Medulloblastoma and other neoplasms in patients with heterozygous germline SUFU variants: A scoping review.

In 2002, heterozygous suppressor of fused variants (SUFU+/-) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/- variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin-Goltz syndrome; OMIM 109400), an autosomal-dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/- variants is very poorly characterized due to a paucity of large studies with long-term follow-up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline SUFU+/- variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline SUFU+/- variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline SUFU+/- variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (N = 30 studies) identified with a confirmed germline SUFU+/- variant who met inclusion criteria. Data were extracted from two cohort studies, two case-control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline SUFU+/- variant was 4.5 years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline SUFU+/- variants, and the most common were medulloblastoma (N = 59 patients), BCC (N = 21 patients), and meningioma (N = 19 patients). The median age at medulloblastoma diagnosis was 1.42 years (range 0.083-3; interquartile range 1.2). When data were available for these three most frequent neoplasms (N = 95 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline SUFU+/- variant. This scoping review is a necessary step forward in optimizing evidence-based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes.

The "STOP Pain" Questionnaire: using the Plan-Do-Study-Act model to implement a patient-family preferences-informed questionnaire into a pediatric transitional pain clinic.

BACKGROUND: Patient engagement is an important tool for quality improvement (QI) and optimizing the uptake of research findings. The Plan-Do-Study-Act (PDSA) model is a QI tool that encourages ongoing evaluation of clinical care, thus improving various aspects of patient care. Ascertaining pediatric patient priorities for a pain questionnaire in the post-acute, or transitional pain, setting is important to guide clinical care since active engagement with the population of interest can optimize uptake. We used the PDSA model to adapt a chronic pain questionnaire for the pediatric transitional pain setting to reflect pediatric patient and parent/guardian preferences and to form an example of how the PDSA model can be used to improve clinical care through patient engagement. METHODS: This project employed the PDSA model to adapt the pediatric Ontario Chronic Pain Questionnaire for use in the pediatric Transitional Pain Service (pedTPS) setting. Plan: Following reviewing the Ontario Chronic Pain Questionnaire and literature on pain questionnaire development, goal-based questions, questions on pain location, relevant Patient-Reported Outcomes Measurement Information System (PROMIS®) measures and the Pain Catastrophizing Scale, child (PCS-C) and parent (PCS-P), informed the questionnaire. Do: The questionnaire and a satisfaction survey were sent to patients and families through Research Electronic Data Capture (REDCap™). STUDY: Results from the satisfaction survey were analyzed. Act: Using descriptive statistics employing ordinal mixed-models with random effects, ANOVA, and double-blinded qualitative thematic coding, questionnaire preferences were analyzed and the questionnaire was adapted accordingly before implementation into the (pedTPS). RESULTS: Eighty-eight questionnaires and satisfaction surveys were analyzed from 69 respondents (32 patients; 37 parents/guardians). Sixty-six (75.00%) surveys indicated satisfaction with the questionnaire. A combined 77 (87.50%) "strongly agreed" (25/88) or "agreed" (52/88) that the questionnaire language was clear. The application of suggested changes to the questionnaire resulted in four versions across the project timeline, which reflected patient and parent/guardian preferences for questions that reflect the themes, "Story"; "Time-Optimal"; and "Pertinent" ("STOP"). There were no statistically significant differences in satisfaction across the versions due to sample size. CONCLUSION: Most respondents were satisfied with the questionnaire and prefer "STOP" questions. Future studies will focus on testing the questionnaire for validity and reliability across pedTPS populations.

Patterns of joint damage in severe haemophilia A treated with prophylaxis.

OBJECTIVE: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first-year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership. METHODS: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort. We used a multinomial logistic regression to predict the odds of class membership based on the above predictors. We fitted a survival model to assess whether there were differences in the rate of dose escalation across the groups. RESULTS: We identified three distinct classes of trajectory: persistently low, moderately increasing and rapidly increasing joint scores. By multinomial regression, we found that only age at first index joint bleed predicted rapidly increasing joint scores. The rapidly increasing joint score class group moved through dose escalation significantly faster than the other two groups. CONCLUSIONS: Using tailored prophylaxis, boys with SHA follow one of three joint health trajectories. By using knowledge of disease trajectories, clinicians may be able to adjust treatment according to a subject's predicted long-term joint health and institute cost-effective programmes of prophylaxis targeted at the individual subject level.