Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations.

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Resolution-increased fiber-optic strain sensor with a large dynamic range driven by white light.

The white light interferometer is advantageous for wavelength division multiplexing (WDM), but the excessive noise floor limits its application in practicality. In this Letter, we propose a fiber-optic sensor driven by a broadband light source, which uses a fiber-optic Fabry-Perot cavity and a reference interferometer to enhance strain resolution. In the experiment, the strain resolution of a 5.86 m resonant sensor is 18.5 fɛ/H z at 1.5 kHz, while the maximum detectable signal is over 230 rad at 1 kHz. With low cost, this method provides a new, to the best of our knowledge, solution for WDM sensing arrays with a large dynamic range.

An enveloped virus-like particle alum-adjuvanted cytomegalovirus vaccine is safe and immunogenic: A first-in-humans Canadian Immunization Research Network (CIRN) study.

INTRODUCTION: Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). METHODS: Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. RESULTS: Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. CONCLUSIONS: An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.

Synergistic modulation of electrical and thermal transport toward promising n-type MgOCuSbSe2 thermoelectric performance by MO-intercalated CuSbSe2.

The layered ternary CuSbSe2 semiconductor with ultralow thermal conductivity is particularly suitable for thermoelectric applications. Nevertheless, its poor electrical conductivity greatly lowers the dimensionless figure of merit ZT and accordingly limits its thermoelectric applications. Here, we use first-principles calculations combined with semi-classical Boltzmann transport theory to evaluate the thermoelectric properties of MO-intercalated (M = Mg, Ca, Sr, and Ba) CuSbSe2. Compared with CuSbSe2, MO-intercalated CuSbSe2 semiconductors, as a new class of semiconductors, host distorted lattices with low symmetry monoclinic structures. Such a structure feature provides desired channels for electron transport between adjacent layers and accordingly enhances electrical transport properties. Meanwhile, the MO intercalation effectively softens phonons and gives rise to an ultralow lattice thermal conductivity in MOCuSbSe2. These synergistically yield a high figure of merit ZT of ∼4.17 for MgO-intercalated CuSbSe2 at 200 K with electron doping being n = 1018 cm-3. Our study provides an effective route to improve the thermoelectric performance of layered CuSbSe2 by designing new multicomponent thermoelectric compounds with alternatively stacked [CuSbSe2] (electronic conduction units) and [MO] (electronic insulation units) layers. The approach can be extended to similar chalcostibite compounds for screening and designing thermoelectric materials.

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.

Fabrication of poly (styrene-acrylate)/silver nanoparticle-graphene oxide composite antibacterial by in situ Pickering emulsion polymerization.

Graphene oxide (GO) nanosheets decorated with silver nanoparticles (AgNPs) were easily synthesized by chemical reduction, and the prepared nanocomposite was then used as a stabilizer in the Pickering emulsion polymerization of poly (styrene-acrylate) to prepare PSA/AgNPs-GO composites. The AgNPs-GO nanocomposites were fully characterized by TEM, FTIR, Raman, SEM and XPS, which demonstrated that about 5-30 nm AgNPs with spherical, octahedral and cubic structures were decorated on the surface of wrinkled GO nanosheets. TEM photos and EDS spectrum of composites showed that the transparent GO nanosheets decorated with AgNPs were covered on the surface of PSA latexes and the AgNPs were uniformly dispersed on the surface of the PSA latexes without aggregation. The average diameter of composite latexes was obviously bigger than that of PSA latexes. However, the role of surfactant and the properties of hydrophilicity decreased the average diameter and WCA of composites while increasing the additions of AgNPs-GO nanocomposites. AFM images disclosed that wrinkled GO nanosheets decorated with AgNPs dispersed on the surface of composite films. XPS data proved clearly that silver was present only in metallic form and migration occurred during film-formation. TGA curves confirmed the composite film displayed better thermal stability than that of PSA. The results of antibacterial activity revealed that composite films had exhibited antibacterial properties against both E. coli and S. aureus, and the latter showed better antibacterial efficacy than the former. The nano-silver polyacrylate coatings with antibacterial activity explored in current work have wide application in the fields of wood coatings, leather finishing, and so on.

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.

Fibronectin promotes tumor angiogenesis and progression of non-small-cell lung cancer by elevating WISP3 expression via FAK/MAPK/ HIF-1α axis and activating wnt signaling pathway.

