School Attendance Among Pediatric Oncology Patients During the COVID-19 Pandemic in Ontario, Canada.

Supporting schooling for current and past pediatric oncology patients is vital to their quality of life and psychosocial recovery. However, no study has examined the perspectives toward in-person schooling among pediatric oncology families during the COVID-19 pandemic. In this online survey study, we determined the rate of and attitudes toward in-person school attendance among current and past pediatric oncology patients living in Ontario, Canada during the 2020-2021 school year. Of our 31-family cohort, 23 children (74%) did attend and 8 (26%) did not attend any in-person school during this time. Fewer children within 2 years of treatment completion attended in-person school (5/8; 62%) than those more than 2 years from treatment completion (13/15; 87%). Notably, 22 of 29 parents (76%) felt that speaking to their care team had the greatest impact compared to other potential information sources when deciding about school participation, yet 13 (45%) were unaware of their physician's specific recommendation regarding whether their child should attend. This study highlights the range in parental comfort regarding permitting in-person schooling during the COVID-19 pandemic. Pediatric oncologists should continue to address parental concerns around in-person school during times of high transmission of COVID-19 and potentially other communicable diseases in the future.

Rates and predictors of visits to primary care physicians during and after treatment of childhood acute lymphoblastic leukemia: A population-based cohort study.

INTRODUCTION: Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL). METHODS: Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables. RESULTS: A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p < .0001). CONCLUSIONS: Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment.

The Impact of ABAWD Time Limit Reinstatement on SNAP Participation and Employment.

OBJECTIVE: Estimate the impact of the Supplemental Nutrition Assistance Program (SNAP) time limit for able-bodied adults without dependents (ABAWD) on SNAP participation, employment, and earnings. DESIGN: A quasi-experimental study using state administrative SNAP and earnings data to compare outcomes for SNAP participants before and after the time limit went into effect. PARTICIPANTS: Supplemental Nutrition Assistance Program participants in the study cohorts in Colorado, Missouri, and Pennsylvania (N = 153,599). MAIN OUTCOME MEASURES: Monthly SNAP participation, quarterly employment, annual earnings. ANALYSIS: Logistic and ordinary least squares multivariate regression models. RESULTS: Time limit reinstatement reduced SNAP participation by 7 to 32 percentage points in the 12th month of time limit reinstatement but did not generate evidence of improved employment or annual earnings (1 year after time limit reinstatement, employment decreased by 2 to 7 percentage points and annual earnings decreased by $247 to $1,230). CONCLUSIONS AND IMPLICATIONS: The ABAWD time limit reduced SNAP participation but did not improve employment and earnings. SNAP may provide helpful support to participants as they seek to enter or re-enter employment, and removing this support may be detrimental to their employment prospects. These findings can inform decisions about requesting waivers or pursuing changes to ABAWD legislation or regulations.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Healthcare utilization and costs associated with acute lymphoblastic leukemia in children with and without Down syndrome.

BACKGROUND: Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies. METHODS: A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates. RESULTS: Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p < .002). CONCLUSIONS: Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies.

Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors.

PURPOSE: Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS. METHODS: Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development. RESULTS: Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation. CONCLUSION: MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.

End-of-Life Childhood Cancer Research: A Systematic Review.

CONTEXT: Children with incurable cancer may participate in research studies at the end of life (EOL). These studies create knowledge that can improve the care of future patients. OBJECTIVE: To describe stakeholder perspectives regarding research studies involving children with cancer at the EOL by conduct of a systematic review. DATA SOURCES: We used the following data sources: Ovid Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, and ProQuest (inception until August 2020). STUDY SELECTION: We selected 24 articles published in English that examined perceptions or experiences of research participation for children with cancer at the EOL from the perspectives of children, parents, and health professionals (HPs). DATA EXTRACTION: Two authors independently extracted data, assessed study quality, and performed thematic analysis and synthesis. RESULTS: Eight themes were identified: (1) seeking control; (2) faith, hope, and uncertainty; (3) being a good parent; (4) helping others; (5) barriers and facilitators; (6) information and understanding; (7) the role of HPs in consent and beyond; and (8) involvement of the child in decision-making. LIMITATIONS: Study designs were heterogeneous. Only one study discussed palliative care research. CONCLUSIONS: Some families participate in EOL research seeking to gain control and sustain hope, despite uncertainty. Other families choose against research, prioritizing quality of life. Parents may perceive research participation as the role of a "good parent" and hope to help others. HPs have positive views of EOL research but fear that parents lack understanding of the purpose of studies and the likelihood of benefit. We identified barriers to research participation and informed consent.

Pregnancy Screening and Contraceptive Counseling in Young Women with Hodgkin Lymphoma: A Single Center Retrospective Review.

Purpose: Chemotherapeutic agents used to treat Hodgkin lymphoma are teratogenic. Pregnancy screening before the start of chemotherapy is supported by clinical guidelines. There are limited data on pregnancy screening before the start of Hodgkin therapy but previous studies suggest that it is not consistently completed. The objective of this study is to evaluate the completion of pregnancy screening before the start of chemotherapy in females with Hodgkin lymphoma. Methods: A retrospective chart review was performed for all female patients, regardless of age, with newly diagnosed Hodgkin lymphoma from 2000 to 2015 at the Hospital for Sick Children. Demographic, disease, and treatment data were captured. Outcome data included completion of pregnancy testing within 2 weeks before the start of therapy and documentation of contraceptive counseling. Results: One hundred twenty-two female patients with Hodgkin lymphoma between the ages of 5 and 17 years were identified. Sixty patients (49%) had ß-human chorionic gonadotropin (ß-HCG) testing done before the start of therapy. Testing modalities included serum and urine qualitative and serum quantitative ß-HCG tests. Older age (p < 0.01), documentation of menstrual status (p = 0.02), and diagnosis between 2008 and 2015 (p < 0.01) were associated with higher incidence of screening, although enrollment on a therapeutic trial was not (p = 0.37). Contraceptive counseling was documented for 19 patients (16%), and 11 patients (9%) were prescribed contraceptive medications. Conclusion: Prechemotherapy pregnancy screening was completed on less than half of females with Hodgkin lymphoma. The adoption of strategies to improve the consistency of pregnancy screening is required.

