Burden of Severe Illness Associated With Laboratory-Confirmed Influenza in Adults Aged 50-64 Years, 2010-2011 to 2016-2017.

Background: Understanding the burden of influenza is necessary to optimize recommendations for influenza vaccination. We describe the epidemiology of severe influenza in 50- to 64-year-old residents of metropolitan Toronto and Peel region, Canada, over 7 influenza seasons. Methods: Prospective population-based surveillance for hospitalization associated with laboratory-confirmed influenza was conducted from September 2010 to August 2017. Conditions increasing risk of influenza complications were as defined by Canada's National Advisory Committee on Immunization. Age-specific prevalence of medical conditions was estimated using Ontario health administrative data. Population rates were estimated using Statistics Canada data. Results: Over 7 seasons, 1228 hospitalizations occurred in patients aged 50-64 years: 40% due to A(H3N2), 30% A(H1N1), and 22% influenza B. The average annual hospitalization rate was 15.6, 20.9, and 33.2 per 100 000 in patients aged 50-54, 55-59, and 60-64 years, respectively; average annual mortality was 0.9/100 000. Overall, 33% of patients had received current season influenza vaccine; 963 (86%) had ≥1 underlying condition increasing influenza complication risk. The most common underlying medical conditions were chronic lung disease (38%) and diabetes mellitus (31%); 25% of patients were immunocompromised. The average annual hospitalization rate was 6.1/100 000 in those without and 41/100 000 in those with any underlying condition, and highest in those with renal disease or immunocompromise (138 and 281 per 100 000, respectively). The case fatality rate in hospitalized patients was 4.4%; median length of stay was 4 days (interquartile range, 2-8 days). Conclusions: The burden of severe influenza in 50- to 64-year-olds remains significant despite our universal publicly funded vaccination program. These data may assist in improving estimates of the cost-effectiveness of new strategies to reduce this burden.

Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use.

Intravenous and intranasal ketamine have been shown to be effective therapeutic options in patients suffering from treatment-resistant depression (TRD). The use of sublingual (SL), rapid dissolve ketamine tablets (RDT) offers a novel approach for delivery for mental health indications. This study assessed the effectiveness and safety of self-administration of off-label, SL, rapid dissolve ketamine tablets (RDT) at-home for depression and anxiety. Intake scores on the Generalized Anxiety Disorder Screener (GAD-7) and Patient Health Questionnaire (PHQ-9) were compared to scores after treatments of three doses of ketamine RDT, and after six doses of ketamine RDT. After three doses of SL ketamine, 47.6% of patients showed a significant decrease in PHQ-9 scores, and 47.6% of patients showed a significant reduction in GAD-7 scores. Reduction rates were higher in those patients who completed a clinically recommended six doses of RDT ketamine. This study demonstrates that SL ketamine is a novel, safe, and effective treatment for TRD and treatment-resistant anxiety. SL ketamine offers an alternative therapeutic approach to IV ketamine when treating those with TRD.

Graph Eigen Decomposition-Based Feature-Selection Method for Epileptic Seizure Detection Using Electroencephalography.

Epileptic seizure is a sudden alteration of behavior owing to a temporary change in the electrical functioning of the brain. There is an urgent demand for an automatic epilepsy detection system using electroencephalography (EEG) for clinical application. In this paper, the EEG signal is divided into short time frames. Discrete wavelet transform is used to decompose each frame into a number of subbands. Different entropies as well as a group of features with which to characterize the spike events are extracted from each subband signal of an EEG frame. The features extracted from individual subbands are concatenated, yielding a high-dimensional feature vector. A discriminative subset of features is selected from the feature vector using a graph eigen decomposition (GED)-based approach. Thus, the reduced number of features obtained is effective for differentiating the underlying characteristics of EEG signals that indicate seizure events and those that indicate nonseizure events. The GED method ranks the features according to their contribution to correct classification. The selected features are used to classify seizure and nonseizure EEG signals using a feedforward neural network (FfNN). The performance of the proposed method is evaluated by conducting various experiments with a standard dataset obtained from the University of Bonn. The experimental results show that the proposed seizure-detection scheme achieves a classification accuracy of 99.55%, which is higher than that of state-of-the-art methods. The efficiency of FfNN is compared with linear discriminant analysis and support vector machine classifiers, which have classification accuracies of 98.72% and 99.39%, respectively. Hence, the proposed method is confirmed as a potential marker for EEG-based seizure detection.