BACKGROUND: Fibronectin, an extracellular matrix protein, has been reported to be associated with heterogeneous cancer stemness, angiogenesis and progression in multiple cancer types. However, the roles and the underlying mechanism of fibronectin on the progression NSCLC need to be further elucidated. METHODS: Public dataset such as Kaplan-Meier Plotter was used to determine the prognostic significance of genes. The correlation of different protein expression in clinical and xenograft tissues was tested by immunohistochemistry experiment. Both in vitro and in vivo experiments were performed to determine the role of fibronectin on the tumor growth, metastasis, and angiogenesis in NSCLC. The activation of key signaling pathway under fibronectin was examined by WB assay. RNA-seq was applicated to screening the target gene of fibronectin. Rescue experiment was performed to confirm the role of target gene in fibronectin-mediated function in NSCLC. Finally, luciferase and CHIP assays were used to elucidate the mechanism by which fibronectin regulated the target gene. RESULTS: Our results revealed that fibronectin was up-regulated in cancer tissues compared with the normal ones in NSCLC patients. Dish- coated fibronectin enhanced the tumor growth, metastasis, and angiogenesis of NSCLC in vitro and in vivo by promoting EMT and maintaining stemness of NSCLC cells. As expected, fibronectin activated FAK and its downstream MAPK/ERK signaling pathway. WISP3 was screened as a potential target gene of fibronectin. Interestingly, WISP3 effectively activated Wnt signaling pathway, and knockdown of WISP3 effectively blocked the influence of fibronectin on the migration, invasion and vascular structure formation potential of NSCLC cells. Our data also manifested that fibronectin elevated the transcription of WISP3 gene by promoting the binding of HIF-1α to the promoter region of WISP3 in NSCLC cells. CONCLUSIONS: Our findings sketched the outline of the route for fibronectin exert its role in NSCLC, in which fibronectin activated downstream FAK and MAPK/ERK signaling pathways, and mediated the accumulation of HIF-1α. Then, HIF-1α enabled the transcription of WISP3, and subsequently promoted the activation of Wnt signaling pathway, and finally enhanced the tumor growth, metastasis, and angiogenesis in NSCLC.

Preparation and characterization of silanized graphene oxide based polyacrylate composites in situ copolymerization.

In the present work, graphene oxide (GO) was initially prepared by the modified Hummers' method and then surface modification with 3-Methacryloxypropyltrimeth- oxysilane (MPS) was carried out. The silanized GO based polyacrylate (PA) composite emulsion was fabricated via in situ copolymerization. The covalent bonds formed between GO and PA matrix were proposed to improve the dispersion of MPS-GO in composites. FTIR spectra, Raman spectra, XPS and XRD data confirmed that oxidation and modification were occurred, and oxygen-containing functional groups and CC groups were introduced on the side of GO, respectively. Two kinds of structures were observed in composite latexes, and the average diameter of composite latexes (107 nm) was larger than that of PA latexes (87 nm). FTIR spectra also disclosed that reactive MPS-GO had already successfully copolymerized with the PA matrix. AFM images demonstrated that wrinkled GO nanosheets were homogeneously dispersed and incorporated into the PA matrix. The water contact angle (WCA) was found increasing as the addition of MPS-GO, although the composite films exhibited obvious hydrophilicity with increasing the content of MPS-GO.

Intensity Equalization of Bidirectional Fiber Laser Based on a Non-Reciprocal Optical Attenuator.

The application of a bidirectional laser requires the laser intensity in both directions to be balanced. However, the CW and CCW light intensities in current bidirectional erbium-doped fiber laser experiments differ due to the gain competition effect. There is no report on equalizing the intensity in the CW and CCW directions. This paper proposes a bidirectional non-reciprocal optical attenuator using the Faraday optical rotation effect. Continuous attenuation adjustment is realized by changing the angle between the polarizer's transmission axis and the linear polarized light. In this study, we analyzed the influence of different parameters on the device's performance, built a non-reciprocal attenuator, and tested the bidirectional attenuation curve, which was consistent with the simulation results. The device was integrated into a bidirectional fiber laser, and the light intensity in both directions was balanced through non-reciprocal adjustment. Combined with closed-loop control, the average intensity difference fluctuation between the two directions was controlled at 0.28% relative to the average power, realizing stable long-term bidirectional fiber laser intensity equalization.

Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.

BACKGROUND: Lung cancer is the most common cause of cancer-related death globally. There are several reasons for this high mortality rate, including metastasis to multiple organs, especially the brain. Exosomes play a pivotal role in tumor metastasis by remodeling the microenvironment of remote target organs and promoting the pre-metastatic niche's formation. Since astrocytes are indispensable for maintaining the homeostasis of brain microenvironment, it's of great interest to explore the influence of lung cancer cell-derived exosomes on astrocytes to further understand the mechanism of lung cancer brain metastasis. RESULTS: Twenty four h after co-culture of H1299 cell-derived exosomes and SVG P12 cells, the viability of astrocytes decreased and the apoptosis increased. The levels of cytokines in the supernatant including GROα/CXCL1, IFN-γ, IL-3, IL-5, IL-15, LIF, M-CSF, NGF, PDGF, and VEGF were significantly enhanced, while IL-7 secretion was significantly reduced. Meanwhile, apoptosis-related proteins MAP2K1, TUBA1C, RELA, and CASP6 were up-regulated. And the differentially expressed proteins were involved in regulating metabolic pathways. CONCLUSION: Exosomes of H1299 could induce apoptosis of astrocytes as well as promote their secretion of cytokines that were conducive to the formation of the inflammatory microenvironment and immunosuppressive microenvironment, and affect their metabolic pathways, thus facilitating the formation of pre-metastatic niche in lung cancer brain metastases.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring BRAF mutations.

