Performance of bowel preparation quality scales in patients with Crohn's disease.

BACKGROUND: The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. AIMS: To evaluate the operating properties of instruments used to assess BP quality in patients with CD. METHODS: We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100-mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES-CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within-patient correlation between instruments and the visual analogue scale using mixed-effect models. The correlation between BP quality and SES-SD scores was assessed using Spearman's rho. RESULTS: Inter- and intra-rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter-rater reliability ICC ≥0.41). The visual analogue scale had substantial inter- and almost perfect (ICC ≥0.81) intra-rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. CONCLUSION: Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD.

Heated humidified high flow nasal cannula therapy in children with obstructive sleep apnea: A randomized cross-over trial.

OBJECTIVE/BACKGROUND: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in children with obesity and/or underlying medical complexity. The first line of therapy, adenotonsillectomy (AT), does not cure OSA in more than 50% of these children. Consequently, continuous positive airway pressure (CPAP) is the main therapeutic option but adherence is often poor. A potential alternative which may be associated with greater adherence is heated high-flow nasal cannula (HFNC) therapy; however, its efficacy in children with OSA has not been systematically investigated. The study aimed to compare the efficacy of HFNC with CPAP to treat moderate-to-severe OSA with the primary outcome measuring the change from baseline in the mean obstructive apnea/hypopnea index (OAHI). PARTICIPANTS/METHODS: This was a single-blinded randomized, two period crossover trial conducted from March 2019 to December 2021 at a Canadian pediatric quaternary care hospital. Children aged 2-18 years with obesity and medical complexity diagnosed with moderate-to-severe OSA via overnight polysomnography and recommended CPAP therapy were included in the study. Following diagnostic polysomnography, each participant completed two further sleep studies; a HFNC titration study and a CPAP titration study (9 received HFNC first, and 9 received CPAP first) in a random 1:1 allocation order. RESULTS: Eighteen participants with a mean ± SD age of 11.9 ± 3.8 years and OAHI 23.1 ± 21.7 events/hour completed the study. The mean [95% CI] reductions in OAHI (-19.8[-29.2, -10.5] vs. -18.8 [-28.2, -9.4] events/hour, p = 0.9), nadir oxygen saturation (7.1[2.2, 11.9] vs. 8.4[3.5, 13.2], p = 0.8), oxygen desaturation index (-11.6[-21.0, -2.3] vs. -16.0[-25.3, -6.6], p = 0.5) and sleep efficiency (3.5[-4.8, 11.8] vs. 9.2[0.9, 15.5], p = 0.2) with HFNC and CPAP therapy were comparable between conditions. CONCLUSION: HFNC and CPAP therapy yield similar reductions in polysomnography quantified measures of OSA severity among children with obesity and medical complexities. TRIAL REGISTRATION: NCT05354401 ClinicalTrials.gov.

Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

How essential are in-person clinic visits during maintenance treatment of children with acute lymphoblastic leukemia?

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Treatment consists of an initial intensive phase of chemotherapy, followed by a prolonged period of maintenance chemotherapy intended to reduce the risk of relapse. During the COVID-19 pandemic, the need arose to identify and reduce non-essential hospital visits. OBJECTIVE: We aimed to determine which proportion of in-person clinic visits during ALL maintenance therapy was associated with a change of management based on the results of the physical examination. PATIENTS AND METHODS: Medical records of children receiving maintenance chemotherapy for B-precursor ALL between September 2019 and February 2020 were reviewed. Visits with a new finding on physical examination were divided into those where an in-person assessment was deemed essential versus not essential. Finally, we determined the proportion of essential in-person visits that resulted in a change of management. RESULTS: A total of 240 maintenance visits by 75 children were analyzed. An abnormal finding on physical examination was noted during 20 visits (8.3%). Of those, 14 (5.8%) uncovered a new finding, six (2.5%) were classified as "in-person visit essential," and among those six visits, three (1.2%) resulted in a change of patient management (one for acute otitis media, one for wheezing, and one for limp). CONCLUSION: Our findings support the evaluation of care delivery models other than in-person visits during ALL maintenance therapy. A prospective study is required to delineate criteria, benefits/risks, and families' perspectives associated with virtual care delivery and the optimal frequency of in-person visits.

Determinants of access to childhood cancer medicines: a comparative, mixed-methods analysis of four Caribbean countries.

