Xenomake: a pipeline for processing and sorting xenograft reads from spatial transcriptomic experiments.

Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provide a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, quantification, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism specific reads, reduce sparsity of data by increasing gene counts, while maintaining biological relevance for studies.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay.

OBJECTIVE(S): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. METHODS: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. RESULTS: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. CONCLUSION(S): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Persistent Functional Decline Following Hospitalization with Influenza or Acute Respiratory Illness.

BACKGROUND/OBJECTIVES: Influenza is associated with significant morbidity and mortality, particularly for older adults. Persistent functional decline following hospitalization has important impacts on older adults' wellbeing and independence, but has been under-studied in relation to influenza. We aimed to investigate persistent functional change in older adults admitted to hospital with influenza and other acute respiratory illness (ARI). DESIGN: Protective observational cohort study. SETTING: Canadian Immunization Research Network Serious Outcomes Surveillance Network 2011 to 2012 influenza season. PARTICIPANTS: A total of 925 patients aged 65 and older admitted to hospital with influenza and other ARI. MEASUREMENTS: Influenza was laboratory-confirmed. Frailty was measured using a Frailty index (FI). Functional status was measured using the Barthel index (BI); moderate persistent functional decline was defined as a clinically meaningful loss of ≥10 to <20 points on the 100-point BI. Catastrophic disability (CD) was defined as a loss of ≥20 points, equivalent to full loss of independence in two basic activities of daily living. RESULTS: Five hundred and nineteen (56.1%) were women; mean age was 79.4 (standard deviation=8.4) years. Three hundred and forty-six (37.4%) had laboratory-confirmed influenza. Influenza cases had lower baseline function (BI = 77.0 vs 86.9, P < .001) and higher frailty (FI = 0.23 vs 0.20, P < .001) than those with other ARI. A total of 8.4% died, 8.2% experienced persistent moderate functional decline, and 9.9% experienced CD. Higher baseline frailty was associated with increased odds of experiencing functional decline, CD, and death. The experience of functional decline and CD, and its association with frailty, was the same for influenza and other ARI. CONCLUSION: Functional loss in hospital is common among older adults; for some this functional loss is persistent and catastrophic. This highlights the importance of prevention and optimal management of acute declines in health, including influenza, to avoid hospitalization. In the case of influenza, for which vaccines exist, this raises the potential of vaccine preventable disability.

Committee Opinion No. 399: Management of Tick Bites and Lyme Disease During Pregnancy.

OBJECTIVE: Lyme disease is an emerging infection in Canada caused by the bacterium belonging to the Borrelia burgdorferi sensu lato species complex, which is transmitted via the bite of an infected blacklegged tick. Populations of blacklegged ticks continue to expand and are now established in different regions in Canada. It usually takes more than 24 hours of tick attachment to transfer B. burgdorferi to a human. The diagnosis of early localized Lyme disease is made by clinical assessment, as laboratory tests are not reliable at this stage. Most patients with early localized Lyme disease will present with a skin lesion (i.e., erythema migrans) expanding from the tick bite site and/or non-specific "influenza-like" symptoms (e.g., arthralgia, myalgia, and fever). Signs and symptoms may occur from between 3 and 30 days following the tick bite. The care of pregnant patients with a tick bite or suspected Lyme disease should be managed similarly to non-pregnant adults, including the consideration of antibiotics for prophylaxis and treatment. The primary objective of this committee opinion is to inform practitioners about Lyme disease and provide an approach to managing the care of pregnant women who may have been infected via a blacklegged tick bite. INTENDED USERS: Health care providers who care for pregnant women or women of reproductive age. TARGET POPULATION: Women of reproductive age. EVIDENCE: In November 2018, Medline, EMBASE, PubMed, and CENTRAL databases were searched for 2 main categories: (1) Lyme disease and (2) other tick-borne diseases. Because the main focus was Lyme disease, and considering the limited number of the articles, no further filters were applied for publication time or type of study. For other tick-borne diseases, the results were restricted to a publication date within the last 10 years (2008-2018). The search terms were developed using MeSH terms and keywords including Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, and Southern Tick-Associated Rash Illness. All articles on Lyme disease and other tick-borne diseases with a target population of pregnant women were included; other groups and populations were excluded. VALIDATION METHODS: The content and recommendations of this committee opinion were drafted and agreed upon by the authors. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication.

Opinion du comité No 399 : Prise en charge des morsures de tiques et de la maladie de Lyme pendant la grossesse.