Mouse Mast Cell Protease-4 Recruits Leukocytes in the Inflammatory Phase of Surgically Wounded Skin.

Objective: Mouse mast cell protease-4 (mMCP-4, also known as chymase) has both pro- and anti-inflammatory roles depending on the disease model. However, its effects have not been studied in surgically wounded skin. Given the significant clinical applications of modulating the inflammatory response in wound healing, we examined the role of mMCP-4 and the effect of its inhibitor chymostatin on leukocyte and polymorphonuclear cell (PMN) recruitment in our skin model. Approach: Recruitment was assessed on day-1 postwounding of three groups of mice (n = 10 each): mMCP-4 null mice, wild-type (WT) mice treated with the mMCP-4 inhibitor chymostatin, and WT with no other intervention. Leukocytes were stained with CD-45 cell marker, and PMN cells were stained with chloroacetate esterase. Results: The WT mice had 27 ± 9 leukocytes per field compared with 11 ± 6 for the mMCP-4 nulls, a decrease of 60% (p = 0.03), whereas the chymostatin-injected group had a count comparable with the uninjected WT controls at 24 ± 9. The WT group had a PMN count of 96 ± 12 cells, compared with just 24 ± 8 in the mMCP-4 null group, a decrease of 75% (p = 0.001), whereas the chymostatin-treated group had 60 ± 18 cells, a decrease of 38% compared with the WT group (p = 0.03). Innovation: We showed that the inflammatory process can be influenced by impeding the arrival of PMNs into the surgically injured site using the mMCP-4 inhibitor chymostatin. Conclusion: Chymase contributes to the recruitment of white blood cells in surgically wounded skin.

Graphene Oxide Liquid Crystal Domains: Quantification and Role in Tailoring Viscoelastic Behavior.

Graphene oxide liquid crystals (GOLCs) were exfoliated in a wide variety of solvents (water, ethylene glycol (EG), N-methyl-2-pyrrolidone (NMP), and dimethylformamide (DMF)) by high-speed shearing of graphite oxide. Quantitative polarized light imaging of the equilibrium nematic phases of the lyotropic GOLCs gives insights into the extent of aggregation and quantifiable textural features such as domain size, d. Large nematic domains >100 µm with a high overall degree of order were obtained in water and ethylene glycol, in contrast to ∼5-50 µm domains in NMP and DMF at comparable volume fractions. Comprehensive rheological studies of these GOLCs indicate that larger domains correlate with higher viscosity and higher elasticity, and scaling analysis shows a power-law dependence of the Ericksen number (Er) with domain size (Er ∝ d3.09). The improved understanding of the relationship between the microstructure and flow properties of GOLCs leads us to an approach of mixed solvent-based GOLCs as a means to tune viscoelastic properties. We demonstrate this approach for the formation of shear-aligned GOLC films for advanced flexible electronic applications such as all-carbon conductive films and thermal heaters.

The Incidence of Hypoglycemia among Insulin-Treated Patients with Type 1 or Type 2 Diabetes: Bangladeshi Cohort of International Operations-Hypoglycemia Assessment Tool Study.

OBJECTIVES: The objective of this study was to assess the incidence of hypoglycemia in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in Bangladeshi cohort of the International Operations-Hypoglycemia Assessment Tool study. MATERIALS AND METHODS: Patients diagnosed with either T1DM or T2DM, aged ≥18 years, treated with insulin (any regimen) for >12 months, and completed self-assessment questionnaires (SAQs) to record demography, treatment information, and hypoglycemia during the 6-month retrospective and 4-week prospective periods (a total of 7 months) were enrolled in the study. RESULTS: A total of 1179 patients were enrolled and completed the SAQ1 (T1DM, n = 25; T2DM, n = 1154). Almost all patients (T1DM: 100.0% [95% confidence interval (CI): 86.3%, 100.0%] and T2DM: 97.0% [95% CI: 95.9%, 97.9%]) experienced at least 1 hypoglycemic event prospectively. The estimated rates of any and severe hypoglycemia were 26.6 (95% CI: 19.8, 35.0) and 14.1 (95% CI: 9.3, 20.4) events per patient-per year (PPY), respectively, for patients with T1DM and 18.3 (95% CI: 17.4, 19.2) and 12.1 (95% CI: 11.4, 12.9) events PPY, respectively, for patients with T2DM during the prospective period. At baseline, mean glycated hemoglobin (HbA1c) (±standard deviation) was 8.1 (±1.8%) for T1DM and 8.8 (±1.8%) for T2DM. Hypoglycemic rate was independent of HbA1c levels and types of insulin. CONCLUSIONS: This is the first patient dataset of self-reported hypoglycemia in Bangladesh; results confirm that hypoglycemia is underreported.