The minimally important difference for patient-reported outcomes in spondyloarthropathies including pain, fatigue, sleep, and Health Assessment Questionnaire.

OBJECTIVE: To study minimal important differences (MID) in spondyloarthropathies (SpA). MID are important in determining clinically relevant changes and for interpretation of trials and treating patients. MID have been widely studied in rheumatoid arthritis, but less so in SpA. METHODS: Patients with SpA had to be seen for 2 consecutive visits and have completed the Health Assessment Questionnaire (HAQ) and 100 mm visual analog scale on both visits for fatigue, pain, sleep, and global assessment. At the second visit they had to answer a question regarding any change in their overall health (from last visit), responding with much better, better, same, worse, or much worse. The MID were the mean changes for those who were either better or worse. RESULTS: Our study involved 140 eligible patients with a SpA: 69% were men, the mean age was 45 years, and the mean disease duration was 14.5 years. Almost half the patients rated themselves as unchanged from the previous visit but the remainder were either better or worse, with a minority rating themselves as much better or much worse. The MID for better and worse outcomes were HAQ (-0.136; 0.220), pain (-6.93; 18.97), fatigue (-1.43; 14.42), and sleep (-2.23; 10.76). No gender differences were observed. CONCLUSION: Our results demonstrate that the MID vary depending on better versus worse (bidirectionally different). MID may be smaller in clinical practice than what is observed in trials.

Effect of ring size on conformation and biological activity of cyclic cationic antimicrobial peptides.

In a series of cyclic peptides based on GS10, an analogue of gramicidin S (GS), the ring size was varied from 10 to 16 amino acids. Alternative addition of basic and hydrophobic amino acids to the original GS10 construct generated a variety of even-numbered rings, i.e., GS10 [cyclo-(VKLdYPVKLdYP)], GS12 [cyclo-(VKLKdYPKVKLdYP)], GS14 [cyclo-(VKLKVdYPLKVKLdYP), and GS16 [cyclo-(VKLKVKdYPKLKVKLdYP)] (d stands for d-enantiomers). The odd-numbered analogues (11-, 13-, and 15-mers) were derived from these four peptides by either addition or deletion of single basic (Lys) or hydrophobic (Leu or Val) amino acids. The resulting peptides, divided into three groups on the basis of peptide ring size (10- to 12-meric, 13- and 14-meric, and 15- and 16-meric), illustrated a diverse spectrum of biological activity correlated to their ring size, degree of beta-structure disruption, charge, hydrophobicity, amphipathicity, and affinity for lipid membranes. Two of these peptides with potent antimicrobial activities and high therapeutic indexes (4.5- to 10-fold compared with GS) are promising candidates for development of broad-spectrum antibiotics.

Interaction of gramicidin S and its aromatic amino-acid analog with phospholipid membranes.

To investigate the mechanism of interaction of gramicidin S-like antimicrobial peptides with biological membranes, a series of five decameric cyclic cationic beta-sheet-beta-turn peptides with all possible combinations of aromatic D-amino acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar identical with Phe, Tyr, Trp), were synthesized. Conformations of these cyclic peptides were comparable in aqueous solutions and lipid vesicles. Isothermal titration calorimetry measurements revealed entropy-driven binding of cyclic peptides to POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems was endothermic-exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs with exothermic binding to POPC vesicles. Application of one- and two-site binding (partitioning) models to binding isotherms of exothermic and endothermic binding processes, respectively, resulted in determination of peptide-lipid membrane binding constants (K(b)). The K(b1) and K(b2) values for endothermic two-step binding processes corresponded to high and low binding affinities (K(b1) >or= 100 K(b2)). Conformational change of cyclic peptides in transferring from buffer to lipid bilayer surfaces was estimated using fluorescence resonance energy transfer between the Tyr-Trp pair in one of the peptide constructs. The cyclic peptide conformation expands upon adsorption on lipid bilayer surface and interacts more deeply with the outer monolayer causing bilayer deformation, which may lead to formation of nonspecific transient peptide-lipid porelike zones causing membrane lysis.

Tax subsidies for private health insurance.

The exclusion from income and payroll taxes for employer-paid health insurance premiums amounted to more than $240 billion in 2010. As policy-makers search for ways to pay for health care reform and contain health care costs, this exclusion is coming under scrutiny, despite the fact that employee-sponsored insurance (ESI) is an integral part of the health insurance system. This update of a 2003 synthesis looks at the tax subsidy for private health insurance. Key findings include: The current tax subsidy benefits higher-income workers the most. The tax exclusion is worth more to those in higher tax brackets, higher-income workers are three times more likely to work for firms who offer ESI than lower-income workers, and they are more likely to purchase ESI when offered because they can afford it. Families earning $10,000 to $20,000 annually spend more than 25 percent of their income on health insurance but the value of their tax subsidy is only $1,500. By contrast, earners over $200,000 spend less than 5 percent on health insurance but their benefit is worth $4,500. Workers who cannot afford ESI or are ineligible, including the self-employed and many part-time workers, do not receive this subsidy when they purchase private, non-group coverage.