How Does Resorption Differ Among Single-Level and Multilevel Lumbar Disc Herniations? A Prospective Multi-Imaging and Clinical Phenotype Study.

STUDY DESIGN: Prospective, case series. OBJECTIVE: To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH. BACKGROUND: Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations. METHODS: A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH. RESULTS: Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH ( P <0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects ( P =0.001), L4/L5 superior endplate defects ( P =0.012), and L4/L5 inferior endplate defects ( P =0.020) on MRI. No other differences in MRI phenotypes ( e.g. Modic changes, osteophytes, etc .) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH. CONCLUSIONS: Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected. LEVEL OF EVIDENCE: Level 3.

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.

Can clinician's risk assessments distinguish those who disclose suicidal ideation from those who attempt suicide?

Participants were 85 individuals who made suicide attempts within two years of their Improving Access to Psychological Therapies (IAPT) assessment, identified using record linkage. Two comparison groups, non-suicidal controls (n = 1416) and (ideators, n = 743) were compared on variables extracted from the standardized IAPT risk assessment interview. Disclosure of a historical suicide attempt or non-suicidal self-injury (NSSI) distinguished those making an attempt from those with suicidal ideation only, but suicidal intent did not. A third of the participants concealed a historical suicide attempt. The IAPT Phobia Scale classified 49.30% of attempters with 100% specificity. The IAPT Phobia Scale may have clinical value in assessing risk but requires validation. Past suicide attempt and NSSI have better clinical risk assessment utility than current suicidal ideation intensity. Risk assessment relying on disclosure is likely to be flawed and risks support being withheld from those assumed to be at lower risk.

Empiric antibiotics for peripartum bacteremia: A chart review from a quaternary Canadian centre.

OBJECTIVE: To evaluate the effectiveness of empiric antibiotic protocols for peripartum bacteremia at a quaternary institution by describing incidence, microbial epidemiology, clinical source of infection, susceptibility patterns, and maternal and neonatal outcomes. METHODS: Retrospective chart review of peripartum patients with positive blood cultures between 2010 and 2018. RESULTS: The incidence of peripartum bacteremia was 0.3%. The most cultured organisms were Escherichia coli (51, 26.7%), Streptococcus spp. (52, 27.2%), and anaerobic spp. (35, 18.3%). Of the E. coli cases, 54.9% (28), 19.6% (10), and 19.6% (10) were resistant to ampicillin, first- and third-generation cephalosporins, respectively. Clinical sources of infection included intra-amniotic infection/endometritis (115, 67.6%), upper and/or lower urinary tract infection (23, 13.5%), and soft tissue infection (8, 4.7%). Appropriate empiric antibiotics were prescribed in 137 (83.0%) cases. There were 7 ICU admissions (4.2%), 18 pregnancy losses (9.9%), 9 neonatal deaths (5.5%), and 6 cases of neonatal bacteremia (3.7%). CONCLUSION: Peripartum bacteremia remains uncommon but associated with maternal morbidity and neonatal morbidity and mortality. Current empiric antimicrobial protocols at our site remain appropriate, but continuous monitoring of antimicrobial resistance patterns is critical given the presence of pathogens resistant to first-line antibiotics.

Antibiotic use in Canadian neonatal intensive care units: a national survey for developing antimicrobial stewardship targets.

A survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.

Impact of Perinatal Exposure to SARS-CoV-2 Infection on Early Health Outcomes among Infants Born from 2020 to 2021 in British Columbia, Canada.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Investigating the effect of early life antibiotic use on asthma and allergy risk in over 600 000 Canadian children: a protocol for a retrospective cohort study in British Columbia and Manitoba.