Attempts to minimize nitrogen oxide emission from diesel engine by using antioxidant-treated diesel-biodiesel blend.

The study represents a comprehensive analysis of engine exhaust emission variation from a compression ignition (CI) diesel engine fueled with diesel-biodiesel blends. Biodiesel used in this investigation was produced through transesterification procedure from Moringa oleifera oil. A single cylinder, four-stroke, water-cooled, naturally aspirated diesel engine was used for this purpose. The pollutants from the exhaust of the engine that are monitored in this study are nitrogen oxide (NO), carbon monoxide (CO), hydrocarbon (HC), and smoke opacity. Engine combustion and performance parameters are also measured together with exhaust emission data. Some researchers have reported that the reason for higher NO emission of biodiesel is higher prompt NO formation. The use of antioxidant-treated biodiesel in a diesel engine is a promising approach because antioxidants reduce the formation of free radicals, which are responsible for the formation of prompt NO during combustion. Two different antioxidant additives namely 2,6-di-tert-butyl-4-methylphenol (BHT) and 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (MBEBP) were individually dissolved at a concentration of 1% by volume in MB30 (30% moringa biodiesel with 70% diesel) fuel blend to investigate and compare NO as well as other emissions. The result shows that both antioxidants reduced NO emission significantly; however, HC, CO, and smoke were found slightly higher compared to pure biodiesel blends, but not more than the baseline fuel diesel. The result also shows that both antioxidants were quite effective in reducing peak heat release rate (HRR) and brake-specific fuel consumption (BSFC) as well as improving brake thermal efficiency (BTE) and oxidation stability. Based on this study, antioxidant-treated M. oleifera biodiesel blend (MB30) can be used as a very promising alternative source of fuel in diesel engine without any modifications.

Pre-and post-pandemic trends in antiviral use in hospitalized patients with laboratory-confirmed influenza: 2004/05-2013/14, Toronto, Canada.

BACKGROUND: Data on factors associated with the use of antiviral medication to treat influenza in both children and adults are limited. OBJECTIVES: To describe trends in antiviral use, analyze factors associated with antiviral treatment of hospitalized patients with influenza, and to compare use based on guidelines. STUDY DESIGN: A retrospective observational cohort of hospitalized patients with laboratory confirmed influenza in southern Ontario hospitals for the 2004/05-2013/14 seasons. RESULTS: Of the 7967 patients, 18% of the 1779 children (<15 years) and 66% of the 6188 adults received antiviral therapy. The percentage treated increased from 29% pre-pandemic to 74% during the pandemic, decreased to 55% in 2011/12 and then increased to 65% in 2013/14. Factors significantly associated with antiviral prescription across all age groups during the non-pandemic seasons include influenza type, disease severity, interval between symptom onset and test sample submission, and clinician suspicion of influenza. Rate of treatment of patients meeting guideline criteria was low for children and moderate for adults. CONCLUSIONS: Since the pandemic, there has been a sustained increase in the use of antiviral medication for all age groups of hospitalized patients with influenza, but much higher for adults than children. The odds of treatment are higher for patients with more severe disease as well as for those tested within 48 h of symptom onset, both of which are part of the guidelines for treatment with anti-influenza medications.

Active Surveillance for Influenza Reduces but Does Not Eliminate Hospital Exposure to Patients With Influenza.

