Geographic range and minimum infection rate of Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi in Ixodes scapularis (Acari: Ixodidae) ticks in Manitoba, Canada from 1995 to 2017.

INTRODUCTION: The expanding geographical range of blacklegged ticks (BLTs), Ixodes scapularis, and its ability to transmit Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi poses an emerging public health risk. Our study determined the geographic distribution and the minimum infection rate (MIR) of B. burgdorferi-, A. phagocytophilum-, Ba. microti-, and B. miyamotoi-infected BLTs in Manitoba submitted to the Public Health Agency of Canada's passive tick surveillance programme from 1995 to 2017. METHODS: Regression models were used to test the association of the MIR by year for each pathogen. Ticks were tested using PCR for B. burgdorferi since 1995, A. phagocytophilum since 2006, and Ba. microti and B. miyamotoi since 2013. The global positioning system coordinates of infected and uninfected ticks submitted during the surveillance period were plotted on a map of Manitoba using ArcGIS Pro version 3.1.2 to detect changes in the geographic distribution of ticks over time. RESULTS: The overall MIR for B. burgdorferi was 139.7 (95% confidence interval [CI]: 129.0-150.5) per 1000 BLTs; however, it varied over time. After remaining stable from 1995 to 2005, the MIR increased by 12.1 per 1000 BLTs per year from 2005 to 2017 (95% CI: 7.0%-17.2%, p-value <0.01). The geographic distribution of B. burgdorferi-infected BLTs was centred around Winnipeg, Manitoba, and spread outward from this locality. The MIRs of A. phagocytophilum, Ba. microti, and B. miyamotoi were 44.8 per 1000 BLTs (95% CI: 38.1-51.6), 10.8 (95% CI: 6.6-15.0), and 5.2 (95% CI: 2.3-8.1) per 1000 BLTs, respectively, and showed no significant change over time. CONCLUSION: Passive surveillance revealed the presence of A. phagocytophilum-, Ba. microti-, and B. miyamotoi-infected BLTs in southern Manitoba and revealed an increased risk of exposure to B. burgdorferi-infected BLTs due to the increasing geographic range and MIR.

Screening for psychotic experiences and psychotic disorders in general psychiatric settings: a systematic review and meta-analysis.

Background: The absence of systematic screening for psychosis within general psychiatric services contribute to substantial treatment delays and poor long-term outcomes. We conducted a meta-analysis to estimate rates of psychotic experiences, clinical high-risk for psychosis syndrome (CHR-P), and psychotic disorders identified by screening treatment-seeking individuals to inform implementation recommendations for routine psychosis screening in general psychiatric settings. Methods: PubMed and Web of Science databases were searched to identify empirical studies that contained information on the point prevalence of psychotic experiences, CHR-P, or psychotic disorders identified by screening inpatient and outpatient samples aged 12-64 receiving general psychiatric care. Psychotic experiences were identified by meeting threshold scores on validated self-reported questionnaires, and psychotic disorders and CHR-P by gold-standard structured interview assessments. A meta-analysis of each outcome was conducted using the Restricted Maximum Likelihood Estimator method of estimating effect sizes in a random effects model. Results: 41 independent samples (k=36 outpatient) involving n=25,751 patients (58% female, mean age: 24.1 years) were included. Among a general psychiatric population, prevalence of psychotic experiences was 44.3% (95% CI: 35.8-52.8%; 28 samples, n=21,957); CHR-P was 26.4% (95% CI: 20.0-32.7%; 28 samples, n=14,395); and psychotic disorders was 6.6% (95% CI: 3.3-9.8%; 32 samples, n=20,371). Conclusions: High rates of psychotic spectrum illness in general psychiatric settings underscore need for secondary prevention with psychosis screening. These base rates can be used to plan training and resources required to conduct assessments for early detection, as well as build capacity in interventions for CHR-P and early psychosis in non-specialty mental health settings.

Implementation of Community Health Worker Support for Tobacco Cessation: A Mixed-Methods Study.