INTRODUCTION: Allergic conditions, such as asthma, hay fever and eczema, are some of the most common conditions impacting children globally. There is a strong incentive to study their determinants to improve their prevention. Asthma, hay fever and eczema are influenced through the same immunological pathway and often copresent in children ('the atopic march'). Increasing evidence shows a link between infant antibiotic use and the risk of childhood atopic conditions, mediated through gut microbial dysbiosis during immune system maturation, however, the potential for confounding remains. This study will investigate the relationship between infant antibiotic use and risk of allergic conditions in British Columbian and Manitoban children born over 10 years, adjusting for relevant confounders. METHODS AND ANALYSIS: Provincial administrative datasets will be linked to perform comparable retrospective cohort analyses, using Population Data BC and the Manitoba Population Research Data Repository. All infants born between 2001 and 2011 in BC and Manitoba will be included (approximately 460 000 and 162 500 infants, respectively), following up to age 7. Multivariable logistic regression will determine the outcome risk by the fifth birthday among children who did and did not receive antibiotics before their first birthday. Clinical, demographic and environmental covariates will be explored, and sensitivity analyses performed to reduce confounding by indication. ETHICS AND DISSEMINATION: The University of British Columbia Research Ethics Board (H19-03255) and University of Manitoba Ethics Board (HS25156 (H2021:328)) have approved this study. Data stewardship committees for all administrative datasets have granted permissions, facilitated by Population Data BC and the Manitoba Centre for Health Policy. Permissions from the Canadian Health Infant Longitudinal Development Study are being sought for breastfeeding data (CP185). Findings will be published in scientific journals and presented at infectious disease and respiratory health conferences. A stakeholder committee will guide and enhance sensitive and impactful communication of the findings to new parents.

Penicillin de-labelling in vancouver, British Columbia, Canada: comparison of approaches, outcomes and future directions.

BACKGROUND: Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. METHODS: Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. RESULTS: Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. CONCLUSIONS: Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

OBJECTIVE: To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). DESIGN: Retrospective cohort study between January 1, 2010, and December 31,2019. SETTING: The neonatal intensive care unit at British Columbia Women's Hospital (Vancouver Canada), a tertiary-care center. PATIENTS: Admitted neonates prescribed antibiotics. METHODS: We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. RESULTS: We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. CONCLUSIONS: The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.

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.

Prediction of lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical phenotype study.

BACKGROUND CONTEXT: Symptomatic lumbar disc herniations (LDH) are very common. LDH resorption may occur by a "self-healing" process, however this phenomenon remains poorly understood. By most guidelines, if LDH remains symptomatic after 3 months and conservative management fails, surgical intervention may be an option. PURPOSE: The following prospective study aimed to identify determinants that may predict early versus late LDH resorption. STUDY DESIGN/SETTING: Prospective study with patients recruited at a single center. PATIENT SAMPLE: Ninety-three consecutive patients diagnosed with acute symptomatic LDH were included in this study (n=23 early resorption and n=67 late resorption groups) with a mean age of 48.7±11.9 years. OUTCOMES MEASURE: Baseline assessment of patient demographics (eg, smoking status, height, weight, etc.), herniation characteristics (eg, the initial level of herniation, the direction of herniation, prevalence of multiple herniations, etc.) and MRI phenotypes (eg, Modic changes, end plate abnormalities, disc degeneration, vertebral body dimensions, etc.) were collected for further analysis. Lumbar MRIs were performed approximately every 3 months for 1 year from time of enrollment to assess disc integrity. METHODS: All patients were managed similarly. LDH resorption was classified as early (<3 months) or late (>3 months). A prediction model of pretreatment factors was constructed. RESULTS: No significant differences were noted between groups at any time-point (p>.05). Patients in the early resorption group experienced greater percent reduction of disc herniation between MRI-0-MRI-1 (p=.043), reduction of herniation size for total study duration (p=.007), and percent resorption per day compared to the late resorption group (p<.001). Based on multivariate modeling, greater L4 posterior vertebral height (coeff:14.58), greater sacral slope (coeff:0.12), and greater herniated volume (coeff:0.013) at baseline were found to be most predictive of early resorption (p<.05). CONCLUSIONS: This is the first comprehensive imaging and clinical phenotypic prospective study, to our knowledge, that has identified distinct determinants for early LDH resorption. Early resorption can occur in 24.7% of LDH patients. We developed a prediction model for early resorption which demonstrated great overall performance according to pretreatment measures of herniation size, L4 posterior body height, and sacral slope. A risk profile is proposed which may aid clinical decision-making and managing patient expectations.

Variability in antimicrobial use among infants born at <33 weeks gestational age.

Excessive antimicrobial use is associated with adverse neonatal outcomes. In our cohort of 27,163 infants born at <33 weeks gestational age, the first week after birth accounted for the highest rates of antimicrobial use, and variability across sites persisted after adjustment for patient characteristics correlated with illness severity.

