Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

Second malignant neoplasms within 5 years from first primary diagnosis in pediatric oncology patients in Canada: a population-based retrospective cohort study.

Introduction: From the advancement of treatment of pediatric cancer diagnosis, the five-year survival rate has increased significantly. However, the adverse consequence of improved survival rate is the second malignant neoplasm. Although previous studies provided information on the incidence and risk of SMN in long term survivors of childhood cancer, there is still scarce information known for short term (< 5 years) prognosis. This study aims to assess the incidence, characteristics, management, and outcome of children who develop SMN malignancies within 5 years of diagnosis of their initial cancer. Method: This is a retrospective cohort study of early Second Malignant Neoplasms (SMN) in pediatric oncology patients. The Cancer in Young People - Canada (CYP-C) national pediatric cancer registry was used and reviewed pediatric patients diagnosed with their first cancer from 2000-2015. Results: A total of 20,272 pediatric patients with a diagnosis of a first malignancy were analyzed. Of them, 0.7% were diagnosed with a SMN within the first 5 years following their first cancer diagnosis. Development of a SMN impacted survival, shown by an inferior survival rate in the SMN cohort (79.1%) after three years compared to that of the non-SMN cohort (89.7%). Several possible risk factors have been identified in the study including the use of epipodophyllotoxins, exposure to radiation, and hematopoietic stem cell 169 transplant. Discussion: This is the first national study assessing the incidence, 170 characteristics, risk factors and outcome of early SMN in Canadian children 171 from age 0-15 from 2000-2015.

Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

Bacterial heat shock protein genes during induction chemotherapy in pediatric patients with acute lymphoblastic leukemia.

Background: Heat shock proteins (HSP) protect cancer cells. Gastrointestinal bacteria contain HSP genes and can release extracellular vesicles which act as biological shuttles. Stress from treatment may result in a microbial community with more HSP genes, which could contribute to circulating HSP levels. Methods: The authors examined the abundance of five bacterial HSP genes pre-treatment and during induction in stool sequences from 30 pediatric acute lymphoblastic leukemia patients. Results: Decreased mean HTPG counts (p = 0.0024) pre-treatment versus induction were observed. During induction, HTPG, Shannon diversity and Bacteroidetes decreased (p = 7.5e-4; 1.1e-3; 8.6e-4), while DNAK and Firmicutes increased (p = 6.9e-3; 9.2e-4). Conclusion: Understanding microbial HSP gene community changes with treatment is the first step in determining if bacterial HSPs are important to the tumor microenvironment and leukemia treatment.

Validation of co-Symptom Screening in Pediatrics Tool: a novel dyadic approach to symptom screening in pediatric patients receiving cancer treatment.

BACKGROUND: Co-Symptom Screening in Pediatrics Tool (co-SSPedi) is a dyadic (child-guardian) approach to symptom assessment. Objectives were to evaluate the reliability and validity of co-SSPedi for pediatric patients receiving cancer treatments. METHODS: This multicenter study included dyads of patients aged 4-18 years of age with cancer or undergoing hematopoietic cell transplant and their guardians. Two groups were enrolled. The more symptomatic group included those receiving active treatment for cancer or undergoing hematopoietic cell transplant where patients were in hospital or clinic for 4 consecutive days. The less symptomatic group included those receiving maintenance therapy for acute lymphoblastic leukemia or who had completed cancer treatments. At baseline, all dyads completed co-SSPedi, and guardians completed measures of mucositis, nausea, pain, quality of life, and overall symptoms. In the more symptomatic group, dyads completed co-SSPedi and a global symptom change scale on day 4. RESULTS: There were 501 dyads included: 301 in the more symptomatic group and 200 in the less symptomatic group. Median time to complete co-SSPedi was less than 3 minutes in both groups. Test-retest reliability intraclass correlation coefficient was 0.85 (95% confidence interval [CI] = 0.77 to 0.90). For internal consistency, total co-SSPedi Cronbach alpha was 0.81 (95% CI = 0.78 to 0.83). For known groups validation, mean difference in total co-SSPedi scores between the more symptomatic and less symptomatic groups was 7.8 (95% CI = 6.7 to 8.8; P < .0001). For convergent validation and responsiveness, all hypothesized relationships were demonstrated. CONCLUSIONS: Co-SSPedi is a novel approach to dyadic symptom assessment that is reliable, valid, and responsive in pediatric patients aged 4-18 years.

