Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study.

OBJECTIVE: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections. DESIGN: Multi-centre observational cohort study using data from 2009 to 2018 clinical records. SETTING: Canadian children's hospitals (7) and community hospitals (3). PATIENTS: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections. INTERVENTIONS: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation. MAIN OUTCOME MEASURES: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates. RESULTS: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018. CONCLUSIONS: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.

A Canadian children's hospital's experience with cystic echinococcosis over 30 years: A case series.

Background: Cystic echinococcosis (CE) or hydatid disease caused by the cestode Echinococcus granulosus sensu lato is an uncommon infection in Canada especially among children. There are limited reports describing the clinical presentation and management in Canadian children. Methods: The medical records of all children diagnosed with CE at a quaternary paediatric centre in Ontario between January 1988 and August 2021 were retrospectively reviewed. The clinical course, management, and outcomes of each case were summarized. Results: We report two paediatric cases of cystic echinococcosis (CE) in detail and review four additional cases seen at our institution over 33.5 years. The first case was a previously healthy 12-year-old boy with pulmonary CE resulting in unilateral lung collapse and mediastinal shift, who was presumedly infected while living in the Middle East. The second case was a previously healthy 3-year-old girl with pulmonary CE acquired locally in southern Ontario. Four other cases of CE with hepatic involvement (median age 12.5 years) were identified during the study period. Five out of six patients received both surgical and medical therapy. Conclusion: CE is a rare but serious disease seen in southern Canada that has historically been associated with travel or migration. Due to changes in urban wildlife landscapes and increased global migration, CE may become more prevalent in Canadian children. We describe the first locally acquired case in rural southern Ontario diagnosed at our centre. Prompt recognition of this infection in children by health care providers is important to prevent morbidity and mortality.

Historique: L'échinococcose kystique (ÉK), ou hydatidose, causée par le cestode Echinococcus granulosus sensu lato, est une infection peu courante au Canada, particulièrement chez les enfants. Peu de rapports en décrivent la présentation clinique et la prise en charge chez les enfants canadiens. Méthodologie: Les auteurs ont procédé à l'analyse rétrospective des dossiers médicaux de tous les enfants ayant reçu un diagnostic d'ÉK dans un centre pédiatrique de soins quaternaires ontarien entre janvier 1988 et août 2021. Ils ont résumé l'évolution clinique, la prise en charge et le résultat clinique de chaque cas. Résultats: Les auteurs font un compte rendu détaillé de deux cas pédiatriques d'ÉK et analysent quatre autres cas observés à leur établissement sur une période de 33,5 ans. Le premier cas d'ÉK pulmonaire a touché un garçon de 12 ans auparavant en santé, probablement infecté alors qu'il habitait au Moyen-Orient, et a entraîné un collapsus pulmonaire unilatéral et une déviation médiastinale. Le deuxième cas d'ÉK pulmonaire a été observé chez une fillette de trois ans auparavant en santé qui a été infectée dans le sud de l'Ontario. Les auteurs ont relevé quatre autres cas d'ÉK comportant une atteinte hépatique (âge médian de 12,5 ans) pendant la période de l'étude. Cinq des six patients ont reçu à la fois un traitement chirurgical et médical. Conclusion: L'ÉK est une maladie rare, mais grave dans le sud du Canada. Elle était auparavant associée à un voyage ou une migration. En raison des changements aux paysages fauniques urbains et de la migration mondiale accrue, elle pourrait devenir plus prévalente chez les enfants canadiens. Les auteurs décrivent les premiers cas d'acquisition dans les régions rurales du sud de l'Ontario, diagnostiqués à leur centre. Il est important que les dispensateurs de soins dépistent cette infection rapidement chez les enfants pour éviter la morbidité et la mortalité.

The long and the short of pediatric emergency department antibiotic prescribing: A retrospective observational study.

BACKGROUND: Most antibiotics prescribed to children are provided in the outpatient and emergency department (ED) settings, yet these prescribers are seldom engaged by antibiotic stewardship programs. We reviewed ED antibiotic prescriptions for three common infections to describe current prescribing practices. METHODS: Prescription data between 2018 and 2021 were extracted from the electronic records of children discharged from the Children's Hospital of Eastern Ontario ED with urinary tract infection (UTI), community acquired pneumonia (CAP), and acute otitis media ≥2 years of age (AOM). Antibiotic choice, duration, as well as the provider's time in practice and training background were collected. Antibiotic durations were compared with Canadian guideline recommendations to assess concordance. Provider-level prescribing practices were analyzed using k-means cluster analysis. RESULTS: 10,609 prescriptions were included: 2868 for UTI, 2958 for CAP, and 4783 for AOM. Guideline-concordant durations prescribed was generally high (UTI 84.9%, CAP 94.0%, AOM 52.8%), a large proportion of antibiotic-days prescribed were in excess of the minimally recommended duration for each infection (UTI 16.8%, 19.3%, AOM 25.5%). Cluster analysis yielded two clusters of prescribers, with those in one cluster more commonly prescribing durations at the lower end of recommended interval, and the others more commonly prescribing longer durations for all three infections reviewed. No statistically significant differences were found between clusters by career stage or training background. CONCLUSIONS: While guideline-concordant antibiotic prescribing was generally high, auditing antibiotic prescriptions identified shifting prescribing towards the minimally recommended duration as a potential opportunity to reduce antibiotic use among children for these infections.