Background: Despite immune checkpoint inhibitors (ICI) being widely used to treat patients with advanced non-small cell lung cancer (NSCLC), few studies examine the role of ICI in patients with proto-oncogene B-Raf, serine/threonine kinase (BRAF) mutations. Methods: A retrospective study was conducted for patients with BRAF-mutant NSCLC who received treatment at Shanghai Pulmonary Hospital between 2014 and 2022. Primary end point was progression-free survival (PFS). Secondary end point was best response (RECIST, version 1.1). Results: The study involved a total of 34 patients with 54 treatments recorded. The median PFS for the whole cohort was 5.8 months and the overall objective response rate (ORR) was 24%. Patients who were treated with ICI combined with chemotherapy reported a median PFS of 12.6 months and an ORR of 44%. Those who were treated with non-ICI therapy came with a median PFS of 5.3 months and an ORR of 14%. Specifically, patients had better clinical benefits with first-line ICI-combined therapy. The PFS was 18.5 months whereas that of non-ICI group was 4.1 months. The ORR was 56% in ICI-combined group and 10% in non-ICI cohort. Conclusions: The findings observed an evidential and significant susceptibility to ICIs combined therapy in patients with BRAF-mutant NSCLC, especially in first-line treatment.

Risk factors for mechanical complications of peripherally inserted central catheters in children.

OBJECTIVE: To determine risk factors for mechanical (noninfectious) complications in peripherally inserted central catheters (PICCs) in children. DESIGN: Retrospective cohort study. SETTING: Pediatric tertiary-care center in Nova Scotia, Canada. PATIENTS: Pediatric patients with a first PICC insertion. METHODS: All PICCs inserted between January 2001 until 2016 were included. Age-stratified (neonates vs non-neonates) Fine-Grey competing risk proportional hazard models were used to model the association between each putative risk factor and the time to mechanical complication or removal of the PICC for reasons not related to a mechanical complication. Models were adjusted for confounding variables identified through directed acyclic graphs. RESULTS: Of 3,205 patients with PICCs, 706 had mechanical complications (22% or 14 events/1000 device days). For both neonates and older children, disease group, lumen count, and prior leak were all associated with mechanical complications in the adjusted proportional hazards model. Access vein and prior infection were also associated with mechanical complications for neonates, and age group was associated with mechanical complications among non-neonates. CONCLUSIONS: We have identified several risk factors for mechanical complications in patients with PICCs that will help improve best practices for PICC insertion and care.

Healthcare provider awareness, attitudes, beliefs, and behaviors regarding the role of pharmacists as immunizers.

We explored perceptions of healthcare providers in Nova Scotia and New Brunswick about pharmacists as immunizers. Pharmacists' scopes of practice are increasingly broadening to include immunization, and providers and policymakers may find meaning in the lessons we learned. Invitations to participate in our online survey were circulated by professional associations, health authorities, and in social media posts. A total of 204 healthcare providers completed our survey, of whom 59.3% were pharmacists, 17.6% were nurses, and 23.0% were physicians. Nurses (30.6%) and physicians (34.0%) experienced fewer logistical barriers to immunizing compared to pharmacists, 71.1% of whom identified practice logistics as a determinant in offering vaccines to patients (p < .001). Pharmacists were most supportive of the expansion of their own scope of practice to include the provision of vaccines to adults (95.9%) and children as young as five years (92.6%) compared to nurses (72.2% and 69.4%) and physicians (61.7% and 40.4%) (p < .001). Diversity of opinion was evident even among pharmacists about whether they should be permitted to vaccinate children younger than five years. Nurse and physician respondents had lower odds of thinking pharmacists have enough training to vaccinate (p < .001), that vaccines should be given in a pharmacy (p < .001), and of supporting the expansion of pharmacists' scope of practice (p < .001) than pharmacists did in the multivariable analyses. Pharmacists are well-positioned and willing to vaccinate and generally have support from their nurse and physician peers, but logistical challenges and interprofessional complexities persist as barriers to optimizing immunization by pharmacists.

