Should individuals use influenza vaccine effectiveness studies to inform their decision to get vaccinated?

Studies on the effectiveness of seasonal influenza vaccine can affect an individual's perception of the ability of this vaccine to protect against influenza. However, vaccine effectiveness studies are designed to inform public health decisions rather than for individual decision-making. This overview explains what vaccine effectiveness means and why vaccine effectiveness estimates can vary. Individual variation in the response to seasonal influenza vaccine is based upon risk factors such as age, underlying health conditions, immune status and risk of infection and complications. Therefore, an individual's decision to get vaccinated should be primarily informed by their risk of influenza illness and their risk of transmitting influenza to vulnerable people.

Effectiveness of hand hygiene practices in preventing influenza virus infection in the community setting: A systematic review.

BACKGROUND: Hand hygiene is known to be an effective infection prevention and control measure in health care settings. However, the effectiveness of hand hygiene practices in preventing influenza infection and transmission in the community setting is not clear. OBJECTIVE: To identify, review and synthesize available evidence on the effectiveness of hand hygiene in preventing laboratory-confirmed or possible influenza infection and transmission in the community setting. METHODS: A systematic review protocol was established prior to conducting the review. Three electronic databases (MEDLINE, Embase and the Cochrane Library) were searched to identify relevant studies. Two reviewers independently screened the titles, abstracts and full-texts of studies retrieved from the database searches for potential eligibility. Data extraction and quality assessment of included studies were performed by a single reviewer and validated by a second reviewer. Included studies were synthesized and analyzed narratively. RESULTS: A total of 16 studies were included for review. Studies were of low methodological quality and there was high variability in study design, setting, context and outcome measures. Nine studies evaluated the effectiveness of hand hygiene interventions or practices in preventing laboratory-confirmed or possible influenza infection in the community setting; six studies showed a significant difference, three studies did not. Seven studies assessed the effectiveness of hand hygiene practices in preventing laboratory-confirmed or possible influenza transmission in the community setting; two studies found a significant difference and five studies did not. CONCLUSION: The effectiveness of hand hygiene against influenza virus infection and transmission in the community setting is difficult to determine based on the available evidence. In light of its proven effectiveness in other settings, there is no compelling evidence to stop using good hand hygiene practice to reduce the risk of influenza infection and transmission in the community setting.

Summary of the NACI Seasonal Influenza Vaccine Statement for 2018-2019.

BACKGROUND: There are many different influenza vaccines authorized for use in Canada and new evidence on influenza and vaccines is emerging all the time. The National Advisory Committee on Immunization (NACI) provides recommendations annually regarding seasonal influenza vaccines to the Public Health Agency of Canada (PHAC). OBJECTIVE: To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2018-2019 influenza season in light of two NACI reviews conducted on 1) the risk of serious influenza-related complications in children and adults with neurologic and neurodevelopment conditions and 2) the efficacy/effectiveness of high-dose and adjuvanted inactivated influenza vaccines in persons 65 years of age and older. METHODS: For both topics, NACI's Influenza Working Group developed a predefined search strategy to identify all eligible studies, assessed their quality, summarized and analyzed the findings, proposed recommendations and identified the Grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. RESULTS: NACI concludes there is fair evidence to recommend that children and adults with neurologic and neurodevelopment conditions are groups for whom influenza immunization is particularly recommended (Evidence Grade B recommendation). On choosing influenza vaccines for persons 65 years of age and older, at a programmatic level, NACI recommends that any of the four influenza vaccines available for use should be used. There is insufficient evidence to make a comparative recommendation on the use of these vaccines at a programmatic level (Grade I). At an individual level, NACI recommends that high-dose trivalent inactivated influenza vaccine (TIV) should be offered over standard-dose TIV to persons 65 years of age and older (Grade A). There is insufficient evidence to make comparative recommendations on the use of MF59-adjuvanted TIV and quadrivalent inactivated influenza vaccine over standard-dose TIV (Grade I). CONCLUSION: NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, people who provide essential community services and people in direct contact during culling operations with poultry infected with avian influenza.

Summary of the NACI Statement on Seasonal Influenza Vaccine for 2017-2018.