Objective: Adults with serious mental illness have high tobacco use disorder rates and underutilization of first-line tobacco cessation pharmacotherapy. In a randomized trial, participants offered community health worker (CHW) support and primary care provider (PCP) education had higher tobacco abstinence rates at two years, partly through increased tobacco cessation pharmacotherapy initiation. This study determined the association between participant-CHW engagement and tobacco abstinence outcomes. Methods: This was a secondary, mixed-methods analysis of 196 participants in the trial's intervention arm. Effects of CHW visit number and duration, CHW co-led smoking cessation group sessions attended, and CHW-attended PCP visit number on tobacco use disorder pharmacotherapy initiation and tobacco abstinence were modeled using logistic regression. Interviews with 12 CHWs, 16 participants, and 17 PCPs were analyzed thematically. Results: Year-two tobacco abstinence was associated with CHW visit number (OR=1.85, 95% CI=[1.29, 2.66]) and duration (OR=1.85, 95% CI=[1.33, 2.58]) and number of groups attended (OR=1.51, 95% CI=[1.00, 2.28]); effects on pharmacotherapy initiation were similar. 1-3 CHW visits per month over two years was optimal for achieving abstinence. Interviews identified engagement facilitators, including CHWs establishing trust, providing goal accountability, skills reinforcement, and assistance overcoming barriers to treatment access and adherence related to social determinants of health and illness factors. Robust training and supervision facilitated CHW effectiveness. Barriers included PCPs' and care teams' limited understanding of the CHW role. Conclusions: Feasible CHW engagement was associated with tobacco abstinence in adults with serious mental illness. CHW implementation may benefit from promoting CHW training and integration within clinical teams.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Bloodstream Infections in Children Hospitalized for Influenza, the Canadian Immunization Monitoring Program Active.

BACKGROUND: We aimed to estimate the proportion of children hospitalized for influenza whose illness was complicated by bloodstream infection, describe their clinical course, and identify the factors associated with bloodstream infection. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from the 2010-2011 to 2020-2021 influenza seasons. Factors associated with bloodstream infection were identified using multivariable logistic regression analyses. RESULTS: Among 9179 laboratory-confirmed influenza hospital admissions, bloodstream infection occurred in 87 children (0.9%). Streptococcus pyogenes (22%), Staphylococcus aureus (18%) and Streptococcus pneumoniae (17%) were the most common bloodstream infection pathogens identified. Children with cancer [adjusted odds ratio (aOR): 2.78; 95% confidence interval (CI): 1.23-5.63], a laboratory-confirmed nonbloodstream bacterial infection (aOR: 14.1; 95% CI: 8.04-24.3) or radiographically-confirmed pneumonia (aOR: 1.87; 95% CI: 1.17-2.97) were more likely to experience a bloodstream infection, whereas children with chronic lung disorders were less likely (aOR: 0.41; 95% CI: 0.19-0.80). Disease severity markers such as intensive care unit admission (aOR: 2.11; 95% CI: 1.27-3.46), mechanical ventilation (aOR: 2.84; 95% CI: 1.63-4.80) and longer hospital length of stay (aOR: 1.02; 95% CI: 1.01-1.03) were associated with bloodstream infection. Bloodstream infection also increased the odds of death (aOR: 13.0; 95% CI: 4.84-29.1) after adjustment for age, influenza virus type and the presence of any at-risk chronic condition. CONCLUSIONS: Bloodstream infections, although infrequent, are associated with intensive care unit admission, mechanical ventilation, increased hospital length of stay and in-hospital mortality, thus requiring increased levels of care among pediatric influenza hospitalizations.

COVID-19-related mental health challenges and opportunities perceived by mental health providers in the Philippines.

This paper outlines the psychosocial impacts of the COVID-19 pandemic as reported by 145 licensed mental health providers in the Philippines in an online survey. Respondents perceived an increase in observed mental health disorders in their beneficiaries and an overall decrease in stigma associated with receiving mental health care services during the pandemic. Respondents further identified specific stigma-related help-seeking barriers during the pandemic. Positive impacts of telehealth and importance of increased public education of mental health were highlighted, with implications for improving the landscape of mental health care for Philippines post-pandemic.

Outcomes of immunocompromised children hospitalized for Influenza, 2010-2021, the Canadian Immunization Monitoring Program Active (IMPACT).

