Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Evaluating the Impact of Statin Use on Influenza Vaccine Effectiveness and Influenza Infection in Older Adults.

BACKGROUND: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. METHODS: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. RESULTS: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for ß-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated ß-blocker users. CONCLUSIONS: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

Influenza Vaccine Effectiveness Against All-Cause Mortality Following Laboratory-Confirmed Influenza in Older Adults, 2010-2011 to 2015-2016 Seasons in Ontario, Canada.

BACKGROUND: Older adults are at increased risk of mortality from influenza infections. We estimated influenza vaccine effectiveness (VE) against mortality following laboratory-confirmed influenza. METHODS: Using a test-negative design study and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against all-cause mortality following laboratory-confirmed influenza for community-dwelling adults aged >65 years during the 2010-2011 to 2015-2016 influenza seasons. RESULTS: Among 54 116 older adults tested for influenza across the 6 seasons, 6837 died within 30 days of specimen collection. Thirteen percent (925 individuals) tested positive for influenza, and 50.6% were considered vaccinated for that season. Only 23.2% of influenza test-positive cases had influenza recorded as their underlying cause of death. Before and after multivariable adjustment, we estimated VE against all-cause mortality following laboratory-confirmed influenza to be 20% (95% confidence interval [CI], 8%-30%) and 20% (95% CI, 7%-30%), respectively. This estimate increased to 34% after correcting for influenza vaccination exposure misclassification. We observed significant VE against deaths following influenza confirmation during 2014-2015 (VE = 26% [95% CI, 5%-42%]). We also observed significant VE against deaths following confirmation of influenza A/H1N1 and A/H3N2, and against deaths with COPD as the underlying cause. CONCLUSIONS: These results support the importance of influenza vaccination in older adults, who account for most influenza-associated deaths annually.

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD. METHODS: We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010-11 to 2015-16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza. RESULTS: Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%-27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%-52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables. CONCLUSIONS: During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies.

The association between climate, geography and respiratory syncitial virus hospitalizations among children in Ontario, Canada: a population-based study.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization. METHODS: We conducted a population-based nested case-control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors. RESULTS: We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41). CONCLUSIONS: In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Creating enriched training sets of eligible studies for large systematic reviews: the utility of PubMed's Best Match algorithm.

INTRODUCTION: Solutions like crowd screening and machine learning can assist systematic reviewers with heavy screening burdens but require training sets containing a mix of eligible and ineligible studies. This study explores using PubMed's Best Match algorithm to create small training sets containing at least five relevant studies. METHODS: Six systematic reviews were examined retrospectively. MEDLINE searches were converted and run in PubMed. The ranking of included studies was studied under both Best Match and Most Recent sort conditions. RESULTS: Retrieval sizes for the systematic reviews ranged from 151 to 5,406 records and the numbers of relevant records ranged from 8 to 763. The median ranking of relevant records was higher in Best Match for all six reviews, when compared with Most Recent sort. Best Match placed a total of thirty relevant records in the first fifty, at least one for each systematic review. Most Recent sorting placed only ten relevant records in the first fifty. Best Match sorting outperformed Most Recent in all cases and placed five or more relevant records in the first fifty in three of six cases. DISCUSSION: Using a predetermined set size such as fifty may not provide enough true positives for an effective systematic review training set. However, screening PubMed records ranked by Best Match and continuing until the desired number of true positives are identified is efficient and effective. CONCLUSIONS: The Best Match sort in PubMed improves the ranking and increases the proportion of relevant records in the first fifty records relative to sorting by recency.

The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada.

IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

Calcitriol trend following pediatric cardiac surgery and association with clinical outcome.

BACKGROUND: Consistent with accepted practice in stable ambulatory populations, the majority of ICU research has evaluated vitamin D status using a single blood 25-hydroxyvitamin D (25(OH)D) level. Only a limited number of ICU studies have measured the active hormone, 1,25-dihydroxyvitamin D (calcitriol) and none have used change in calcitriol levels to evaluate axis functioning. The objective of this study was to describe the impact of Congenital Heart Disease (CHD) surgery on calcitriol levels and evaluate the relationship between change in postoperative levels and clinical course. METHODS: Secondary analysis of a prospective cohort study of 56 children undergoing surgery for CHD. RESULTS: Mean calcitriol levels dropped from 122.3 ± 69.1 pmol/L preoperatively to 65.3 ± 36.5 pmol/L (p < 0.0001) at PICU admission. The majority (61%, n = 34) were unable to increase calcitriol levels in the 48 h immediately following surgery. Post operative trend in calcitriol was inversely related to cardiovascular dysfunction, fluid requirements, ventilatory support and PICU length of stay (p < 0.01). CONCLUSION: CHD patients had significant dysfunction of the vitamin D axis immediately postoperatively, demonstrated by both a significant intraoperative decline in calcitriol and inability to increase levels. Interventional research will be required to determine whether the use of calcitriol, in addition to cholecalciferol, reduces postoperative illness severity.

