytial virus disease versus palivizumab prophylaxis in Canadian Inuit infants.

BACKGROUND: The objectives were to compare actual respiratory syncytial virus (RSV) hospitalization rates and costs in a cohort of Inuit infants to hypothetical palivizumab prophylaxis strategies for infants of all gestational ages in the Eastern Canadian Arctic. METHODS: Incidence and costs of RSV hospitalization were collected for infants admitted to the Baffin Regional Hospital in 2002, before the initiation of palivizumab. There was a comparison of the actual costs to the costs associated with 8 palivizumab strategies stratified by age (<6 months, <1 year) and location (overall, town [Iqaluit], rural communities). It was assumed that each category would receive universal palivizumab prophylaxis resulting in a 78% decrease in RSV admissions. The net costs incurred, number needed to treat (NNT), and incremental costs per hospitalization avoided were calculated for each comparison. RESULTS: There was a great variation in the rates and costs associated with RSV admissions between Iqaluit and the communities. For infants <1 year of age residing in Iqaluit, the mean admission cost was $3915, and palivizumab prophylaxis had an NNT of 20.4 and cost of $162,551 per admission avoided. For rural infants <6 months, the mean cost of admission was $23,030, and palivizumab prophylaxis resulted in an NNT of 3.9 to 2.5 and cost savings of up to $8118 per admission avoided. CONCLUSIONS: Due to the high rates and costs associated with RSV admissions, administration of palivizumab in rural communities in the Canadian Arctic to infants less than 6 months of age could result in net cost savings.

Respiratory Syncytial Virus Prophylaxis in Neurologic and Muscular Disorders in the Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab.

BACKGROUND: This study aimed to examine the risk of respiratory-related hospitalization in children with neurologic and muscular disorders (NMDs) who received respiratory syncytial virus (RSV) prophylaxis in the Canadian RSV Evaluation Study of Palivizumab. METHODS: Canadian RSV Evaluation Study of Palivizumab is a prospective registry of children who received ≥1 palivizumab injection among 32 Canadian sites. Demographic data were collected at enrollment, and respiratory events were documented monthly. Cox proportional hazard analyses were conducted to compare respiratory illness-related hospitalization (RIH) and RSV-related hospitalization (RSVH) among children with NMD and those prophylaxed for standard indications (SI) and complex medical disorders. RESULTS: Group differences were found in enrollment age and weight, birth weight, household crowding, neonatal stay and supplemental oxygen requirement (all P < 0.05). RIH and RSVH incidences were 19.2%, 3.3% (NMD, n = 605); 6.0%, 1.5% (SI, n = 20,335), 9.4%, 1.6% (complex medical disorders, n = 4063), respectively. Children with NMD had a higher risk of RIH (hazard ratio [HR]: 1.90; 95% confidence interval (CI): 1.41-2.56; P < 0.0005) than those with SI. RSVH risk was greater in children with NMD compared with both the SI (HR: 2.26; 95% CI: 1.38-3.72; P = 0.001) and complex medical disorders groups (HR: 2.74; 95% CI: 1.55-4.84; P = 0.001). Children with more severe infantile onset NMD had a higher risk of RIH than those with general hypotonic disorders (HR: 1.69; 95% CI: 1.06-2.68; P = 0.027) but not RSVH. CONCLUSIONS: Children with NMD who received palivizumab had a higher risk of both RIH and RSVH. Our results imply that all children with NMD, regardless of disease severity, are at risk for respiratory-related illness and RSV infection.

The association of platelets with failed patent ductus arteriosus closure after a primary course of indomethacin or ibuprofen: a systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the association of platelet counts and pharmacotherapeutic failure in preterms with a patent ductus arteriosus (PDA). METHODS: MEDLINE, Embase, Science Citation Index, abstracts and conference proceedings were searched, and principal authors contacted. Included studies reported indomethacin or ibuprofen use for PDA closure, compared a group which failed treatment versus a group which did not and reported the association between platelet counts and indomethacin or ibuprofen failure. Two reviewers independently screened results and assessed methodological quality using the Newcastle-Ottawa Scale. Results are expressed as mean difference in platelet counts and summary odds ratios (OR) using a random effects model. RESULTS: 1105 relevant studies were identified; eight involving 1087 preterms were included. Platelet counts were significantly lower in infants who failed pharmacotherapy (Meandifference:-30.88 × 109/L; 95% CI:-45.69 × 109,-16.07 × 109/L; I2 = 24%; pheterogeneity = 0.24). Similar results were obtained based on either pharmacotherapeutic agent. Treatment failure was also significantly associated with pre-treatment thrombocytopenia (summary OR:1.75; 95% CI:1.23-2.49, I2 = 36%, pheterogeneity = 0.20). CONCLUSIONS: Platelet counts are significantly lower in preterms who fail primary treatment for PDA. Pre-treatment thrombocytopenia is associated with higher odds of failure. Further cohort studies reporting platelet counts in prostaglandin inhibitor failure are needed for meta-analyses to firmly establish or refute a stronger association.

Comparing First- and Second-year Palivizumab Prophylaxis in Patients With Hemodynamically Significant Congenital Heart Disease in the CARESS Database (2005-2015).