BACKGROUND: Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC). OBJECTIVE: To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2017-2018 influenza season. METHODS: Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations. The recommendations include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). RESULTS: The annual statement has been updated for the 2017-2018 influenza season to incorporate recommendations for the use of live attenuated influenza vaccine (LAIV) that were contained in two addenda published after the 2016-2017 statement. These recommendations were 1) that egg-allergic individuals may be vaccinated against influenza using the low ovalbumin-containing LAIV licensed for use in Canada and 2) to continue to recommend the use of LAIV in children and adolescents 2-17 years of age, but to remove the preferential recommendation for its use. CONCLUSION: NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, and others as indicated.

Immunization guidance products: Different levels of detail for different uses.

The National Advisory Committee on Immunization (NACI) provides expert and evidence-based advice to the Public Health Agency of Canada (PHAC) on the use of human vaccines in Canada. This advice is presented in a variety of publications for different uses. A recent survey identified some confusion regarding the various NACI publication products. The objective of this article is to identify the level of detail and appropriate uses of the different NACI products. NACI statements provide a synthesis of current evidence and expert opinion on new vaccines or new indications for vaccines to inform immunization practices, policies and programs. NACI literature reviews inform new NACI statements and are published after the statement to inform readers about current literature on a specific immunization topic. The Canadian Immunization Guide (CIG) is a practice-oriented guide that synthesizes all the NACI statements and is updated regularly. NACI statement summaries are published in the Canada Communicable Disease Report (CCDR) and provide a high level overview of these statements shortly after they are published. These products provide a variety of options for users to choose how in-depth they wish to explore the evidence base and process for producing recommendations for immunization in Canada.

Evolving practice: X-linked agammaglobulinemia and lung transplantation.

X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency syndrome characterized by agammaglobulinemia, recurrent infections and bronchiectasis. Despite the association with end-stage bronchiectasis, the literature on XLA and lung transplantation is extremely limited. We report a series of 6 XLA patients with bronchiectasis who underwent lung transplantation. Short-term outcomes were excellent however long-term outcomes were disappointing with a high incidence of pulmonary sepsis and chronic lung allograft dysfunction (CLAD).

Minimal important difference in field walking tests in non-cystic fibrosis bronchiectasis following exercise training.

BACKGROUND: The 6-min walk distance (6MWD) and incremental shuttle walk distance (ISWD) are clinically meaningful measures of exercise capacity in people with non-cystic fibrosis (CF) bronchiectasis, but the change in walking distance which constitutes clinical benefit is undefined. This study aimed to determine the minimal important difference for the 6MWD and ISWD in non-CF bronchiectasis. METHODS: Thirty-seven participants with mean FEV1 70% predicted completed both field walking tests before and after an 8-week exercise program. The minimal important difference was calculated using a distribution-based and anchor-based method, with the global rating of change scale used. RESULTS: The mean change in 6MWD in participants who reported themselves to be unchanged was 10 m, compared to 36 m (small change) and 45 m (substantial change) (p = 0.01). For the ISWD, the mean change in participants who reported themselves to be unchanged was 33 m, compared to 54 m (small change) and 73 m (substantial change) (p = 0.04). The anchor-based method defined the minimal important difference for 6MWD as 24.5 m (AUC 0.76, 95% CI 0.61-0.91) and for ISWD as 35 m (AUC 0.88, 95% CI 0.73-0.99), based on participant's global rating of change. The distribution-based method indicated a value of 22.3 m for the 6MWD and 37 m for the ISWD. There was excellent agreement between the two methods for the 6MWD (kappa = 0.91) and the ISWD (kappa = 0.92). CONCLUSIONS: Small changes in 6MWD and ISWD may represent clinically important benefits in people with non-CF bronchiectasis. These data are likely to assist in the interpretation of change in exercise capacity following intervention.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies.

BACKGROUND AND AIMS: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. METHODS: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. RESULTS: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. CONCLUSION: Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Campylobacteriosis outbreak associated with ingestion of mud during a mountain bike race.