Accuracy of reticulocyte hemoglobin for diagnosing iron deficiency in former very preterm infants: a population-based cohort study.

Background: Serum ferritin (SF) is commonly used to diagnose iron deficiency (ID) but has limitations. Reticulocyte hemoglobin (Ret-He) is being increasingly used for ID diagnosis. This study aimed to assess accuracy of Ret-He for ID diagnosis in former very preterm infants (VPI) at 4-6 months corrected age (CA). Methods: A retrospective population-based cohort study was conducted on all live VPI born between 23 and 30 weeks of gestational age (GA) in Nova Scotia from 2012 to 2018. Infants underwent SF and Ret-He testing at 4-6 months CA. ID was defined using two definitions. The first defined ID as SF < 20 mcg/L at both 4- and 6-months CA, and the second as SF < 30 mcg at at both 4- and 6-months CA. The accuracy of Ret-He for identifying ID was assessed using the area under the receiver operating characteristic curve (AUC). Results: ID was present in 39.7% (62) of 156 infants in the first definition and 59.6% (93) in the second at 4-6 months CA. The AUC of Ret-He for ID diagnosis was 0.64 (p = 0.002) in the first definition and 0.59 (p = 0.04) in the second. The optimal cut-off was 29.4pg in the first and 29.7 in the second definition. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) at the 29.4 pg cut-off were 50.0%, 78.7%, 60.8%, and 70.5% for definition 1 and 44.1%, 74.6%, 71.9%, and 47.5% at the 29.7pg cut-off for definition 2. Conclusion: Ret-He had low diagnostic accuracy for ID diagnosis in former VPI. Caution is advised when using Ret-He alone for ID diagnosis. Further research is needed to establish optimal approaches for identifying ID in VPI.

A Case of Modified McLaughlin Procedure in Neglected Posterior Shoulder Fracture Dislocation.

A Hill-Sachs lesion, a posterolateral bony defect of the proximal humerus, occurs when the humerus head collides with the anterior region of the glenoid during an anterior shoulder dislocation. A posteriorly dislocated shoulder may cause a reverse Hill-Sachs lesion, which is a deficiency on the anteromedial part of the humeral head due to impaction. Avascular necrosis could result from this lesion if detection and repair are not carried out. The subscapularis tendon is separated from the smaller tuberosity using an open technique in the original McLaughlin procedure, which was initially described in 1952. In neglected cases of patients undergoing surgery after three weeks, there is no commonly accepted standard of care. Glenohumeral joint stabilization and early and full functional recovery are the two objectives of the procedure. This case report describes a modified McLaughlin surgery where the subscapularis tendon and lesser tuberosity are transferred to the reverse Hill-Sachs defect for stability. The clinical significance of our case report is that it accentuates the role of early detection and appropriate management of reverse Hill-Sachs lesion, which is often overlooked and missed in a case of posterior shoulder dislocation. The use of the modified McLaughlin procedure not only covers the defect with a bone chunk and the subscapularis tendon transfer over the head of the humerus but the stable fixation with the anchor and cannulated cancellous screw helps in early rehabilitation of the shoulder joint.

The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients.