OBJECTIVES: To evaluate immunocompromising conditions and subgroups of immunocompromise as risk factors for severe outcomes among children admitted for influenza. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, during 2010-2021. Logistic regression analyses were used to compare outcomes between immunocompromised and non-immunocompromised children, and for different subgroups of immunocompromise. The primary outcome was intensive care unit (ICU) admission; the secondary outcomes were mechanical ventilation and death. RESULTS: Among 8982 children, 892 (9.9%) were immunocompromised; these patients were older (median, 5.6 (IQR, 3.1-10.0) vs. 2.4 (1-6) years; p < 0.001) than non-immunocompromised children, had a similar frequency of comorbidities, excluding immunocompromise and/or malignancy (38% (340/892) vs. 40% (3272/8090); p 0.2), but fewer respiratory symptoms, such as respiratory distress (20% (177/892) vs. 42% (3424/8090), p < 0.001). In multivariable analyses, immunocompromise (adjusted odds ratio (aOR), 0.19; 95% CI, 0.14-0.25) and its subcategories immunodeficiency (aOR, 0.16; 95% CI, 0.10-0.23), immunosuppression (aOR, 0.17; 95% CI, 0.12-0.23), chemotherapy (aOR, 0.07; 95% CI, 0.03-0.13), and solid organ transplantation (aOR, 0.17; 95% CI, 0.06-0.37) were associated with decreased probability of ICU admission in children admitted for influenza. Immunocompromise was also associated with a decreased probability of mechanical ventilation (aOR, 0.26; 95% CI, 0.16-0.38) or death (aOR, 0.22; 95% CI, 0.03-0.72). CONCLUSION: Immunocompromised children are overrepresented among hospitalizations for influenza, but have a decreased probability of ICU admission, mechanical ventilation, and mortality following admission. Admission bias precludes generalizability beyond the hospital setting.

Psychosocial model of burnout among humanitarian aid workers in Bangladesh: role of workplace stressors and emotion coping.

BACKGROUND: While trauma exposure is an established predictor of poor mental health among humanitarian aid workers (HAWs), less is known about the role of psychosocial work-related factors. This study aims to establish a psychosocial model for burnout and psychological distress in HAWs that tests and compares the effects of adversity exposure and workplace stressors in combination, and explores the potential mediating role of individual coping styles. METHODS: Path analysis and model comparison using cross-sectional online survey data were collected from full-time international and local HAWs in Bangladesh between December 2020 and February 2021. HAWs self-reported on exposure to adversities, workplace psychosocial stressors (Third Copenhagen Psychosocial Questionnaire), coping styles (Coping Inventory for Stressful Situations), burnout (Maslach Burnout Inventory-Human Services Survey), and psychological distress (Kessler-6). RESULTS: Among N = 111 HAWs, 30.6%, 16.4%, 12.7%, and 8.2% screened positive for moderate psychological distress (8 ≤ Kessler-6 ≤ 12), emotional exhaustion (EE ≥ 27), depersonalization (DP ≥ 13), and severe psychological distress (K-6 ≥ 13), respectively. 28.8% reported a history of mental disorder. The preferred model showed distinct pathways from adversity exposure and workplace stressors to burnout, with negative emotion-focused coping and psychological distress as significant intervening variables. While greater exposure to both types of stressors were associated with higher levels of burnout and distress, workplace stressors had a stronger association with psychological outcomes than adversity exposure did (ß = .52, p ≤ .001 vs. ß = .20, p = .032). Workplace stressors, but not adversities, directly influenced psychological distress (ß = .45, p ≤ .001 vs. ß = -.01, p = .927). Demographic variables, task-focused and avoidance-focused coping were not significantly associated with psychological outcomes. CONCLUSIONS: Compared to exposure to adversities, workplace stressors primarily influenced occupational stress syndromes. Reducing workplace stressors and enhancing adaptive coping may improve psychological outcomes in humanitarian staff.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

Long-term efficacy of brief psychological treatments for common mental disorders in Myanmar refugees in Malaysia: 12-month follow-up of a randomized, active-controlled trial of integrative adapt therapy v. cognitive behavioral therapy.