Identifying significant and relevant events during pediatric transport: a modified Delphi study.

OBJECTIVES: Children must often be transported to dedicated pediatric centers to receive specialized medical and surgical care, which places them at risk for significant deterioration and life-threatening events. Studies designed to identify and mitigate these events have been limited by variability in the selection and definition of significant events. The objective of this study was to identify and evaluate indicators that represent significant events during the transport of pediatric patients and are relevant to future research initiatives in transport medicine. DESIGN: We conducted a modified Delphi study consisting of four iterations. SETTING: The expert panel included Canadian, interdisciplinary healthcare providers with transport experience. INTERVENTIONS: In the first Delphi iteration, experts suggested indicators for consideration and evaluated proposed indicators from the literature and introduced by the study steering committee. In subsequent iterations, respondents reevaluated all indicators that had not yet achieved a priori-defined consensus; group comments and aggregate scores for each indicator from previous iterations were provided. MEASUREMENTS AND MAIN RESULTS: The expert panel consisted of 16 physicians and 17 nonphysician healthcare providers from 10 Canadian institutions. In total, the panel evaluated 57 indicators, including 26 not previously presented in the literature. The expert panel determined 52 were significant and relevant to future studies in pediatric transport. The final indicator list includes trigger tools (interventions, physiological markers, and laboratory values) and team member safety and process issues. CONCLUSIONS: Using a systematic, modified Delphi approach, we developed an inclusive list of indicators for application to pediatric transport-related quality improvement and clinical research projects.

Impact of anesthesia and surgery for congenital heart disease on the vitamin d status of infants and children: a prospective longitudinal study.

BACKGROUND: Vitamin D is recognized as a pleiotropic hormone important for the functioning of organ systems, including those central to critical illness pathophysiology. Recent studies have reported associations between vitamin D status and outcome among critically ill adults and children. Preoperative vitamin D status, impact of operative techniques, and relationship between immediate postoperative vitamin D levels and clinical course have not been described in the pediatric congenital heart disease (CHD) population. The objective of this study was to describe the impact of CHD surgery on vitamin D status and relationship between postoperative levels and clinical course. METHODS: A prospective cohort study was conducted from 2009 to 2011 at a single tertiary care pediatric hospital. A total of 58 children with CHD were enrolled and blood collected preoperatively, intraoperatively, and postoperatively. Serum 25-hydroxyvitamin D (25OHD) was measured using liquid chromatography-mass spectrometry. RESULTS: The mean preoperative 25OHD was 58.0 nM (SD, 22.4), with 42% being deficient (<50 nM). Postoperatively, we identified a 40% decline in 25OHD to 34.2 nM (SD, 14.5) with 86% being deficient. Intraoperative measurements determined that initiation of cardiopulmonary bypass coincided with abrupt decline. CHD patients requiring catecholamines had lower postoperative 25OHD (38.2 vs. 26.5 nM, P=0.007), findings confirmed through multivariate logistic regression. Lower postoperative 25OHD was associated with increased fluid requirements and intubation duration. CONCLUSIONS: Most CHD patients are vitamin-D deficient postoperatively due to low preoperative levels and a significant intraoperative decline. Interventional studies will be required to determine whether prevention of postoperative vitamin D deficiency improves outcome.

[Vitamin D intake in young children with acute lower respiratory infection].