Introduction: Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include ß-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. Methods: We examined the impact of repeated courses and duration of antibiotic use on the resistome of 39 pediatric leukemia and lymphoma patients. Shotgun metagenome sequences from 127 stool samples of pediatric oncology patients were examined for abundance of antibiotic resistance genes (ARGs) in each sample. Abundances were grouped by repeated courses (no antibiotics, 1-2 courses, 3+ courses) and duration (no use, short duration, long and/or mixed durationg) of ß-lactams, vancomycin and "any antibiotic" use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. Results: We found that Bacteroidetes taxa and ß-lactam resistance genes decreased, while opportunistic Firmicutes and Proteobacteria taxa, along with multidrug resistance genes, increased with repeated courses and/or duration of antibiotics. Efflux pump related genes predominated (92%) among the increased multidrug genes. While we found ß-lactam ARGs present in the resistome, the taxa that appear to contain them were kept in check by antibiotic treatment. Multidrug ARGs, mostly efflux pumps or regulators of efflux pump genes, were associated with opportunistic pathogens, and both increased in the resistome with repeated antibiotic use and/or increased duration. Conclusions: Given the strong association between opportunistic pathogens and multidrug-related efflux pumps, we suggest that drug efflux capacity might allow the opportunistic pathogens to persist or increase despite repeated courses and/or duration of antibiotics. While drug efflux is the most direct explanation, other mechanisms that enhance the ability of opportunistic pathogens to handle environmental stress, or other aspects of the treatment environment, could also contribute to their ability to flourish within the gut during treatment. Persistence of opportunistic pathogens in an already dysbiotic and weakened gastrointestinal tract could increase the likelihood of life-threatening blood borne infections. Of the 39 patients, 59% experienced at least one gastrointestinal or blood infection and 60% of bacteremia's were bacteria found in stool samples. Antimicrobial stewardship and appropriate use and duration of antibiotics could help reduce morbidity and mortality in this vulnerable population.

Survival effect of complete surgical resection of the primary tumor in patients with metastatic, high-risk neuroblastoma in a large Canadian cohort.

PURPOSE: To determine whether extent of surgical resection of the primary tumor correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. METHODS: Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001 and 2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumor based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem cell transplant (SCT). RESULTS: One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete versus incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p = .008 and p = .002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT, and surgical resection, only complete resection was associated with statistically significant improved 3 year EFS and OS, HR = 0.48 (0.29-0.81; p = .006) and HR = 0.42 (0.24-0.73; p = .002). CONCLUSIONS: In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.

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

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

Asparaginase activity monitoring and management of asparaginase hypersensitivity reactions in Canada.

INTRODUCTION: Pegaspargase can cause anti-asparaginase antibody formation, which can decrease its effectiveness without causing any clinically apparent reaction (silent inactivation). When a patient has silent inactivation, a switch to Erwinia anti-asparaginase is warranted, but there is currently a global shortage of Erwinia. The only way to identify silent inactivation is to measure an asparaginase level. However, routine asparaginase level monitoring is not currently standard of care at all Canadian centers. This study aims to identify variations in practice regarding asparaginase level monitoring and Erwinia use. METHODS: A 21-item survey was developed using OPINIO software and distributed to all Pediatric Hematology-Oncologists in Canada from February to October 2020. RESULTS: Respondents represented 15 hospitals across each region of Canada (response rate = 52%). Only 39.2% of respondents reported routinely measuring asparaginase levels, yet 53% of respondents have modified therapy from pegaspargase to Erwinia in up to half of their patients. The most common reason for not measuring asparaginase levels was not knowing how to use levels clinically (25.5%). There was variation in the timing of levels and their target. CONCLUSIONS: We identified substantial variation in asparaginase activity monitoring practices across Canada. Therefore, future research should aim to develop a national practice guideline on asparaginase activity monitoring.

Venous Thromboembolism Prophylaxis Use by Pediatric Orthopedic Surgeons in Canada for the Pediatric Orthopedic Surgical Population.

Introduction A novel pediatric venous thromboembolism (VTE) screening tool was implemented in 2016 at the Izaak Walton Killam (IWK) Health Centre, which safely reduced the use of thromboprophylaxis by 47.9% with no increase in VTE in the pediatric orthopedic surgical population (POSP). There is presently no data on the current practices or protocols for VTE prophylaxis for POSP in Canada. The present survey was designed to assess current practices regarding VTE prophylaxis for POSP in Canada. Methods After research ethics board (REB) approval, a 22-question survey was administered electronically to all Canadian Pediatric Orthopedic Group (CPOG) members. The survey contained questions on respondent demographics and background, current VTE prophylaxis practices and experiences including indications for prophylaxis, the existence of VTE protocols, and interest in utilizing VTE protocols. Descriptive statistical analyses and analysis of variance (ANOVA) were completed on the survey responses. Results Of the 100 CPOG members, 49 (49%) responded. Most respondents (51%, n=25/49) practice in Central Canada, 39% (n=19/49) practice in Western Canadian provinces, and a smaller portion practice in Atlantic Canada (10%, n=5/49). Of the respondents, 43% (n=21/49) indicated that they use pharmacologic VTE prophylaxis in their practice, and 93% (n=27/29) stated that specific risk factors are indications of initiating pharmacologic VTE prophylaxis. Additionally, 57% (n=16/28) did not have a defined protocol for VTE prophylaxis, and 18% (n=5/28) were uncertain if they do. Of the respondents, 85% (n=22/26) were open to utilizing a VTE prophylaxis screening tool, and 12% (n=3/26) were uncertain if they would be. Conclusion This study has demonstrated that a uniform protocol for VTE prophylaxis does not exist in most Canadian centers, despite its need. There is nationwide interest in adopting a perioperative VTE prophylaxis screening tool to optimize pharmacologic thromboprophylaxis use in POSP. The goal of future research is the national implementation and standardization of such a screening tool through collaboration in a multicenter study.