OBJECTIVE To describe the frequency, characteristics, and exposure associated with influenza in hospitalized patients in a Toronto hospital DESIGN/METHOD Prospective data collected for consenting patients with laboratory-confirmed influenza and a retrospective review of infection control charts for roommates of cases over 3 influenza seasons RESULTS Of the 661 patients with influenza (age range: 1 week-103 years), 557 were placed on additional precautions upon admission. Of 104 with symptoms detected after admission, 57 cases were community onset and 47 were nosocomial (10 nosocomial were part of outbreaks). A total of 78 cases were detected after admission exposing 143 roommates. Among roommates tested for influenza after exposure, no roommates of community-onset cases and 2 of 16 roommates of nosocomial cases were diagnosed with influenza. Of 637 influenza-infected patients, 25% and 57% met influenza-like illness definitions from the Public Health Agency of Canada (PHAC) and Centers for Disease Control and Prevention (CDC), respectively, and 70.3% met the Provincial Infectious Diseases Advisory Committee (PIDAC) febrile respiratory illness definition. Among the 56 patients with community-onset influenza detected after admission, only 13%, 23%, and 34%, met PHAC, CDC, and PIDAC classifications, respectively. CONCLUSIONS In a setting with extensive screening and testing for influenza, 1 in 6 patients with influenza was not diagnosed until patients and healthcare workers had been exposed for >24 hours. Only 30% of patients with community-onset influenza detected after admission met the Ontario definition intended to identify cases, hampering efforts to prevent patient and healthcare worker exposures and reinforcing the need for prevention through vaccination. Infect Control Hosp Epidemiol 2017;38:387-392.

Induction of Adipogenesis by External Volume Expansion.

BACKGROUND: External volume expansion by suction is used to prepare the recipient site for fat grafting by increasing its compliance and vascularity. The authors previously developed a mouse model for external volume expansion and demonstrated its pro-proliferative and angiogenic effects. Increased thickness of the subcutaneous tissue was also observed. This study was thus designed to assess the adipogenic potential of external volume expansion stimulation. METHODS: A miniaturized external volume expansion device consisting of a rubber dome connected to a -25 mmHg suction source was applied to the dorsum of mice for a single 2-hour stimulation or for 2 hours daily for 5 days. Tissues were harvested up to 48 hours after the last stimulation and analyzed for edema, inflammation, and adipocyte content by staining for hematoxylin and eosin, CD45, and perilipin-A. Expression of peroxisome proliferator-activated receptor-γ (proadipogenic factor) and preadipocyte factor 1 (preadipocyte marker) was evaluated by Western blot analysis. RESULTS: Both a 2-hour stimulation and cyclical 2-hour stimulation for 5 days induced 1.5- and 1.9-fold increases in the number of adipocytes per millimeter. Edema was present in the immediate poststimulation period, and inflammation was seen 2 days later. Peroxisome proliferator-activated receptor-γ was increased at the end of stimulation. CONCLUSIONS: Stretch is known to stimulate proliferation, whereas edema and inflammation are both emerging proadipogenic factors. Their combination in external volume expansion seems to produce proadipogenic effects, seen even after a single 2-hour stimulation.

Respiratory syncytial virus infection-associated hospitalization in adults: a retrospective cohort study.

BACKGROUND: Once considered primarily a pediatric concern, respiratory syncytial virus (RSV) infection is gaining recognition as a cause of significant morbidity and mortality in adults. A better understanding of RSV epidemiology and disease in adults is needed to guide patient management and to assess the need for prophylaxis, vaccines, and treatments. METHODS: We conducted a retrospective cohort study of adults admitted to four hospitals in Toronto, Canada, between September 2012 and June 2013 with RSV identified by a qualitative real-time reverse-transcriptase polymerase chain reaction assay in nasopharyngeal swab or bronchoscopy specimens. Main outcomes were hospital length of stay, need for intensive care unit (ICU) or mechanical ventilation, and all-cause mortality. RESULTS: Eighty-six patients were identified as requiring hospitalization for RSV infection (56% female). Median age was 74 (range 19-102) years; 29 (34%) were < 65 years. Eighty-three (97%) had underlying chronic medical conditions; 27 (31%) were immunosuppressed, and 10 (12%) known smokers. The most common symptoms and signs were cough in 73 (85%), shortness of breath in 68 (79%), sputum production in 54 (63%), weakness in 43 (50%), fever in 41 (48%), and wheezing in 33 (38%). Lower respiratory tract complications occurred in 45 (52%), cardiovascular complications occurred in 19 (22%), and possible co-pathogens were identified in 11 (13%). Sixty-seven (78%) were treated with antibiotics and 31 (36%) with anti-influenza therapy. Thirteen (15%) required ICU care and 8 (9%) required mechanical ventilation. Five (6%) died during hospitalization. Need for ICU and mechanical ventilation were associated with mortality (P ≤ 0.02). Median hospital length of stay was 6 days (mean 10.8 days). CONCLUSIONS: RSV infection is associated with the need for extended hospital stay, ICU care and mortality in adults of all ages with chronic underlying conditions. Presenting signs and symptoms are nonspecific, co-infections occur, and patients often receive antibiotics and anti-influenza therapy. There is need for ongoing research and development of RSV prophylaxis, vaccines and treatments for adults.