A Pediatric Investigators Collaborative Network on Infections in Children (PICNIC) multi-centre Canadian descriptive analysis of Haemophilus influenzae bacteremia in children: Emerging serotypes.

Background: There has been dramatic reduction in Haemophilus influenzae serotype b (Hib) since introduction of Hib vaccines, but children still experience serious invasive Haemophilus influenzae (Hi) disease caused by various serotype and non-typeable bacteria. The object of this study was to describe the serotype distribution and clinical spectrum of Hi bacteremia in children admitted to Canadian hospitals. Methods: All children with Hi bacteremia admitted 2013 through 2017 to 10 centres across Canada were included. Demographic, clinical, treatment and outcome data were collected. Results: Haemophilus influenzae bacteremia occurred in 118 children of median age 12 months (inter-quartile range: 7-48 months). Forty-three (36%) isolates were non-typeable (NTHi) and 8 were not typed. Of the 67 typeable (THi), Hia (H. influenzae serotype a) (n=36, 54%), Hif (serotype f) (n=19, 26%) and Hib (serotype b) (n=9, 13%) dominated. The THi was more likely than NTHi bacteremia to present as meningitis (p<0.001), particularly serotype a (p=0.04) and less likely to present as pneumonia (p<0.001). Complicated disease (defined as intensive care unit admission, need for surgery, long-term sequelae or death) occurred in 31 (26%) cases and were more likely to have meningitis (p<0.001) than were those with uncomplicated disease. Conclusion: In the era of efficacious conjugate Hib vaccines, NTHi, Hia and Hif have emerged as the leading causes of invasive Hi in Canadian children, with Hia being most likely to result in meningitis and complicated disease. A vaccine for all NTHi and THi would be ideal, but knowledge of the current disease burden from circulating strains will inform prioritization of vaccine targets.

Establishing obstetrics-specific metrics and interventions for antimicrobial stewardship.

Background: To describe baseline antimicrobial stewardship (AMS) metrics and apply AMS interventions in an inpatient obstetrical population. Methods: From October 2018 to October 2019, our tertiary-care obstetrical center reviewed components of our AMS program, which included: (1) antimicrobial consumption data, (2) point prevalence surveys (PPS), and (3) prospective audit and feedback. We reviewed institutional data for antimicrobial consumption from the pharmacy database. Detailed point prevalence surveys were conducted for all antimicrobial prescriptions on two predefined dates each month. Daily audits and feedback assessed the appropriateness of all non-protocolized antimicrobials. Results: Our average antimicrobial length of therapy (LOT) was 12 days per 100 patient-days, where erythromycin (2.33), amoxicillin (2.28), and ampicillin (1.81) were the greatest contributors. Point prevalence surveys revealed that 28.8% of obstetrical inpatients were on antimicrobials, of which 11.2% were inappropriate. Protocolized antimicrobials were 62% less likely (p = 0.027) to be inappropriate. From 565 audited prescriptions, 110 (19.5%) resulted in feedback, where 90% of recommendations were accepted and implemented. The most common reasons for interventions include incorrect dosage, recommending a diagnostic test before continuing antimicrobials, and changing antimicrobials based on specific culture and sensitivity. Conclusions: Antimicrobial use in obstetrics is unique compared to general inpatients. We provide a baseline set of metrics for AMS at our obstetrical center intending to lay the groundwork for AMS programming in our discipline. Antimicrobial protocolization, as well as audit and feedback, are feasible interventions to improve antimicrobial prescribing patterns.