BACKGROUND: Equitable access to essential medicines is a key facet of childhood cancer care, recognised by WHO as vital to improved childhood cancer outcomes globally. In the Caribbean, childhood cancer outcomes are poorer than those in most high-income countries. We aimed to generate in-depth comparative evidence of the current challenges and opportunities related to access to childhood cancer medicines in the Caribbean to identify context-sensitive health systems strategies to improve drug access and inform evidence-based paediatric cancer policies in the region. METHODS: In this convergent, parallel, mixed-methods study, we mapped and analysed the determinants of access to childhood cancer medicines in four Caribbean countries (The Bahamas, Barbados, Jamaica, and Trinidad and Tobago). We analysed contextual determinants of access to medicines within and across study site jurisdictions, alignment of childhood cancer medicine inclusion between each country's national essential medicines list (NEML) and WHO's 2017 Essential Medicines List for Children, and availability and cost of chemotherapeutic agents at five tertiary care hospitals. We used a mixed-effects logistic regression model to analyse the association of medicine price, procurement efficiency (via median price ratio [MPR]), and site with drug availability. The fixed effect evaluated the effect of site and MPR on the probability of stockout in a given month. We assessed determinants of medicine access via thematic analysis of semi-structured qualitative interviews, literature, and policy documents. FINDINGS: We collected and analysed data for 28 childhood cancer medicines from Barbados, 32 from The Bahamas, 30 from Trinidad and Tobago, and 31 from Jamaica. Despite stepwise inclusion of childhood cancer medicines in NEMLs, all four countries had frequent and recurrent stockouts for many cytotoxic medicines, showing no consistent relationship between NEML inclusion and availability. A mean MPR of greater than 3·0 in Trinidad and Tobago, The Bahamas, and Barbados suggests uniformly high procurement inefficiency, resulting in significant effects on drug stockout days. For each one unit increase in MPR the adjusted odds ratio (OR) of stockout increased by 10% (adjusted OR 1·10, 95% CI 1·04-1·16; p<0·01). These challenges in access to childhood cancer medicines stem from health system and policy dynamics at institutional, national, and supranational levels that cause price volatility and erratic medicine availability. Key challenges include disparate policy commitments (eg, among sites), inefficient procurement and supply chain management practices, and local effects of international market pressures. INTERPRETATION: The Caribbean region exemplifies deficiencies in access to childhood cancer medicines that might be overcome by improved regional harmonisation of drug registration, pharmacovigilance, and procurement alongside national forecasting to strengthen global pharmaceutical planning and prioritisation. Focused political attention to address these challenges is required to ensure efficient, reliable, and sustained availability of cancer mediciness. FUNDING: The SickKids-Caribbean Initiative.

A Novel Instrument for Endoscopic Ear Surgery With a Steerable Flexible Tip: A Pediatric Anatomical Validation Study.

HYPOTHESIS: This study compares the reaching ability of two classes of transcanal endoscopic ear surgery (TEES) instruments when operating on difficult to access anatomical targets; two novel instruments with steerable flexible tips (SFT-A and SFT-B) and suction capability are compared with standard commercially available tools. BACKGROUND: TEES surgeons identified the need for a new surgical instrument that can enable accessibility of all areas visualized by the endoscope. This motivated the development of the two instrument prototypes. METHODS: Six temporal bone models were 3D printed based on CT data from five cholesteatoma patients. Four anatomical targets were marked on each model. Using these targets, the reaching ability while using four standard TEES instruments were compared with the SFT-A and SFT-B prototypes by five surgeon participants. Results were analysed to compare success rates of contacting each target using each tool by fitting four Firth's logistic regression models. This calculated the statistically significant differences (p < 0.05) in tool success rate. RESULTS: Using SFT-A to contact the sinus tympani (100%) was significantly more successful than the Panetti suction dissector for atticus (PAT) (77%) and to contact the sinodural angle (0%) was less successful than the PAT (10%) and SFT-B (93%). Using SFT-B to contact the lateral semicircular canal (90%) was significantly more successful than all current tools and to contact the sinodural angle (93%) was significantly more successful than all tools. CONCLUSION: Using SFT-B enables enhanced accessibility of anatomical structures during TEES which may lead to less extensive bone removal to facilitate minimally invasive TEES.

Causes of death in pediatric neuro-oncology: the sickkids experience from 2000 to 2017.

PURPOSE: Primary benign and malignant central nervous system (CNS) tumors are the most frequent solid tumors in the pediatric age and represent the leading cause of death by cancer in children in high income countries. However, information regarding specific causes of death in this population is still limited. The objective of this work was to investigate mortality in a large cohort of children diagnosed at our institution. METHODS: We identified patients consecutively diagnosed with CNS tumor and treated at a Tertiary Care Canadian Children's Hospital between January 2000 and December 2017. Patient charts were reviewed and different variables such as tumor diagnosis, location, gender, age at diagnosis, age at death and cause of death collected. RESULTS: Of 1274 patients, 306 (24%) succumbed to their disease. Mortality rate varied significantly according to tumor subtype, ranging from 3.1% in low grade glioma (LGG) to 97.8% in diffuse intrinsic pontine glioma (DIPG). While high grade gliomas (HGG) and DIPG represented only 6.3 and 7.1% of total diagnoses respectively, together they accounted for 49.3% of total deaths (n = 151). Median time from diagnosis to death was 15 months (4 days to 15 years) and shortest for DIPG (11 months). Two hundred and ninety patients (94.8%) died as a result of the primary disease, 4 of treatment-related toxicity, two patients' deaths were unrelated to the primary disease (idiopathic encephalopathy and domestic fire) whereas 10 patients succumbed to a secondary malignancy. Of note, four of these ten patients had a confirmed underlying cancer predisposition syndrome. CONCLUSION: Disease progression is the main cause of death in children with brain tumor, while treatment related mortality is low in this series. Research should continue to focus on improving treatment strategies for patients whose prognosis remains dismal.

Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence.

Seventeen children at six institutions with neurofibromatosis type 2 (NF2)-related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2-associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.

Comparison of logistic regression with machine learning methods for the prediction of fetal growth abnormalities: a retrospective cohort study.

BACKGROUND: While there is increasing interest in identifying pregnancies at risk for adverse outcome, existing prediction models have not adequately assessed population-based risks, and have been based on conventional regression methods. The objective of the current study was to identify predictors of fetal growth abnormalities using logistic regression and machine learning methods, and compare diagnostic properties in a population-based sample of infants. METHODS: Data for 30,705 singleton infants born between 2009 and 2014 to mothers resident in Nova Scotia, Canada was obtained from the Nova Scotia Atlee Perinatal Database. Primary outcomes were small (SGA) and large for gestational age (LGA). Maternal characteristics pre-pregnancy and at 26 weeks were studied as predictors. Logistic regression and select machine learning methods were used to build the models, stratified by parity. Area under the curve was used to compare the models; relative importance of predictors was compared qualitatively. RESULTS: 7.9% and 13.5% of infants were SGA and LGA, respectively; 48.6% of births were to primiparous women and 51.4% were to multiparous women. Prediction of SGA and LGA was poor to fair (area under the curve 60-75%) and improved with increasing parity and pregnancy information. Smoking, previous low birthweight infant, and gestational weight gain were important predictors for SGA; pre-pregnancy body mass index, gestational weight gain, and previous macrosomic infant were the strongest predictors for LGA. CONCLUSIONS: The machine learning methods used in this study did not offer any advantage over logistic regression in the prediction of fetal growth abnormalities. Prediction accuracy for SGA and LGA based on maternal information is poor for primiparous women and fair for multiparous women.

Pap tests in the diagnosis of cervical cancer: Help or hinder?

OBJECTIVE: To evaluate the impact of pap tests on the time to diagnosis of cervical cancer. METHODS: In this population-based retrospective cohort study, Ontario women ≥21 years diagnosed with cervical cancer between 2011 and 2014 were identified and database data collected. The presence or absence of a pap test 0-2 years preceding cancer diagnosis was identified. Descriptive and modelling analyses were performed to determine the effect of pap results on cancer diagnosis. RESULTS: 2002 patients were identified, 75% received a pap test. 1250 patients had known cytology - 13% normal, 8% low-grade and 7.5% suspicious for cancer. Across all FIGO stages at diagnosis, 5-10% of cytology was low grade, 3-11.5% was positive for carcinoma and 4-41% was normal, which increased with advancing stage. For all cytology and FIGO stages (except stage 1A), OBGYNs had a significantly shorter time to diagnosis compared to family physicians. Factors increasing the odds of low-grade cytology were advanced stage (OR 4.5 (2.4-8.0), p < 0.01) and adenocarcinoma (OR 1.5 (1.1-2.1), p < 0.01). Low grade cytology resulted in the longest delay to diagnosis (p < 0.001). CONCLUSION: Pap tests are performed frequently in the 0-2 years prior to the diagnosis of cervical cancer which can result in false negative cytology and diagnostic delay in patients with advanced cancers.

Seasonality in Pediatric Cancer.

Although seasonal trends in incidence and diagnosis of pediatric cancers have been widely investigated, the results have been inconclusive. A consistent seasonal trend may possibly provide etiological insights into pediatric cancers. This study aims to determine if there is a seasonal variation in cancer diagnoses in the pediatric population at the IWK Health Centre, a tertiary care center serving three Canadian provinces: Nova Scotia, New Brunswick, and Prince Edward Island. All pediatric cancer patients aged 0-20 y diagnosed from 1995 to 2015 at the center were included in this study. The annual data was divided into four seasonal periods (December to February, March to May, June to August, and September to November). The cancer diagnoses were categorized as leukemia, lymphoma, sarcoma, brain tumors, and miscellaneous. Seasonal variation was assessed by a harmonic function in a Poisson regression model. The amplitude of multiplicative change in the incidence rate caused by the seasonal variation is expressed as the incidence rate ratio (IRR). For all cancer diagnoses for the entire cohort of 1200 patients, the IRR was 1.03 [95% confidence interval (CI) 0.96-1.13]. None of the IRRs for the cancer groups indicated a statistically significant seasonality of cancer diagnosis: Leukemia 1.11 (95% CI 0.96-1.28); Lymphoma 1.17 (95% CI 0.93-1.47); Sarcoma 1.29 (95% CI 0.99-1.69); Brain tumors 1.16 (95% CI 0.97-1.38); Miscellaneous 1.09 (95% CI 0.93-1.27). The present study did not show a seasonal variation in the various cancer types in the pediatric population at the IWK.