One of the largest reported campylobacteriosis outbreaks in Canada occurred in June 2007 in British Columbia, associated with a mountain bike race that took place in muddy conditions. A retrospective cohort study was conducted and environmental samples were collected and tested. There were 537 racers included in the study and 225 racers (42%) reported diarrhoeal illness after the race. C. jejuni clinical isolates (n=14) were found to be identical by multi-locus sequence typing. Although univariate analysis suggested water consumption and mud exposure as significant risk factors, multivariate analysis revealed that on direct ingestion mud was significantly associated with illness (OR 4·08, 95% CI 2·03-8·21). Contaminated mud was thus the most likely source of Campylobacter infection. We identified other unpublished reports of outbreaks associated with bike races in rainy or muddy conditions; these underscore the importance of educating racers and raising public awareness of the risks of mud ingestion.

Clinical lesson: eosinophilic oesophagitis, a new diagnosis to swallow.

Eosinophilic oesophagitis (EoE) is a recently described condition that has gained increasing recognition over the past 5 years. Despite this, many clinicians remain unaware of EoE, often leading to diagnostic delay and therefore significant morbidity. The diagnosis of EoE should be considered in any patient with a history of intermittent or continuous dysphagia, or oesophageal food impaction. It should be strongly suspected in young patients, particularly men, presenting with dysphagia and a history of atopy. Here, three patients are presented that highlight common features of EoE. In addition, a clinical review of the worldwide literature is provided to heighten physician awareness and understanding of the condition.

Clinical determinants of the 6-Minute Walk Test in bronchiectasis.

BACKGROUND: The 6-Minute Walk Test (6MWT) is a widely used measurement of functional exercise capacity in chronic lung disease. While exercise intolerance has been identified in patients with bronchiectasis, the clinical determinants of the 6MWT in this population have not been examined. The aim of this study was to 1) establish the relationship between the 6-Minute Walk Distance (6MWD), disease severity and Health-Related Quality of Life (HRQOL) and 2) identify predictors of exercise tolerance in adults with bronchiectasis. METHODS: The 6MWT was performed in 27 patients with bronchiectasis (mean [SD] FEV(1) 73.9% predicted [23.4]). Disease severity was assessed using spirometry and HRCT scoring while HRQOL was evaluated using the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36). The relationships were evaluated using correlation and multiple regression. RESULTS: The 6MWD correlated positively with FVC (r=0.52, p<0.01), generations of bronchopulmonary divisions (r(s)=0.38, p<0.05) and SF-36 physical summary (r=0.71, p<0.001) while a negative correlation was observed between all domains of the SGRQ (all correlations r>0.5, p<0.001). Multiple regression analysis indicated that the SGRQ activity, symptom scores and generations of bronchial divisions involved were identified as independent predictors of the 6MWD, explaining 76% of the variance. CONCLUSIONS: Measures of HRQOL demonstrated a stronger association with the 6MWD compared to physiological measures of disease severity in patients with predominantly mild to moderate bronchiectasis.

Regenerating optic axons restore topography after incomplete optic nerve injury.

Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons intact, restores normal topography. Strict RGC axon topography allowed us to preserve RGC axons on one side of the nerve (projecting to medial tectum) while lesioning those on the other side (projecting to lateral tectum). Topography and response properties for both RGC axon populations were assessed electrophysiologically. The majority of intact RGC axons retained appropriate topography in medial tectum and had normal, consistently brisk, reliable responses. Regenerate RGC axons fell into two classes: those that projected topographically to lateral tectum with responses that tended to habituate and those that lacked topography, responded weakly, and habituated rapidly. Axon tracing by localized retinal application of carbocyanine dyes supported the electrophysiological data. RGC soma counts were normal in both intact and axotomized RGC populations, contrasting with the 30% RGC loss after complete injury. Unlike incomplete optic nerve injury in mammals, where RGC axon regeneration fails and secondary cell death removes many intact RGC somata, lizards experience a "win-win" situation: intact RGC axons favorably influence the functional outcome for regenerating ones and RGCs do not succumb to either primary or secondary cell death.

The balance of NMDA- and AMPA/kainate receptor-mediated activity in normal adult goldfish and during optic nerve regeneration.