Prognostic factors and outcomes of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada: a report from CYP-C.

The epidemiology of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada is unknown. The main objective was to describe the prevalence, prognostic factors, and outcomes of three rare and high-risk ALL subtypes in Canada. This is a retrospective study using the Cancer in Young People-Canada (CYP-C) database. Event-free survival (EFS) and overall survival (OS) were described by the Kaplan-Meier method and compared using the log-rank test. Among 2626 children aged 0-14 years diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) between 2001 and 2018, 227 (8.6%) patients were identified to be infant ALL (n = 139), hypodiploid ALL (n = 43), or MPAL (n = 45). The 5-year EFS/OS was significantly worse in the infant ALL subgroup compared to that of hypodiploid ALL and MPAL. For the entire cohort, presenting White blood cells (WBCs) ≥50 × 109/L was independently associated with worse EFS/OS.

Antibiotic and antifungal use in pediatric leukemia and lymphoma patients are associated with increasing opportunistic pathogens and decreasing bacteria responsible for activities that enhance colonic defense.

Due to decreased immunity, both antibiotics and antifungals are regularly used in pediatric hematologic-cancer patients as a means to prevent severe infections and febrile neutropenia. The general effect of antibiotics on the human gut microbiome is profound, yielding decreased diversity and changes in community structure. However, the specific effect on pediatric oncology patients is not well-studied. The effect of antifungal use is even less understood, having been studied only in mouse models. Because the composition of the gut microbiome is associated with regulation of hematopoiesis, immune function and gastrointestinal integrity, changes within the patient gut can have implications for the clinical management of hematologic malignancies. The pediatric population is particularly challenging because the composition of the microbiome is age dependent, with some of the most pronounced changes occurring in the first three years of life. We investigated how antibiotic and antifungal use shapes the taxonomic composition of the stool microbiome in pediatric patients with leukemia and lymphoma, as inferred from both 16S rRNA and metagenome data. Associations with age, antibiotic use and antifungal use were investigated using multiple analysis methods. In addition, multivariable differential abundance was used to identify and assess specific taxa that were associated with multiple variables. Both antibiotics and antifungals were linked to a general decline in diversity in stool samples, which included a decrease in relative abundance in butyrate producers that play a critical role in host gut physiology (e.g., Faecalibacterium, Anaerostipes, Dorea, Blautia),. Furthermore, antifungal use was associated with a significant increase in relative abundance of opportunistic pathogens. Collectively, these findings have important implications for the treatment of leukemia and lymphoma patients. Butyrate is important for gastrointestinal integrity; it inhibits inflammation, reinforces colonic defense, mucosal immunity. and decreases oxidative stress. The routine use of broad-spectrum anti-infectives in pediatric oncology patients could simultaneously contribute to a decline in gastrointestinal integrity and colonic defense while promoting increases in opportunistic pathogens within the patient gut. Because the gut microbiome has been linked to both short-term clinical outcomes, and longer-lasting health effects, systematic characterization of the gut microbiome in pediatric patients during, and beyond, treatment is warranted.

Improving Financial Literacy Using the Medical Mini-MBA at a Canadian Medical School.