BACKGROUND: Long-term efficacy of brief psychotherapies for refugees in low-resource settings is insufficiently understood. Integrative adapt therapy (IAT) is a scalable treatment addressing refugee-specific psychosocial challenges. METHODS: We report 12-month post-treatment data from a single-blind, active-controlled trial (October 2017-August 2019) where 327 Myanmar refugees in Malaysia were assigned to either six sessions of IAT (n = 164) or cognitive behavioral treatment (CBT) (n = 163). Primary outcomes were posttraumatic stress disorder (PTSD), depression, anxiety, and persistent complex bereavement disorder (PCBD) symptom scores at treatment end and 12-month post-treatment. Secondary outcome was functional impairment. RESULTS: 282 (86.2%) participants were retained at 12-month follow-up. For both groups, large treatment effects for common mental disorders (CMD) symptoms were maintained at 12-month post-treatment compared to baseline (d = 0.75-1.13). Although participants in IAT had greater symptom reductions and larger effect sizes than CBT participants for all CMDs at treatment end, there were no significant differences between treatment arms at 12-month post-treatment for PTSD [mean difference: -0.9, 95% CI (-2.5 to 0.6), p = 0.25], depression [mean difference: 0.1, 95% CI (-0.6 to 0.7), p = 0.89), anxiety [mean difference: -0.4, 95% CI (-1.4 to 0.6), p = 0.46], and PCBD [mean difference: -0.6, 95% CI (-3.1 to 1.9), p = 0.65]. CBT participants showed greater improvement in functioning than IAT participants at 12-month post-treatment [mean difference: -2.5, 95% CI (-4.7 to -0.3], p = 0.03]. No adverse effects were recorded for either therapy. CONCLUSIONS: Both IAT and CBT showed sustained treatment gains for CMD symptoms amongst refugees over the 12-month period.

First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.

Zinc-finger nuclease (ZFN)-based in vivo genome editing is a novel treatment that can potentially provide lifelong protein replacement with single intravenous administration. Three first-in-human open-label ascending single-dose phase 1/2 studies were performed in parallel (starting November 2017) primarily to assess safety and tolerability of ZFN in vivo editing therapy in mucopolysaccharidosis I (MPS I) (n = 3), MPS II (n = 9), and hemophilia B (n = 1). Treatment was well tolerated with no serious treatment-related adverse events. At the 1e13 vg/kg dose, evidence of genome editing was detected through albumin-transgene fusion transcripts in liver for MPS II (n = 2) and MPS I (n = 1) subjects. The MPS I subject also had a transient increase in leukocyte iduronidase activity to the lower normal range. At the 5e13 vg/kg dose, one MPS II subject had a transient increase in plasma iduronate-2-sulfatase approaching normal levels and one MPS I subject approached mid-normal levels of leukocyte iduronidase activity with no evidence of genome editing. The hemophilia B subject was not able to decrease use of factor IX concentrate; genome editing could not be assessed. Overall, ZFN in vivo editing therapy had a favorable safety profile with evidence of targeted genome editing in liver, but no long-term enzyme expression in blood.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Pediatric Investigators Collaborative Network on Infections in Canada Study of Respiratory Syncytial Virus-associated Deaths in Pediatric Patients in Canada, 2003-2013.

Background: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are <0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centers. Methods: A retrospective case series of children aged ≤18 years with RSV-associated deaths at centers affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada from 2003­2013, inclusive, was performed [corrected]. Cases were identified using RSV-specific International Classification of Diseases codes to capture deaths where a diagnosis of RSV infection was present. Results: Eleven centers reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range, <1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Healthcare-associated RSV infections (HAIs) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. Conclusions: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs.

Presumed Systemic Inflammatory Response Syndrome in the Pediatric Emergency Department.