Marjolin's ulcer: a preventable malignancy arising from scars.

BACKGROUND: Marjolin's ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy. METHODS: A retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU. RESULTS: An incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = -0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = -0.7, P <0.01). CONCLUSIONS: Patients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.

When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto.

INTRODUCTION: There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection. METHODS: Six Toronto acute care hospitals participated in active surveillance for laboratory-confirmed influenza requiring ICU admission during periods of influenza activity from 2007 to 2009. Nasopharyngeal swabs were obtained from patients who presented to our hospitals with acute respiratory or cardiac illness or febrile illness without a clear nonrespiratory aetiology. Predictors of influenza were assessed by multivariable logistic regression analysis and the likelihood of influenza in different populations was calculated. RESULTS: In 5,482 patients, 126 (2.3%) were found to have influenza. Admission temperature ≥38°C (odds ratio (OR) 4.7 for pH1N1, 2.3 for seasonal influenza) and admission diagnosis of pneumonia or respiratory infection (OR 7.3 for pH1N1, 4.2 for seasonal influenza) were independent predictors for influenza. During the peak weeks of influenza seasons, 17% of afebrile patients and 27% of febrile patients with pneumonia or respiratory infection had influenza. During the second wave of the 2009 pandemic, 26% of afebrile patients and 70% of febrile patients with pneumonia or respiratory infection had influenza. CONCLUSIONS: The findings of our study may assist clinicians in decision making regarding optimal management of adult patients admitted to ICUs during future influenza seasons. Influenza testing, empiric antiviral therapy and empiric infection control precautions should be considered in those patients who are admitted during influenza season with a diagnosis of pneumonia or respiratory infection and are either febrile or admitted during weeks of peak influenza activity.

Evaluation of pneumonia severity and acute physiology scores to predict ICU admission and mortality in patients hospitalized for influenza.

BACKGROUND: The demand for inpatient medical services increases during influenza season. A scoring system capable of identifying influenza patients at low risk death or ICU admission could help clinicians make hospital admission decisions. METHODS: Hospitalized patients with laboratory confirmed influenza were identified over 3 influenza seasons at 25 Ontario hospitals. Each patient was assigned a score for 6 pneumonia severity and 2 sepsis scores using the first data available following their registration in the emergency room. In-hospital mortality and ICU admission were the outcomes. Score performance was assessed using the area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity for identifying low risk patients (risk of outcome <5%). RESULTS: The cohort consisted of 607 adult patients. Mean age was 76 years, 12% of patients died (71/607) and 9% required ICU care (55/607). None of the scores examined demonstrated good discriminatory ability (AUC>or=0.80). The Pneumonia Severity Index (AUC 0.78, 95% CI 0.72-0.83) and the Mortality in Emergency Department Sepsis score (AUC 0.77, 95% 0.71-0.83) demonstrated fair predictive ability (AUC>or=0.70) for in-hospital mortality. The best predictor of ICU admission was SMART-COP (AUC 0.73, 95% CI 0.67-0.79). All other scores were poor predictors (AUC <0.70) of either outcome. If patients classified as low risk for in-hospital mortality using the PSI were discharged, 35% of admissions would have been avoided. CONCLUSIONS: None of the scores studied were good predictors of in-hospital mortality or ICU admission. The PSI and MEDS score were fair predictors of death and if these results are validated, their use could reduce influenza admission rates significantly.