Introduction Financial literacy correlates with less debt and better retirement planning. Medical students, residents, and physicians often have poor financial literacy and large amounts of debt. We measured baseline financial literacy and whether it improved with the administration of a financial literacy course. Methods We created the Medical Mini-MBA,a six-week financial literacy course that targeted gaps in financial literacy among medical students and residents. Weekly topics included personal finance, investing, real estate and mortgage, physician billing and payment models, income and tax, and choosing a medical specialty. A 46-question financial literacy assessment was delivered to participants before and after the course. Results Of the 276 who participated in the course, 179 (64.86%) participated in the study. Participants who completed the course improved their financial literacy score by 10.10/46.00±5.12 (n=93, p<0.001). Self-assessment of financial literacy was positively correlated with financial literacy exam scores (r=0.366, p<0.001). Demographics such as gender, geography, education level, and first-degree relatives who are/were physicians had no effect on financial literacy scores. Conclusions The Medical Mini-MBA improved financial literacy at a Canadian medical school. Implementation of the coursemay equip medical students and residents for financial decisions. It avoids financial conflicts of interest and can supplement the medical curriculum.

Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth.

OBJECTIVE: To determine postdischarge iron status and associated factors in very preterm infants. STUDY DESIGN: A retrospective cohort study was conducted through a provincial database on all very preterm infants born in Nova Scotia between 2005 and 2018. As a standard of care, all infants received prophylactic iron supplements starting at 2-4 weeks of chronological age and were tested for iron deficiency at 4 or 6 months corrected age. Iron deficiency was defined as serum ferritin <20 g/L at 4 months or <12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency. RESULTS: Among 411 infants, 132 (32.1%) had iron deficiency and 11 (2.7%) had iron deficiency anemia. The prevalence of iron deficiency decreased over time, from 37.6% in 2005-2011 to 25.8% in 2012-2018. Gestational hypertension in the mother (P = .01) and gestational age <27 weeks (P = .02) were independent risk factors for iron deficiency. In addition, the odds of iron deficiency were lower in the mixed-fed group (ie, with breast milk and formula combined) compared with the exclusive formula-fed group (P = .01). CONCLUSIONS: Iron deficiency was prevalent in 32% of the very preterm infants despite early iron prophylaxis. These results demonstrate the importance of monitoring iron stores during preterm follow-up. Information about risk factors is important to mitigate iron deficiency in very preterm infants.

Recommendations for standardized definitions, clinical assessment, and future research in pediatric clinically unsuspected venous thromboembolism: Communication from the ISTH SSC subcommittee on pediatric and neonatal thrombosis and hemostasis.

Clinically unsuspected venous thromboembolism (VTE) in children is defined as a VTE diagnosed via imaging test performed for surveillance (i.e., with an intent to identify clinically silent VTEs) or incidentally found (most often via imaging performed for evaluation of regional pathology unrelated to VTE) in the absence of any VTE-associated signs or symptoms. Our understanding of the clinical significance of these events in children is limited by a paucity of data on the epidemiology and outcomes of this complication. There is an urgent need for further research in this area to inform optimal management. Recognizing this knowledge gap, this Task Force has previously published a systematic review of the literature in this topic. We now provide guidance recommendations for standardization of definitions and identify future research needs on clinically unsuspected VTE in children. These recommendations will serve to enhance the quantity and quality of evidence on the topic and facilitate the design and execution of cooperative observational studies, and interventional trials of risk-stratified management approaches aimed at preventing and optimizing long-term outcomes of clinically unsuspected VTE in children.

Challenges in Management of VTE in Children With Cancer: Risk Factors and Treatment Options.

Venous thromboembolism (VTE) occurs in 2.1 to up to 50% of children with cancer and contributes to long term morbidity as well as early mortality in this population. Pediatric patients with malignancy are predisposed to VTE due to the prothrombotic nature of cancer and its associated coagulopathies as well as chemotherapeutic agents, use of central venous catheters, surgery, radiotherapy, and concomitant thrombophilia. Management of thrombosis in this population is challenging due to concomitant thrombocytopenia, associated bleeding risks, concurrent co-morbidities, and toxicities of therapy. The aim of this paper is to highlight clinically relevant issues and management dilemmas using clinical vignettes. We review the clinical significance of asymptomatic and symptomatic thrombosis, examine the various options for asparaginase-associated thrombosis, address the role and controversies of direct oral anticoagulants, and describe our approach to managing anticoagulation therapy in the context of chemotherapy-induced thrombocytopenia.