OBJECTIVE: The aim of this study was to examine the incidence and outcomes of patients presenting with systemic inflammatory response syndrome (SIRS) in the pediatric emergency department (PED). METHODS: This was a descriptive, retrospective cohort study of all patients from birth to 18 years presenting to the PED of a single center on 16 days distributed over 1 year. The presence of presumed SIRS (pSIRS, defined as noncore temperature measurement and cell count when clinically indicated) and sepsis was determined for all study patients. Patients were followed up for 1 week. RESULTS: The incidence of pSIRS was 15.3% (216/1416). Suspected or proven infection was present in 37.1% (n = 525) of the study population and 76.4% (n = 165) with pSIRS, with no cases of severe sepsis or septic shock. Sensitivity and specificity of pSIRS for predicting infection were 31.4% (95% confidence interval [CI], 27.5%-35.6%) and 94.3% (95% CI, 92.5%-95.7%), respectively. Although patients with pSIRS had a relative risk of 2.4 (95% CI, 1.6-3.5; P < 0.0001) for admission, 74% were discharged home with no subsequent PED visits. Of defined sepsis cases, 75% were discharged home without return. CONCLUSIONS: Presumed SIRS and sepsis are relatively common in the PED. Use of pSIRS to screen for sepsis risks missing infection, whereas using pSIRS in the current sepsis definition results in overinclusion of nonsevere illness.

Improvement of Local Cell Delivery Using Helix Transendocardial Delivery Catheter in a Porcine Heart.

Cardiac regeneration strategies using stem cells have shown variable and inconsistent results with respect to patient cardiac function and clinical outcomes. There has been increasing consensus that improving the efficiency of delivery may improve results. The Helix transendocardial delivery system (BioCardia Inc.) has been developed to enable percutaneous transendocardial biotherapeutic delivery. Therefore, we evaluated cell retention using this unique system compared with direct transepicardial injection and intracoronary infusion in an animal model.Twelve healthy swine were used in this study. 18Fluorodeoxyglucose (FDG)-labeled bone marrow mononuclear cells were delivered via percutaneous transendocardial route using the Helix system (TE group, n = 5), via direct transepicardial injection using a straight 27-gauge needle in an open chest procedure (TP group, n = 4), or via percutaneous intracoronary (IC) infusion (IC group, n = 3). One hour after cell delivery, the distribution of injected cells within the myocardium was assessed by PET-CT. Regions of interest were defined and their signals were compared in each group. Retention rates were calculated as a percentage of the comparing signal.The distribution of injected cells in the myocardium was higher in the TE group (17.9%) than in the TP group (6.0%, versus TE, P < 0.001) and the IC group (1.0%, versus TE, P < 0.001). Consistent with previous reports, there were signal distributions in the lungs, liver, and kidneys in qualitative whole body PET assessment.TE cell delivery using a helical infusion catheter is more efficient in cell retention than either TP delivery or IC delivery using PET-CT analysis.

The trauma signature of 2016 Hurricane Matthew and the psychosocial impact on Haiti.

Background. Hurricane Matthew was the most powerful tropical cyclone of the 2016 Atlantic Basin season, bringing severe impacts to multiple nations including direct landfalls in Cuba, Haiti, Bahamas, and the United States. However, Haiti experienced the greatest loss of life and population disruption. Methods. An established trauma signature (TSIG) methodology was used to examine the psychological consequences of Hurricane Matthew in relation to the distinguishing features of this event. TSIG analyses described the exposures of Haitian citizens to the unique constellation of hazards associated with this tropical cyclone. A hazard profile, a matrix of psychological stressors, and a "trauma signature" summary for the affected population of Haiti - in terms of exposures to hazard, loss, and change - were created specifically for this natural ecological disaster. Results. Hazard characteristics of this event included: deluging rains that triggered mudslides along steep, deforested terrain; battering hurricane winds (Category 4 winds in the "eye-wall" at landfall) that dismantled the built environment and launched projectile debris; flooding "storm surge" that moved ashore and submerged villages on the Tiburon peninsula; and pummeling wave action that destroyed infrastructure along the coastline. Many coastal residents were left defenseless to face the ravages of the storm. Hurricane Matthew's slow forward progress as it remained over super-heated ocean waters added to the duration and degree of the devastation. Added to the havoc of the storm itself, the risks for infectious disease spread, particularly in relation to ongoing epidemics of cholera and Zika, were exacerbated. Conclusions. Hurricane Matthew was a ferocious tropical cyclone whose meteorological characteristics amplified the system's destructive force during the storm's encounter with Haiti, leading to significant mortality, injury, and psychological trauma.