In most Canadian provinces and territories, pharmacists are trained and able to give vaccines alongside traditional immunizers like doctors and nurses. In this study, we surveyed the views of immunizing professionals (pharmacists, doctors, and nurses) in Nova Scotia and New Brunswick about pharmacists giving vaccines. Healthcare providers were invited to do our online survey by their professional associations, provincial health authorities, and through posts on social media. Healthcare providers generally supported pharmacists giving vaccines, but not without some conditions from nurses, doctors, and some pharmacists themselves. We found all three professions to be very vaccine positive but learned that pharmacists experience barriers to giving vaccines that their nurse and doctor colleagues do not such as working by themselves, volume of work, time, compensation, and record-keeping. We highlight the importance of collaboration between immunizing professionals, acknowledgment of pharmacists' training as immunizers, a uniform funding model for all immunization providers, and a central and accessible vaccine registry. We also suggest that until power dynamics and complexities between professions are addressed in meaningful and structural ways, we might not enjoy the full benefits of pharmacists as immunizers. We hope these findings are useful in places where pharmacists cannot yet vaccinate and where pharmacists' scopes of practice are in the process of widening to include immunization.

Frequency-Modulated Signal Measurement Using Closed-Loop Methodology.

Frequency-modulated (FM) signals are widely used in sensing, measurement, and signal detection due to their strong anti-interference and easy transmission characteristics. Although the high-precision measurement methods for static signals are quite complete, the high-precision measurement methods for dynamic FM signals still need to be studied, and the measurement accuracy in the high-sampling system still has room for improvement. Traditionally, the equal-precision measurement method is widely applied in most scenarios. However, its accuracy is limited by the quantization error of ±1 word and the sampling gate time, making it difficult to improve the frequency measurement accuracy while ensuring a high sampling rate at the same time. In this paper, a high-precision feedback frequency measurement system with the capability to eliminate the quantization error of ±1 word is proposed. The proposed system consists of two stages, the rough measurement stage based on the equal-precision measurement method and the precise measurement stage based on the negative feedback tracking architecture using the phase-frequency detector (PFD) and direct digital synthesizer (DDS). The effectiveness and feasibility of the system are verified by both simulation and experiment. At the sampling rate of 2 kHz, the frequency measurement accuracy is improved by more than 30 dB.

Deblurring of Sound Source Orientation Recognition Based on Deep Neural Network.

Underwater target detection and identification technology are currently two of the most important research directions in the information disciplines. Traditionally, underwater target detection technology has struggled to meet the needs of current engineering. However, due to the large manifold error of the underwater sonar array and the complexity of ensuring long-term signal stability, traditional high-resolution array signal processing methods are not ideal for practical underwater applications. In conventional beamforming methods, when the signal-to-noise ratio is lower than -43.05 dB, the general direction can only be vaguely identified in the general direction. To address the above challenges, this paper proposes a beamforming method based on a deep neural network. Through preprocessing, the space-time domain of the target sound signal is converted into two-dimensional data in the angle-time domain. Subsequently, we trained the network with enough sample datasets. Finally, high-resolution recognition and prediction of two-dimensional images are realized. The results of the test dataset in this paper demonstrate the effectiveness of the proposed method, with a minimum signal-to-noise ratio of -48 dB.

Pneumomediastinum and subcutaneous emphysema secondary to dental extraction: Two case reports.

BACKGROUND: Dental extraction is a common operation in oral surgery and is usually accompanied by pain, swelling, and local infection. The application of high-speed air turbines increases the comfort of alveolar surgery and makes it more minimally-invasive. However, high-speed gas can enter the subcutaneous tissue of the face and neck or even the chest and mediastinum, which is a serious iatrogenic complication. CASE SUMMARY: We describe two cases of severe subcutaneous and mediastinal emphysema caused by high-speed turbine splitting during dental extraction. The first case involved a 34-year-old man who complained of swelling of the face, mild chest tightness, and chest pain after dental extraction. Computed tomography (CT) scan showed a large amount of gas in the neck, chest wall, and mediastinum. The second case involved a 54-year-old woman who complained of swelling and pain of the neck after dental extraction. CT showed a large amount of gas collected in the neck and mediastinum. Both of them used high-speed turbine splitting during dental extraction. CONCLUSION: High-speed turbine splitting during dental extraction may lead to severe subcutaneous and mediastinal emphysema. Dentists should carefully operate to avoid emphysema. If emphysema occurs, CT can be used to improve the diagnosis. The patient should be informed, and the complications dealt with carefully.

Impact of respiratory viral infections on mortality and critical illness among hospitalized patients with chronic obstructive pulmonary disease.

BACKGROUND: Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients. RESEARCH QUESTION: To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients. STUDY DESIGN AND METHODS: We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use. RESULTS: Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza. INTERPRETATION: Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01517191.