Robinsoniella peoriensis: An emerging pathogen and rare cause of wound infection in children.

BACKGROUND: Robinsoniella peoriensis is an anaerobic gram-positive bacilli first isolated from swine manure in 2003 but has since been associated with human infections. METHODS: We describe a pediatric case of R. peoriensis infection following a below-knee amputation for a limb injury and its treatment. Methods of identifying R. peoriensis and reported in vitro antimicrobial minimum inhibitory concentrations from the literature are reviewed. RESULTS: R. peoriensis is readily identifiable via 16S rRNA gene sequencing and Matrix-Assisted Laser Desorption Ionization-Time of Flight. There is variability in the antibiotic susceptibility profiles reported in the literature, but antibiotics with low in vitro minimum inhibitor concentrations against R. peoriensis include beta-lactam/beta-lactamase inhibitors, carbapenems, vancomycin, and metronidazole. CONCLUSION: This is the first reported case of R. peoriensis infection following a traumatic injury in Canada to our knowledge and highlights the importance of recognizing this organism and other anaerobes in settings where wounds are grossly contaminated with soil.

HISTORIQUE: Le Robinsoniella peoriensis est un bacille anaérobie à Gram positif d'abord isolé en 2003 dans le lisier de porc, mais qui a été associé à des infections humaines depuis. MÉTHODOLOGIE: Les auteurs décrivent un cas pédiatrique d'infection à R. peoriensis après une amputation au-dessous du genou à cause de la lésion d'un membre et de son traitement. Les chercheurs ont examiné les méthodes pour identifier le R. peoriensis et les concentrations minimales inhibitrices antimicrobiennes in vitro tirées des publications. RÉSULTATS: Le R. peoriensis est facile à identifier au moyen du séquençage du gène d'ARNr 16S et du spectromètre de masse à temps de vol pour la désorption-ionisation laser assistée par matrice. La description des profils de susceptibilité des antibiotiques est variable selon les publications, mais les antibiotiques aux concentrations minimales inhibitrices contre le R. peoriensis sont les bêta-lactamines et les inhibiteurs de bêta-lactamase, les carbapénems, la vancomycine et le métronidazole. CONCLUSION: À la connaissance des auteurs, il s'agit du premier cas déclaré d'infection à R. peoriensis après une lésion traumatique au Canada, ce qui fait ressortir l'importance de tenir compte de cet organisme et d'autres anaérobies lorsque les plaies sont grandement contaminées par de la terre.

Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review.

BACKGROUND: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. METHODS: This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. FINDINGS: We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. CONCLUSIONS: The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

Changes in the Management of Severe Orbital Infections Over Seventeen Years.

OBJECTIVES: Periorbital and orbital cellulitis are common but serious infections in children. Management of these infections varies because of an absence of clinical guidelines, but it is unclear if management within institutions has changed over time. We compared the management and outcomes of children hospitalized with periorbital and orbital cellulitis in 2 eras. METHODS: Data were extracted from records of children hospitalized at a tertiary care children's hospital with periorbital or orbital cellulitis from 2000 to 2005 and 2012 to 2016. Patient demographics, cross-sectional imaging, antibiotic and corticosteroid use, length of stay, and surgical rates were collected. Data from the eras were compared by using descriptive statistics, t tests, Mann-Whitney U tests, Fisher's exact tests, and χ2 tests. RESULTS: There were 318 children included, 143 from 2000 to 2005 and 175 from 2012 to 2016. Compared with the first era, in the second era there were increased rates of MRI (5% vs 11%, P = .04), although rates of computed tomography scan use remained unchanged (60% vs 65%); increased number (1 vs 3, P < .01) and spectrum of antibiotics; increased use of intranasal corticosteroids (3% vs 49%, P < .01); and subspecialty consultation (89% vs 99%, P = .01). There were no differences in length of stay, readmission, or surgical rates between eras. CONCLUSIONS: There has been considerable change in the management of hospitalized children with severe orbital infections at our institution, including the rates of MRI, number and spectrum of antibiotics used, use of adjunctive agents, and increased subspecialty involvement with no observed impact on clinical outcomes. Future research is needed to rationalize antimicrobial therapy and reduce low-value health care.

The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide.

BACKGROUND: The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. METHODS: To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0-19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). RESULTS: We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). CONCLUSIONS: The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

A Retrospective Review of Physician-related Patient Complaints from a Tertiary Pediatric Hospital.