Retinotectal topography is established during development and relies on the sequential recruitment of glutamate receptors within postsynaptic tectal cells. NMDA receptors underpin plastic changes at early stages when retinal ganglion cell (RGC) terminal arbors are widespread and topography is coarse; AMPA/kainate receptors mediate fast secure neurotransmission characteristic of mature circuits once topography is refined. Here, we have examined the relative contributions of these receptors to visually evoked activity in normal adult goldfish, in which retinotectal topography is constantly adjusted to compensate for the continual neurogenesis and the addition of new RGC arbors. Furthermore, we examined animals at two stages of optic nerve regeneration. In the first, RGC arbors are widespread and receptive fields large resulting in coarse topography; in the second, RGC arbors are pruned to reduce receptive fields leading to refined topography. Antagonists were applied to the tectum during multiunit recording of postsynaptic responses. Normal goldfish have low levels of NMDA receptor-mediated activity and high levels of AMPA/kainate. When coarse topography has been restored, NMDA receptor-mediated activity is increased and that of AMPA/kainate decreased. Once topography has been refined, the balance of NMDA and AMPA/kainate receptor-mediated activity returns to normal. The data suggest that glutamatergic neurotransmission in normal adult goldfish is dual with NMDA receptors fine-tuning topography and AMPA receptors allowing stable synaptic function. Furthermore, the normal operation of both receptors allows a response to injury in which the balance can be transiently reversed to restore topography and vision.

Failure to restore vision after optic nerve regeneration in reptiles: interspecies variation in response to axotomy.

Optic nerve regeneration within the reptiles is variable. In a snake, Viper aspis, and the lizard Gallotia galloti, regeneration is slow, although some retinal ganglion cell (RGC) axons eventually reach the visual centers (Rio et al. [1989] Brain Res 479:151-156; Lang et al. [1998] Glia 23:61-74). By contrast, in a lizard, Ctenophorus ornatus, numerous RGC axons regenerate rapidly to the visual centers, but unless animals are stimulated visually, the regenerated projection lacks topography and animals remain blind via the experimental eye (Beazley et al. [2003] J. Neurotrauma 20:1263-1269). V. aspis, G. galloti, and C. ornatus belong respectively to the Serpentes, Lacertidae, and Agamidae within the Eureptilia, the major modern group of living reptiles comprising the Squamata (snakes, lizards, and geckos) and the Crocodyllia. Here we have extended the findings on Eureptilia to include two geckos (Gekkonidae), Cehyra variegata and Nephrurus stellatus. We also examined a turtle, Chelodina oblonga, the Testudines being the sole surviving representatives of the Parareptilia, the more ancient reptilian group. In all three species, visually elicited behavioral responses were absent throughout regeneration, a result supported electrophysiologically; axonal tracing revealed that only a small proportion of RGC axons crossed the lesion and none entered the contralateral optic tract. RGC axons failed to reach the chiasm in C. oblonga, and in G. variegata, and N. stellatus RGC axons entered the opposite optic nerve; a limited ipsilateral projection was seen in G. variegata. Our results support a heterogeneous response to axotomy within the reptiles, each of which is nevertheless dysfunctional.

Effect of smoking on MAP kinase-induced modulation of IL-8 in human alveolar macrophages.

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking. The smoking-induced regulation of interleukin (IL)-8 by extracellular signal-regulated kinase (ERK)-1 and -2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers. IL-8 production was dependent on phosphorylation of ERK-1 and -2 and p38 MAPK, as examined by PD 098059 (10 microM), an inhibitor of the upstream activator of MAPK kinase (MKK)-1, and SB 203580 (10 microM), an inhibitor of p38 MAPK. IL-8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK-2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK-2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK-1 and -2. Lipopolysaccharide-induced IL-8 production was dependent on activation of NF-kappaB, as examined by SN 50 (100 microM), an inhibitor of NF-kappaB translocation, and the specific NF-kappaB inhibitor kinase-2 inhibitor, AS 602868 (10 microM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF-kappaB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay. It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor-kappaB activation to increase lipopolysaccharide-induced interleukin-8 production in alveolar macrophages.