Objectif: La maladie de Lyme est une infection émergente au Canada. Causée par une bactérie appartenant au complexe d'espèces Borrelia burgdorferi sensu lato, elle est transmise par la morsure d'une tique à pattes noires infectée. Les populations de tiques à pattes noires continuent de se propager et sont maintenant établies dans différentes régions du Canada. Il faut habituellement plus de 24 heures de temps d'attachement de la tique pour que la B. burgdorferi soit transmise à l'humain. Le diagnostic de la maladie de Lyme au stade localisé précoce est posé au moyen d'une évaluation clinique, puisque les analyses de laboratoire ne sont pas fiables à ce stade. La plupart des patients atteints de la maladie de Lyme au stade localisé précoce manifestent une lésion cutanée (c.-à-d. érythème migrant) qui s'étend à partir du site de la morsure et/ou des symptômes non spécifiques qui rappellent l'influenza (p. ex. arthralgie, myalgie et fièvre). Les signes et symptômes peuvent se manifester de 3 à 30 jours après la morsure de tique. Il y a lieu de prendre en charge les patientes enceintes qui présentent une morsure de tique ou une maladie de Lyme soupçonnée en leur prodiguant des soins semblables à ceux de la population adulte non enceinte, ce qui implique d'envisager le recours aux antibiotiques pour la prophylaxie et le traitement. L'objectif principal de la présente opinion du comité est de renseigner les praticiens sur la maladie de Lyme et de fournir une façon d'aborder la prise en charge des soins prodigués aux femmes enceintes qui pourraient avoir été infectées par une morsure de tique à pattes noires. Utilisateurs concernés: Les fournisseurs de soins de santé qui prodiguent des soins aux patientes enceintes ou aux femmes en âge de procréer. Population cible: Les femmes en âge de procréer. Données probantes: En novembre 2018, des recherches ont été effectuées dans les bases de données Medline, EMBASE, PubMed et CENTRAL relativement à deux catégories principales : (1) maladie de Lyme, (2) autres maladies transmises par les tiques. Puisque la recherche était principalement axée sur la maladie de Lyme et compte tenu du nombre limité d'articles à ce sujet, aucun filtre supplémentaire n'a été appliqué pour la date de publication ou le type d'étude. Pour ce qui est des autres maladies transmises par les tiques, les résultats ont été restreints à une date de publication qui s'inscrit dans les 10 dernières années (2008­2018). Les termes de recherche ont été déterminés au moyen des termes de recherche MeSH et de mots clés : Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, et Southern Tick-Associated Rash Illness. Tous les articles portant sur la maladie de Lyme et autres maladies transmises par les tiques comprenant une population cible de femmes enceintes ont été inclus; les autres groupes et populations ont été exclus. Méthodes de validation: Le contenu et les recommandations de la présente opinion du comité ont été rédigés et acceptés par les auteurs. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication.

Frailty Hinders Recovery From Influenza and Acute Respiratory Illness in Older Adults.

BACKGROUND: We examined frailty as a predictor of recovery in older adults hospitalized with influenza and acute respiratory illness. METHODS: A total of 5011 patients aged ≥65 years were admitted to Canadian Serious Outcomes Surveillance Network hospitals during the 2011/2012, 2012/2013, and 2013/2014 influenza seasons. Frailty was measured using a previously validated frailty index (FI). Poor recovery was defined as death by 30 days postdischarge or an increase of more than 0.06 (≥2 persistent new health deficits) on the FI. Multivariable logistic regression controlled for age, sex, season, influenza diagnosis, and influenza vaccination status. RESULTS: Mean age was 79.4 (standard deviation = 8.4) years; 53.1% were women. At baseline, 15.0% (n = 750) were nonfrail, 39.3% (n = 1971) were prefrail, 39.8% (n = 1995) were frail, and 5.9% (n = 295) were most frail. Poor recovery was experienced by 21.4%, 52.0% of whom had died. Frailty was associated with lower odds of recovery in all 3 seasons: 2011/2012 (odds ratio [OR] = 0.70; 95% confidence interval [CI], 0.59-0.84), 2012/2013 (OR = 0.72; 95% CI, 0.66-0.79), and 2013/2014 (OR = 0.75; 95% CI, 0.69-0.82); results varied by season, influenza status, vaccination status, and age. CONCLUSIONS: Increasing frailty is associated with lower odds of recovery, and persistent worsening frailty is an important adverse outcome of acute illness.

Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015.

BACKGROUND: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age. METHODS: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years). RESULTS: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Influenza surveillance case definitions miss a substantial proportion of older adults hospitalized with laboratory-confirmed influenza: A report from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network.

OBJECTIVE: Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults. DESIGN: Prospective cohort study. SETTING: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults. METHODS: Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index. RESULTS: Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58-82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6-52.6) for younger adults versus 44.6% (95% CI, 43.6-45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7-65.6) of younger adults versus 57.1% (95% CI, 55.9-58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions. CONCLUSIONS: A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.

Streptococcus pneumoniae serotype 3 is masking PCV13-mediated herd immunity in Canadian adults hospitalized with community acquired pneumonia: A study from the Serious Outcomes Surveillance (SOS) Network of the Canadian immunization research Network (CIRN).

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. METHODS: Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. RESULTS: Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. CONCLUSION: Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD.

BACKGROUND: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal. METHODS: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations. RESULTS: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]). CONCLUSIONS: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population. TRIAL REGISTRY: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network).

BACKGROUND: Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons. METHODS: The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death. RESULTS: Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%). CONCLUSIONS: While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191.

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network.

BACKGROUND: Consideration of cost determinants is crucial to inform delivery of public vaccination programs. OBJECTIVES: To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. METHODS: Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. RESULTS: Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. CONCLUSION: The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context.

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

BACKGROUND: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. METHODS: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. RESULTS: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). CONCLUSIONS: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.