BACKGROUND: Trends in patient concerns can identify systematic problems in health care delivery that may not be detected when addressing individual concerns. It can be difficult identifying trends without using a standardized taxonomy. The study objectives were to describe patient complaints from a tertiary care pediatric hospital and categorize them using a standardized complaint taxonomy. METHODS: Physician-based patient complaints were compiled from April 2011 to May 2014 from a tertiary pediatric hospital. These complaints were coded independently by 2 reviewers using the Reader taxonomy, a published standardized taxonomy. Complaints were placed into 3 domains: clinical, management, and relationships then organized into categories. Inter-rater reliability for domain classification between the 2 reviewers was calculated using Cohen's unweighted κ. RESULTS: Eighty-seven patient complaints were identified, representing approximately 1 per 10,000 physician-patient encounters. Half (48/87) were related to care in the emergency department. When adjusted for volume, pediatric hospital medicine had the highest number of complaints, with 12.1 per 10,000 encounters. The majority of patient complaints, 66% (57/87), were of the clinical domain (κ = 0.61). Sixty percent (52/87) were in the relationship domain (κ = 0.68), and 16% (14/87) were in the management domain (κ = 0.65). CONCLUSIONS: We found a low overall complaint rate. Our results indicate that interventions to improve patient experience should initially be targeted at emergency and hospital medicine on the clinical and relationship domains. The inter-rater reliability of the Reader taxonomy was moderate with implications for processing patient complaints at a hospital level.

Impacts of genetic correlation on the independent evolution of body mass and skeletal size in mammals.

BACKGROUND: Mammals show a predictable scaling relationship between limb bone size and body mass. This relationship has a genetic basis which likely evolved via natural selection, but it is unclear how much the genetic correlation between these traits in turn impacts their capacity to evolve independently. We selectively bred laboratory mice for increases in tibia length independent of body mass, to test the hypothesis that a genetic correlation with body mass constrains evolutionary change in tibia length. RESULTS: Over 14 generations, we produced mean tibia length increases of 9-13%, while mean body mass was unchanged, in selectively bred mice and random-bred controls. Using evolutionary scenarios with different selection and quantitative genetic parameters, we also found that this genetic correlation impedes the rate of evolutionary change in both traits, slowing increases in tibia length while preventing decreases in body mass, despite the latter's negative effect on fitness. CONCLUSIONS: Overall, results from this ongoing selection experiment suggest that parallel evolution of relatively longer hind limbs among rodents, for example in the context of strong competition for resources and niche partitioning in heterogeneous environments, may have occurred very rapidly on geological timescales, in spite of a moderately strong genetic correlation between tibia length and body mass.

Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure.

BACKGROUND: The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. METHODS AND RESULTS: Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I-III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. CONCLUSION: Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF.

Role of nonsustained ventricular tachycardia and programmed ventricular stimulation for risk stratification in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The prognostic role of asymptomatic nonsustained ventricular tachycardia (NSVT) and programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (IDC) remains controversial. METHODS: The prognostic significance of ventricular arrhythmias, ejection fraction, NYHA class, atrial fibrillation and age for overall and sudden death mortality was prospectively studied in 157 patients with IDC (group 1) free of documented sustained ventricular arrhythmia and syncope. In 99 patients with asymptomatic NSVT (group 2), PVS with 2 - 3 extrastimuli was performed. Non-inducible patients were discharged without specific antiarrhythmic therapy, whereas those with inducible monomorphic ventricular tachycardia were implanted with an ICD. RESULTS: In group 1, 48% of patients had NSVT. Overall and sudden death mortality were significantly higher in patients with NSVT (34.2 vs. 9.8%, p = 0.0001 and 15.8 vs. 3.7%, p = 0.0037; follow-up 22 +/- 14 months). Multivariate analysis revealed that NSVT independently predicts both overall and sudden death mortality (p = 0.0021 and.0221, respectively; adjusted for EF, NYHA class and age). In group 2, inducibility of sustained ventricular tachyarrhythmia was 7%, but sustained monomorphic VT occurred in 3% only. Two of 7 inducible patients experienced arrhythmic events during a follow-up of 25 +/- 21 months (positive predictive value 29%). Overall and sudden death mortality were 29% and 0% in the inducible group vs. 17 and 4% in the non-inducible group. Both overall and sudden death mortality were significantly lower in non-inducible patients from group 2 as compared to patients from group 1 with NSVT (p = 0.0043 and 0.0048), most likely due to a more common use of betablockers and a higher EF in the former group (p < 0.001, respectively). CONCLUSIONS: In patients with IDC, NSVT independently predicts both overall and sudden death mortality. Due to a low inducibility rate and a poor positive predictive value, PVS seems inappropriate for further arrhythmia risk assessment. However, in spite of documented NSVT, the incidence of SCD in patients on optimized medical treatment including betablockers seems to be very low, questioning the need for specific arrhythmia risk stratification.