Historique: Décrire les mesures de gouvernance antimicrobienne (GAM) fondamentales et utiliser les interventions de GAM dans une population obstétricale hospitalisée. Méthodologie: D'octobre 2018 à octobre 2019, le centre obstétrical de soins tertiaires a révisé les éléments du programme de GAM, qui incluait : 1) les données sur la consommation d'antimicrobiens, 2) les enquêtes de prévalence ponctuelles (EPP) et 3) la vérification et la rétroaction prospectives. Les chercheurs ont examiné les données institutionnelles relatives à la consommation d'antimicrobiens dans la base de données de la pharmacie. Ils ont effectué des enquêtes de prévalence ponctuelles détaillées sur toutes les prescriptions d'antimicrobiens à deux dates déterminées chaque mois. Les vérifications et les rétroactions quotidiennes ont permis d'évaluer la pertinence de tous les antimicrobiens non protocolisés. Résultats: La durée du traitement antimicrobien moyen était de 12 jours sur 100 jours-patients, et l'érythromycine (2,33), l'amoxicilline (2,28) et l'ampicilline (1,81) étaient les plus utilisées. Les enquêtes de prévalence ponctuelles ont révélé que 28,8 % des patientes obstétricales hospitalisées prenaient des antimicrobiens, dont 11,2 % étaient inappropriés. Les antimicrobiens protocolisés étaient 62 % moins susceptibles d'être inappropriés (p = 0,027). Des 565 prescriptions vérifiées, 110 (19,5 %) ont donné lieu à des rétroactions, et 90 % des recommandations ont été acceptées et mises en œuvre. Les principales raisons d'intervenir incluaient une posologie inexacte, la recommandation d'un test diagnostique avant de poursuivre l'antimicrobien, ainsi que le changement d'antimicrobien d'après la culture et sensibilité spécifiques. Conclusions: L'utilisation d'antimicrobiens est unique en obstétrique par rapport aux autres patients hospitalisés. Les chercheurs fournissent la série de mesures de GAM de référence utilisée à leur centre obstétrical pour jeter les bases de la programmation de la GAM dans la discipline. La protocolisation des antimicrobiens, de même que la vérification et la rétroaction, est une intervention faisable pour améliorer les profils de prescription d'antimicrobiens.

Risk factors associated with palbociclib-induced neutropenia in patients with metastatic breast cancer.

BACKGROUND: Neutropenia is the most common adverse event with palbociclib, an oral cyclin-dependent kinase 4/6 inhibitor, with grade 3/4 neutropenia occurring in up to 67% of patients in phase III trials evaluating this agent in metastatic breast cancer. This retrospective chart review assessed characteristics of patients on palbociclib to evaluate for risk factors in the development of grade 3/4 neutropenia. PATIENTS AND METHODS: Patients with metastatic breast cancer who received palbociclib were included. Patient demographics collected included age, gender, race, body mass index, breast cancer treatment history, palbociclib starting dose, baseline absolute neutrophil count, baseline platelet count, concomitant hormonal therapy, concomitant use of denosumab, and use of concomitant strong CYP3A4 inhibitors/inducers. Events of interest occurring within 30 days of initiation of palbociclib were also noted including antibiotic and corticosteroid use, mucosal conditions, open wounds, or surgery. The incidence and potential risk factors for grade 3/4 neutropenia in the first 6 months of treatment were analyzed. RESULTS: A total of 257 patients were included in the analysis with 206 patients (80.2%) and 139 patients (54.1%) experiencing all-grade neutropenia and grade 3/4 neutropenia, respectively. Multivariate analysis found baseline myelosuppression and recent antibiotic use to be independent predictors of grade 3/4 neutropenia. Normal weight patients had an increased risk for grade 3/4 neutropenia compared to obese patients by multivariate analysis. CONCLUSION: The results of this study showed baseline myelosuppression and recent antibiotic use within 30 days of palbociclib initiation were predictive of a higher incidence of grade 3/4 neutropenia. Obese patients were less likely to develop grade 3/4 neutropenia compared to normal weight patients.

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.

Practice Summary of Antimicrobial Therapy for Commonly Encountered Conditions in the Neonatal Intensive Care Unit: A Canadian Perspective.

Neonates are highly susceptible to infections owing to their immature cellular and humoral immune functions, as well the need for invasive devices. There is a wide practice variation in the choice and duration of antimicrobial treatment, even for relatively common conditions in the NICU, attributed to the lack of evidence-based guidelines. Early decisive treatment with broad-spectrum antimicrobials is the preferred clinical choice for treating sick infants with possible bacterial infection. Prolonged antimicrobial exposure among infants without clear indications has been associated with adverse neonatal outcomes and increased drug resistance. Herein, we review and summarize the best practices from the existing literature regarding antimicrobial use in commonly encountered conditions in neonates.

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.