BACKGROUND: Respiratory syncytial virus hospitalization (RSVH) rates in children <2 years of age with hemodynamically significant congenital heart disease (HSCHD) are 2- to 4-fold higher compared with healthy term infants. Pediatric recommendations differ as to whether palivizumab is beneficial beyond 1 year of age. The objective of this study was to determine whether differences exist in respiratory-related illness hospitalization (RIH) and RSVH in HSCHD infants receiving palivizumab during the first year versus second year of life in the Canadian Registry of Palivizumab. METHODS: The Canadian Registry of Palivizumab is a prospective database of infants who received ≥1 dose of palivizumab in 32 hospitals from 2005 to 2015. Demographic data were collected at enrollment and RIH events recorded monthly. Infants <24 months of age with HSCHD were recruited. RESULTS: Of 1909 HSCHD infants, 1380 (72.3%) in the first year (mean age, 4.2 months) and 529 (27.7%) in the second year of life (mean age, 17.8 months) received prophylaxis. Baseline demographics for day-care attendance, multiple births, enrollment age and weight differed between the groups (all P < 0.05). Additionally, second year infants had a more complicated neonatal course, with significantly longer length of stay (51.2 vs. 24.9 days) compared with those in the first year. The RIH and RSVH rates in the first year were 11.2% and 2.3% and in the second year were 10.6% and 1.7%. Cox regression analysis showed similar hazard for RIH [hazard ratio, 1.9; 95% confidence interval: 0.7-4.6; P = 0.18] and RSVH [hazard ratio, 2.0; 95% confidence interval: 0.2-16.5; P = 0.52]. CONCLUSIONS: Infants in the first and second year of life had a similar RSVH hazard. These findings suggest that infants in the second year with HSCHD, who remain unstable, are equally at risk for RSVH and merit prophylaxis.

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. METHODS: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. FINDINGS: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries. INTERPRETATION: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

How to use unfractionated heparin to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis due to risk factors such as catheter instrumentation, an evolving coagulation system and congenital heart disease. Unfractionated heparin (UFH) is one of the most commonly used anticoagulants in neonates. Published guidelines delineate dosing and monitoring protocols for UFH therapy in newborns. However, challenging clinical situations frequently present that warrants healthcare providers to think critically beyond the range of guidelines, and judiciously resolve specific problems. This review focuses briefly on the epidemiology of neonatal thrombosis and the use of UFH in this population. It is followed by a discussion on dosing of UFH in neonates, limited evidence that forms the basis of published guidelines with justification for a treatment regimen that precludes the use of a heparin loading dose in newborns and monitoring of UFH therapy with currently available tests such as antifactor Xa (anti-Xa) level and activated partial thromboplastin time (APTT). Multiple studies have demonstrated a lack of correlation between anti-Xa levels and APTT as well as between different anti-Xa assays. Many centers world-wide rely only on APTT for monitoring purposes and do not have access to anti-Xa assays. To address these difficulties, we propose two practical algorithms, with and without the use of anti-Xa levels that clinicians can follow when monitoring UFH therapy in neonates. The article concludes with an overview of the side-effects of UFH.

Patent foramen ovale and stroke in childhood: A systematic review of the literature.

BACKGROUND: Stroke in association with a patent foramen ovale (PFO) may be due to paradoxical embolization via a right to left intracardiac shunt but the exact contribution of PFO to stroke or stroke recurrence in childhood remains unclear. METHODS: To review the relationship of a PFO with stroke, and evaluate associated co-morbidities. An electronic database literature search of Pubmed, Cochrane and EMBASE was performed from January 2000-December 2014. RESULTS: 149 articles were retrieved, with overlap for diagnosis, management, treatment and outcome. 65 reports were utilized for the comprehensive review. Majority of childhood arterial ischemic stroke and transient ischemic attacks are associated with prothrombotic disorders or arteriopathy. Transthoracic echocardiography with a Valsalva maneuver is highly sensitive as a screening tool but may be falsely positive. Transthoracic echocardiography with color Doppler and a concurrent bubble contrast study are excellent for visualizing the atrial septum and PFO and identifying a right to left shunt. Current literature does not support PFO closure for cryptogenic stroke in young adults without an associated risk of thromboembolism. CONCLUSIONS: High quality research in the pediatric population is lacking and most of the data is extrapolated from adults. Paradoxical embolism from a PFO as a cause of transient ischemic attack or stroke is a diagnosis of exclusion. PFO closure should be individualized based on significant shunting and risk factors such that maximum benefit is derived from the procedure. A young person with a PFO and stroke should be thoroughly investigated to rule out other etiologies.

Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization and outcomes.

OBJECTIVE: To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus (RSV) infection. DESIGN: Observational, prospective, longitudinal, multicenter study. SETTING: Eighteen hospitals and pediatric clinics located in six provinces across Canada. PATIENTS: Infants enrolled in the palivizumab Special Access Programme of Canada's Therapeutic Products Programme throughout the 1999 to 2000 RSV season. Most were premature infants born at < or = 32 weeks of gestation and/or had bronchopulmonary dysplasia. METHODS AND MAIN OUTCOME MEASURES: Neonatal and demographic data were recorded for each subject. The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections. RESULTS: There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000. Most subjects received 5 injections with high compliance. Prophylaxis was discontinued in 2% of children. There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children. Eighty-six of these were managed in an outpatient setting, and 30 required hospitalization. The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was 2.4%. Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%). CONCLUSIONS: This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings confirm the results of the major randomized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis.