Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis.

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.

Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes.

BACKGROUND: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation. METHODS: This study assessed MIPOGG's performance in identifying Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin (nevoid basal cell carcinoma) syndromes in a retrospective series of 84 children diagnosed with cancer and one of these four CPSs in Canadian hospitals over an 18-year period. RESULTS: MIPOGG detected 82 of 83 (98.8%) evaluable patients with any one of these four genetic conditions and demonstrated an appropriate rationale for suggesting CPS evaluation. When compared with syndrome-specific clinical screening criteria, MIPOGG's ability to correctly identify children with any of the four CPSs was equivalent to, or outperformed, existing clinical criteria respective to each CPS. CONCLUSION: This study adds evidence that MIPOGG is an appropriate tool for CPS screening in clinical practice. MIPOGG's strength is that it starts with a specific cancer diagnosis and incorporates criteria relevant for associated CPSs, making MIPOGG a more universally accessible diagnostic adjunct that does not require in-depth knowledge of each CPS.

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.

Estimating the impact of menstrual poverty on adolescents in Nova Scotia.

Background: Menstrual poverty is defined as the inability of people who menstruate to obtain menstrual products due to financial burden. The impact of menstrual poverty is not well studied in developed countries. Objectives: This study aims to estimate the impact of menstrual poverty on adolescents who reside in Nova Scotia (NS), Canada. Methods: A web-based, 25-item questionnaire, the adolescent Menstrual Poverty Questionnaire (aMPQ), was developed and distributed via social media. Adolescents less than 18 years of age, English-speaking and living in NS were eligible to complete the questionnaire. Data were analysed using descriptive analysis. Results: Four hundred and twenty adolescents completed the questionnaire, with a mean age of 16.1 years (14.4-17.9 years). Results revealed that 65% of respondents do not always have enough money to buy menstrual products. This led to unsafe menstrual hygiene practices including using alternatives for menstrual products (e.g., rags), washing disposable menstrual products, and/or wearing products for longer than intended. Forty percent of respondents reported lack of affordability of menstrual products as a cause for school absenteeism and lack of participation in sport/social activities. Seventy percent of respondents felt embarrassed to ask for products even when they are provided for free, and almost all supported the idea of having freely available menstrual products in public washrooms. Conclusions: This study determined that menstrual poverty impacts adolescents in Nova Scotia. To address menstrual poverty, menstrual products should be freely available in all public washrooms, as this will provide unrestricted access to menstruators and promote their full participation in society.

Quality of life in adolescents with heavy menstrual bleeding: Validation of the Adolescent Menstrual Bleeding Questionnaire (aMBQ).

BACKGROUND/OBJECTIVES: Heavy menstrual bleeding (HMB) affects 34% to 37% of adolescent girls. The Menstrual Bleeding Questionnaire (MBQ) is a validated measure of menstrual bleeding-specific health-related quality of life (HRQoL) for women aged ≥18 years. No similar measure existed for adolescents with HMB. PATIENTS/METHODS: HMB was defined by the Pictorial Bleeding Assessment Chart (PBAC) score ≥100. In Phase 1, a focus group of adolescents with HMB adapted the MBQ, to generate the Adolescent MBQ (aMBQ). In phase 2, participants with and without HMB were recruited from clinics and self-referral. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life module [PedsQL]©, PBAC) at two time points. Validity of the aMBQ was assessed by Pearson's correlation with the PedsQL©. Reliability was calculated using intra-class correlation (ICC) in those without HMB. The receiver operating characteristic curve assessed the aMBQ's ability to identify those with HMB. RESULTS: Phase 1 included five girls with a mean age of 17.1 (13-18) years. The aMBQ was adapted from the MBQ by substituting four words/phrases that altered 8 of the 20 questions and by adding 1 new question. The 21-item aMBQ has a score range of 0 to 77 (77 = worst HRQoL). Phase 2 included 52 participants: 20 with and 32 without HMB, with a mean age of 14.8 (11-17) years. The validity of the aMBQ was confirmed by a moderate correlation with PedsQL© (r = -0.63; P < .001). Test-retest reliability was substantial (ICC = 0.73; P = .04). An aMBQ score of >30 identified those with HMB with excellent discrimination (area under the curve = 0.82; sensitivity, 70.0%; specificity, 84.4%). CONCLUSIONS: The aMBQ is a valid and reliable tool to assess HRQoL in adolescents with HMB.

Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes.

IMPORTANCE: Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading to missed CPS diagnoses. Advances in electronic health technology can facilitate CPS risk assessment. OBJECTIVE: To evaluate the diagnostic accuracy of a CPS prediction tool (McGill Interactive Pediatric OncoGenetic Guidelines [MIPOGG]) in identifying children with cancer who have a low or high likelihood of having a CPS. DESIGN, SETTING, AND PARTICIPANTS: In this international, multicenter diagnostic accuracy study, 1071 pediatric (<19 years of age) oncology patients who had a confirmed CPS (12 oncology referral centers) or who underwent germline DNA sequencing through precision medicine programs (6 centers) from January 1, 2000, to July 31, 2020, were studied. EXPOSURES: Exposures were MIPOGG application in patients with cancer and a confirmed CPS (diagnosed through routine clinical care; n = 413) in phase 1 and MIPOGG application in patients with cancer who underwent germline DNA sequencing (n = 658) in phase 2. Study phases did not overlap. Data analysts were blinded to genetic test results. MAIN OUTCOMES AND MEASURES: The performance of MIPOGG in CPS recognition was compared with that of routine clinical care, including identifying a CPS earlier than practitioners. The tool's test characteristics were calculated using next-generation germline DNA sequencing as the comparator. RESULTS: In phase 1, a total of 413 patients with cancer (median age, 3.0 years; range, 0-18 years) and a confirmed CPS were identified. MIPOGG correctly recognized 410 of 412 patients (99.5%) as requiring referral for CPS evaluation at the time of primary cancer diagnosis. Nine patients diagnosed with a CPS by a practitioner after their second malignant tumor were detected by MIPOGG using information available at the time of the first cancer. In phase 2, of 658 children with cancer (median age, 6.6 years; range, 0-18.8 years) who underwent comprehensive germline DNA sequencing, 636 had sufficient information for MIPOGG application. When compared with germline DNA sequencing for CPS detection, the MIPOGG test characteristics for pediatric-onset CPSs were as follows: sensitivity, 90.7%; specificity, 60.5%; positive predictive value, 17.6%; and negative predictive value, 98.6%. Tumor DNA sequencing data confirmed the MIPOGG recommendation for CPS evaluation in 20 of 22 patients with established cancer-CPS associations. CONCLUSIONS AND RELEVANCE: In this diagnostic study, MIPOGG exhibited a favorable accuracy profile for CPS screening and reduced time to CPS recognition. These findings suggest that MIPOGG implementation could standardize and rationalize recommendations for CPS evaluation in children with cancer.

Observational Study of Qigong as a Complementary Self-Care Practice at a Tertiary-Care Pain Management Unit.

Qigong, which can be characterized in many different ways, is offered as a complementary self-care practice at a tertiary-care pain management unit in Halifax, Nova Scotia. This report provides a quantitative and qualitative assessment of two groups engaged in qigong practice in this context as part of two Research in Medicine (RIM) projects (2014-15, 2016-17). It includes assessments of pain, mood, quality of life, sleep, and fatigue, considers outcomes in relation to the amount of practice, and considers whether health attitudes would help determine who might benefit from the practice. There were 43 participants (28 ongoing practitioners, 15 new to qigong). The ongoing practice group in RIM2 had significant benefits over time in pain, mood, quality of life, and fatigue in quantitative scores, but changes were not significant in RIM 1. There were no differences in any measures in those new to qigong. Qualitative comments in core and other domains reflected good or better outcomes in 16 subjects in the ongoing group who practiced consistently. In those who practiced less, results were more variable. In most of those new to qigong, the practice was limited and comments indicate minimal changes. Those engaged in qigong have a stronger internal health locus of control than control subjects. Diligent qigong practice provides multiple health benefits for those with chronic pain, and qualitative assessments are essential for documenting these effects. For those new to qigong, factors needed to effectively engage practice need to be explored further to optimize program delivery. The trial is registered with http://www.clinicaltrials.gov (NCT04279639).

Short-Term Test-Retest Reliability of Electrically Evoked Cortical Auditory Potentials in Adult Cochlear Implant Recipients.

Background: Late latency auditory evoked potentials (LLAEPs) provide objective evidence of an individual's central auditory processing abilities. Electrically evoked cortical auditory evoked potentials (eCAEPs) are a type of LLAEP that provides an objective measure of aided speech perception and auditory processing abilities in cochlear implant (CI) recipients. Aim: To determine the short-term test-retest reliability of eCAEPs in adult CI recipients. Design: An explorative, within-subject repeated measures research design was employed. Study Sample: The study sample included 12 post-lingually deafened, unilaterally implanted adult CI recipients with at least 9 months of CI experience. Method: eCAEPs representing basal, medial and apical cochlear regions were recorded in the implanted ears of each participant. Measurements were repeated 7 days after the initial assessment. Results: No significant differences between either median latencies or amplitudes at test and retest sessions (p > 0.05) were found when results for apical, medial and basal electrodes were averaged together. Mean intraclass correlation coefficient (ICC) scores averaged across basal, medial and apical cochlear stimulus regions indicated that both consistency and agreement were statistically significant and ranged from moderate to good (ICC = 0.58-0.86, p < 0.05). ICC confidence intervals did demonstrate considerable individual variability in both latency and amplitudes. Conclusion: eCAEP latencies and amplitudes demonstrated moderate to good short-term test-retest reliability. However, confidence intervals indicated individual variability in measurement consistency which is likely linked to attention and listening effort required from the CI recipients.