OBJECTIVE: To determine if vitamin D intake is associated with acute lower respiratory infections (ALRI) in children. METHODS: The vitamin D intakes of children younger than 5 years of age admitted to hospital with either bronchiolitis or pneumonia were compared to an unmatched control group of the same age without respiratory infection. Caregivers of 197 children completed a questionnaire collecting information on demographic variables, ALRI risk factors and diet. Associations of ALRI with vitamin D intake and other ALRI risk factors were determined. RESULTS: The mean vitamin D intake of children with ALRI was 48 IU/kg/d compared to 60 IU/kg/d in the control group. When controlling for age, ethnicity, socio-economic status, northern residence, breastfeeding, immunizations and smoking contact, children with a vitamin D intake of less than 80 IU/kg/d were greater than 4 times more likely to have ALRI compared to children with a vitamin D intake exceeding 80 IU/kg/d (OR=4.9; 95%CI: 1.5-16.4). CONCLUSIONS: A higher vitamin D intake than currently recommended might be needed to offer protection against diseases such as ALRI. Increased vitamin D supplementation could have important public health consequences, as bronchiolitis and pneumonia are the most common reasons for hospitalization in young children. (Full English version will be available online at www.amepc.org/tp.).

Health care costs of hospitalization of young children for respiratory syncytial virus infections: a population-based matched cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) infection poses a substantial clinical burden among infants and young children. We sought to determine the health care costs of hospitalizations attributable to RSV in Ontario, Canada, from the health care payer perspective. METHODS: For this population-based matched cohort study, we identified children younger than 24 months who were or were not hospitalized with RSV infections in 2006-2016. We performed a cost-of-illness analysis using linked administrative health data, with subjects stratified by gestational age and congenital heart disease, and propensity score-matched on established risk factors. The primary outcome was attributable health care costs per patient, reflecting the difference in direct medical costs between the groups, calculated to 12 months postdischarge in 2020 Canadian dollars. RESULTS: We identified 14 608 RSV-infected children, matched to 72 040 controls. The adjusted attributable cost of hospitalized RSV was $134 931 900 over 10 years, or $9240 per patient (95% confidence interval [CI] $8790-$9690). Health care costs escalated 3 days before hospitalization, and persisted up to 12 months after discharge. Increased costs were associated with major comorbidities, but not extreme premature birth. The highest mean attributable cost per patient was in the presence of hemodynamically significant heart disease ($60 110, 95% CI $26 700-$93 060). Infants born at 36-43 weeks' gestation constituted the greatest overall cost burden at $117 886 720. INTERPRETATION: Although the greatest direct medical costs per patient hospitalized with RSV infection are among children with cardiac disease, the greatest overall cost burden is from children born at or near term, who are not targeted by current prophylaxis strategies. The substantial attributable health care costs of RSV can inform cost-effectiveness analyses of novel RSV vaccines and prioritization of health care resources.

Family and Child Risk Factors for Early-Life RSV Illness.

BACKGROUND AND OBJECTIVES: Most infants hospitalized with respiratory syncytial virus (RSV) do not meet common "high-risk" criteria and are otherwise healthy. The objective of this study was to quantify the risks and relative importance of socioeconomic factors for severe, early-life RSV-related illness. We hypothesized several of these factors, particularly those indicating severe social vulnerability, would have statistically significant associations with increased RSV hospitalization rates and may offer impactful targets for population-based RSV prevention strategies, such as prophylaxis programs. METHODS: We used linked health, laboratory, and sociodemographic administrative data for all children born in Ontario (2012-2018) to identify all RSV-related hospitalizations occurring before the third birthday or end of follow-up (March 31, 2019). We estimated rate ratios and population attributable fractions using a fully adjusted model. RESULTS: A total of 11 782 RSV-related hospitalizations were identified among 789 484 children. Multiple socioeconomic factors were independently associated with increased RSV-related admissions, including young maternal age, maternal criminal involvement, and maternal history of serious mental health and/or addiction concerns. For example, an estimated 4.1% (95% confidence interval: 2.2 to 5.9) of RSV-related admissions could be prevented by eliminating the increased admissions risks among children whose mothers used welfare-based drug insurance. Notably, 41.6% (95% confidence interval: 39.6 to 43.5) of admissions may be prevented by targeting older siblings (eg, through vaccination). CONCLUSIONS: Many social factors were independently associated with early-life RSV-related hospitalization. Existing RSV prophylaxis and emerging vaccination programs should consider the importance of both clinical and social risk factors when determining eligibility and promoting compliance.

Characteristics and Outcomes of Young Children Hospitalized With Laboratory-confirmed Influenza or Respiratory Syncytial Virus in Ontario, Canada, 2009-2014.

