Using routinely collected laboratory and health administrative data to assess influenza vaccine effectiveness: introducing the Flu and Other Respiratory Viruses Research (FOREVER) Cohort

Introduction Annual evaluation of influenza vaccine effectiveness (VE) is required because of frequent changes to circulating and vaccine strains. Traditionally, VE studies enroll patients who fulfill case definitions for respiratory infections and are tested for influenza. VE estimates generated from convenience samples of routinely collected specimens might be biased. Objectives and Approach We assessed the validity of using data from respiratory specimens collected during clinical encounters to estimate VE. We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking respiratory virus laboratory test results from 2009-2014 from 11 public health and 8 hospital laboratories across Ontario to health administrative databases, including databases with billing claims for physician- and pharmacist-administered influenza vaccines. We evaluated the presence of information and selection biases when using these data and estimated VE in community-dwelling older adults (>65) using the test-negative design under conditions that emulated the inclusion criteria in traditional VE studies. Results The FOREVER Cohort included test results from 283,711 respiratory specimens obtained from 216,730 individuals. The overall linkage proportion to health administrative databases using deterministic and probabilistic linkage methods was 97.5%. Influenza positivity for older adults with unknown lag between illness onset and specimen collection was similar to those for whom illness onset date was documented to be ≤7 days before specimen collection, suggesting minimal outcome misclassification associated with information bias. The likelihood of influenza testing was similar between vaccinated and unvaccinated individuals, suggesting an absence of selection bias that could arise when a case definition for influenza testing is not employed. Lastly, VE estimates were similar under various conditions, demonstrating the robustness of using these data, and were comparable to published estimates. Conclusion/Implications The FOREVER Cohort can be used to estimate VE with negligible bias. Compared to traditional VE studies that are limited to recruited patients, routinely collected specimens create a larger, more generalizable sample. Linkage to health administrative databases can identify those with comorbidities and permit evaluation of VE in high-risk groups

Freeze-induced expression of a novel gene, fr47, in the liver of the freeze-tolerant wood frog, Rana sylvatica

The ability to endure the freezing of body fluids is well developed as an adaptation for winter survival in several species of woodland frogs. Recently, the mechanisms supporting natural freeze tolerance have been shown to include the expression of novel genes. One such novel gene, fr47, codes for a 390-amino acid protein present in the livers of freeze-tolerant anurans (Rana sylvatica, Pseudacris crucifer, Hyla versicolor) but not in freeze-intolerant species (Rana pipiens, Scaphiopus couchii). Regulatory influences on gene and protein expression were investigated using R. sylvatica. Northern blot analysis showed that transcript levels were increased following 24 h of freezing (5.1-fold), 24 h of anoxia exposure (6.4-fold), or the loss of 20% of total body water (2.7-fold). Immunoblotting with anti-FR47 antibody indicated that protein levels increased during freezing and thawing, but decreased somewhat during anoxia or dehydration exposure, although rebounding during recovery. These results suggest that (i) FR47 function is important for freeze survival, and (ii) that control at the protein level may be exerted posttranscriptionally. Finally, assessment of putative signal transduction pathways regulating fr47 gene expression, via in vitro incubations of liver slices, indicated the involvement of a protein kinase C-mediated pathway

High Rate of Medical Emergency Team Activation in Children with Tracheostomy.

Pediatric in-patients with tracheostomy (PIT) are at high risk for clinical deterioration. Medical emergency teams (MET) have been developed to identify high-risk patients. This study compared MET activation rates between PITs and the general ward population. This was a retrospective cohort study conducted at a tertiary pediatric hospital. The primary outcome (MET activation) was obtained from a database. Between 2008 and 2014, the MET activation rate was significantly higher in the PIT group than the general ward population (14 vs. 2.9 per 100 admissions

Pediatric Chronic Critical Illness: Protocol for a Scoping Review

BackgroundImprovements in the delivery of intensive care have increased survival among even the most critically ill children, thereby leading to a growing number of children with chronic complex medical conditions in the pediatric intensive care unit (PICU). Some of these children are at a significant risk of recurrent and prolonged critical illness, with higher morbidity and mortality, making them a unique population described as having chronic critical illness (CCI). To date, pediatric CCI has been understudied and lacks an accepted consensus case definition. ObjectiveThis study aims to describe the protocol and methodology used to perform a scoping review that will describe how pediatric CCI has been defined in the literature, including the concept of prolonged PICU admission and the methodologies used to develop any existing definitions. It also aims to describe patient characteristics and outcomes evaluated in the included studies. MethodsWe will search four electronic databases for studies that evaluated children admitted to any PICU identified with CCI. We will also search for studies describing prolonged PICU admission, as this concept is related to pediatric CCI. Furthermore, we will develop a hybrid crowdsourcing and machine learning (ML) methodology to complete citation screening. Screening and data abstraction will be performed by 2 reviewers independently and in duplicate. Data abstraction will include the details of population definitions, demographic and clinical characteristics of children with CCI, and evaluated outcomes. ResultsThe database search, crowd reviewer recruitment, and ML algorithm development began in March 2021. Citation screening and data abstraction were completed in April 2021. Final data verification is ongoing, with analysis and results anticipated to be completed by fall 2021. ConclusionsThis scoping review will describe the existing or suggested definitions of pediatric CCI and important demographic and clinical characteristics of patients to whom these definitions have been applied. This review’s results will help inform the development of a consensus case definition for pediatric CCI and set a priority agenda for future research. We will use and demonstrate the validity of crowdsourcing and ML methodologies for improving the efficiency of large scoping reviews. International Registered Report Identifier (IRRID)DERR1-10.2196/3058

Identification and characterization of a novel freezing inducible gene, li16, in the wood frog Rana sylvatica.

The wood frog Rana sylvatica survives for weeks during winter hibernation with up to 65% body water frozen as ice. Natural freeze tolerance includes both seasonal and freeze-induced molecular adaptations that control ice formation, deal with long-term ischemia, regulate cell volume changes, and protect macromolecules. This report identifies and characterizes a novel freeze-inducible gene, li16, that codes for a protein of 115 amino acids. Northern blot analysis showed that li16 transcript levels rose quickly during freezing to reach levels 3.7-fold higher