BACKGROUND: Respiratory illnesses are a major contributor to pediatric hospitalizations, with influenza and respiratory syncytial virus (RSV) causing substantial morbidity and cost each season. We compared the characteristics and outcomes of children 0-59 months of age who were hospitalized with laboratory-confirmed influenza or RSV between 2009 and 2014 in Ontario, Canada. METHODS: We included hospitalized children who were tested for influenza A, influenza B and RSV and were positive for a single virus. We characterized individuals by their demographics and healthcare utilization patterns and compared their hospital outcomes, in-hospital cost and postdischarge healthcare use by virus type and by presence of underlying comorbidities. RESULTS: We identified and analyzed 7659 hospitalizations during which a specimen tested positive for influenza or RSV. Children with RSV were the youngest whereas children with influenza B were the oldest [median ages 6 months (interquartile range: 2-17 months) and 25 months (interquartile range: 10-45 months), respectively]. Complex chronic conditions were more prevalent among children with all influenza (sub)types than RSV (31%-34% versus 20%). In-hospital outcomes were similar by virus type, but in children with comorbidities, postdischarge outcomes varied. We observed no differences in in-hospital cost between viruses or by presence of comorbidities [overall median cost: $4150 Canadian dollars (interquartile range: $3710-$4948)]. CONCLUSIONS: Influenza and RSV account for large numbers of pediatric hospitalizations. RSV and influenza were similar in terms of severity and cost in hospitalized children. Influenza vaccination should be promoted in pregnant women and young children, and a vaccine against RSV would mitigate the high burden of RSV.

Can routinely collected laboratory and health administrative data be used to assess influenza vaccine effectiveness? Assessing the validity of the Flu and Other Respiratory Viruses Research (FOREVER) Cohort.

BACKGROUND: Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE. METHODS: We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies. RESULTS: We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010-11 to 2015-16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27-44%) in 2010-11 and 5% (95%CI, -2, 11%) in 2014-15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies. CONCLUSIONS: Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.

Vaccine effectiveness against laboratory-confirmed influenza hospitalizations among young children during the 2010-11 to 2013-14 influenza seasons in Ontario, Canada.

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6-59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010-11 to 2013-14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24-59 months, 48% (95%CI, 12%-69%) for children aged 6-23 months, 77% (95%CI, 47%-90%) for 2010-11, 59% (95%CI, 13%-81%) for 2011-12, 33% (95%CI, -18% to 62%) for 2012-13, and 72% (95%CI, 42%-86%) for 2013-14. VE in children aged 24-59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012-13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.

Vitamin D Deficiency in Pediatric Critical Care.

Vitamin D deficiency (VDD) is a well-established cause of pediatric bone and muscle disease. In addition, a role has been recognized for vitamin D in the health and stress response of other organs, including the cardiovascular, immune, and respiratory systems. As these organs are central to the development of and recovery from critical illness, VDD has been hypothesized to be a modifiable risk factor for ICU outcome. Over the past 5 years, a growing number of adult and pediatric critical care studies have investigated the prevalence of VDD and its association with illness severity and outcome. The adult studies have recently been synthesized in systematic reviews, with results that convincingly suggest the need for trials to determine whether optimization of vitamin D status improves outcome. In contrast, the pediatric ICU and related literature has not been similarly synthesized. The goal of this review is to describe vitamin D metabolism, known biological mechanisms, potential role in pathophysiology, and summarize the available pediatric intensive care unit (PICU) studies reporting on prevalence of VDD deficiency and its association with outcome. The problems with currently approved supplementation approaches and alternative strategies are discussed, including evidence from available RCTs in adult ICU. Altogether the results suggest that critically ill children are at risk for VDD, and that VDD appears to be associated with a worse clinical course. Clinical trials evaluating novel approaches to testing for and supplementing vitamin D require exploration.

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.

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 than control values after 24 h; immunoblotting showed a parallel 2.4-fold rise in Li16 protein. Regulatory influences on gene expression were assessed. Nuclear runoff assays confirmed that freezing initiated an increase in the rate of li16 transcription, and analysis of signal transduction pathways via in vitro incubation of liver slices implicated a cGMP-mediated pathway in li16 expression. Gene and protein expression in liver was also strongly stimulated by anoxia exposure, whereas the gene was less responsive to dehydration stress. The strong response of li16 to both freezing and anoxia, and the rapid down-regulation of the gene when oxygen was reintroduced, suggest that the Li16 protein may play a role in ischemia resistance during freezing.