Consensus reporting guidelines to address gaps in descriptions of ultra-rare genetic conditions.

Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains: (I) Development, cognition, and mental health; (II) Feeding and growth; (III) Medication use and treatment history; (IV) Pain, sleep, and quality of life; (V) Adulthood; and (VI) Epilepsy. For a subset of articles, all subsequent published follow-up case descriptions were identified and assessed in a similar manner. A modified Delphi approach was used to develop consensus reporting guidelines, with input from content experts across four countries. In total, 200 of 3243 screened publications met inclusion criteria. Relevant phenotypic details across each of the 6 domains were rated superficial or deficient in >87% of papers. For example, less than 10% of publications provided details regarding neuropsychiatric diagnoses and "behavioural issues", or about the type/nature of feeding problems. Follow-up reports (n = 95) rarely contributed this additional phenotype data. In summary, phenotype information relevant to clinical management, genetic counselling, and the stated priorities of patients and families is lacking for many newly described genetic diseases. The PHELIX (PHEnotype LIsting fiX) reporting guideline checklists were developed to improve phenotype reporting in the genomic era.

The Effect of Specialized Palliative Care on End-of-Life Care Intensity in AYAs with Cancer.

CONTEXT: Many adolescents and young adults (AYAs; 15-39 years) with cancer receive high intensity (HI) care at the end of life (EOL). Palliative care (PC) involvement in this population is associated with lower risk of HI-EOL care. Whether this association differs by specialized vs. generalist PC (SPC, GPC) is unknown. OBJECTIVES: (1) To evaluate whether SPC had an impact on the intensity of EOL care received by AYAs with cancer; (2) to determine which subpopulations are at highest risk for reduced access to SPC. METHODS: A decedent cohort of AYAs with cancer who died between 2000-2017 in Ontario, Canada was identified using registry and population-based data. The primary composite measure of HI-EOL care included any of: intravenous chemotherapy <14 days from death; more than one ED visit, more than one hospitalization or any ICU admission <30 days from death. Physician's billing codes were used to define SPC and GPC involvement. RESULTS: Of 7122 AYA decedents, 2140 (30%) received SPC and 943 (13%) received GPC. AYAs who died in earlier years, those with hematologic malignancies, males and rural AYAs were least likely to receive SPC. No PC involvement was associated with higher odds of receiving HI-EOL care (odds ratio (OR) 1.5; P < 0.0001). SPC involvement was associated with the lowest risk of HI-EOL care (OR SPC vs. GPC 0.8; P = 0.007) and decreased odds of ICU admission (OR 0.7; P = 0.006). CONCLUSION: SPC involvement was associated with the lowest risk of HI-EOL care in AYAs with cancer. However, access to SPC remains a challenge.

Pediatric and Adult Cardiologists' and Respirologists' Referral Practices to Palliative Care.

CONTEXT: Children and adults with advanced cardiac or respiratory disease may benefit from specialized palliative care (SPC), but there has been little SPC research in this area. OBJECTIVES: To explore pediatric cardiologists' and respirologists' (pediatric clinicians) beliefs about and referral practices to SPC and compare these results to adult cardiologists and respirologists (adult clinicians). METHODS: Pediatric and adult clinicians were sent a survey exploring SPC referral practices and beliefs. Responses were summarized with descriptive statistics. Pediatric and adult clinicians' responses were compared using Pearson's chi-square test. RESULTS: The response rate was 56% (989/1759); 9% (87/989) were pediatric clinicians. Pediatric clinicians were more likely than adult clinicians to be female, work in an academic center, and experience fewer patient deaths (P<0.001). Pediatric clinicians reported better access to SPC clinical nurse specialists, spiritual care specialists and bereavement counselors (P<0.001), while adult clinicians reported better access to palliative care units (P<0.001). Pediatric clinicians referred to SPC earlier, while adult clinicians tended to refer after disease directed therapies were stopped (P<0.001). More than half of all clinicians felt patients had negative perceptions of the phrase "palliative care". Although most clinicians were satisfied with SPC quality (73-82%), fewer adult clinicians were satisfied with SPC availability (74 vs. 47%; P<0.001). Fewer pediatric clinicians felt that SPC prioritized oncology patients (13 vs. 53%; P<0.001). CONCLUSION: There are important differences between pediatric and adult clinicians' beliefs about and referral practices to SPC. This may reflect unique features of pediatric diseases, provider characteristics, care philosophies, or service availability.

The impact of polysomnograms and family-centred decision making in children with medical complexity.

Objectives: To determine whether a change in clinical management (e.g., new tracheostomy or adenotonsillectomy) occurred following a polysomnogram (PSG) in children with medical complexity (CMC) and to explore whether families' goals of care (regarding results and treatment implications) were discussed prior to the completion of a PSG. Methods: All CMC enrolled in a complex care program at the Hospital for Sick Children, Canada, who underwent a baseline PSG from 2009 to 2015 were identified. Exclusion criteria included (1) PSGs for ventilation titration and (2) PSGs outside the study time frame. Health records were retrospectively reviewed to determine demographics, medical histories, families' wishes, PSG results, and their impact on clinical care. Descriptive statistics were used to summarize results. Results: Of 145 patients identified, 96 patients met inclusion criteria. Fifty (52%) were male. Median age was 3 years. Forty-eight (50%) were diagnosed with clinically significant (i.e., moderate to severe obstructive sleep apnea, central sleep apnea, and/or hypoventilation) sleep-related breathing disorders. Of those diagnosed, 9 (19%) had surgery, 25 (52%) underwent respiratory technology initiation, and 3 (6%) underwent both. In the remaining 11 (23%) patients, treatment was either considered too risky or did not align with the families' wishes. Only 3 of 96 patients had clear documentation of their families' wishes prior to PSG completion. Conclusion: Recognizing the burden of medical tests for both the child and the health care system, a process of shared-decision making that includes clarifying a family's wishes may be prudent prior to conducting a PSG.

Illness intrusiveness and subjective well-being in patients with glioblastoma.

Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlling for disease and treatment variables. In this cross-sectional cohort study, we examined the relations among illness intrusiveness, disease burden, and subjective well-being in GBM. 73 GBM patients completed validated self-report measures of depression, positive affect, illness intrusiveness, and health-related QOL. Responses were compared to data from six other cancer groups using repeated measures analyses of variance. Hierarchical multiple-regression analyses tested the hypothesis that illness intrusiveness accounts for well-being after controlling for the effects of disease burden. GBM patients reported less positive affect, more depression, and more illness intrusiveness than people with other cancers. Illness intrusiveness correlated with depression and (low) positive affect. Associations among cancer symptoms, depression, and positive affect decreased when illness intrusiveness was added to regression equations. Good performance status and high cancer-symptom burden were associated with illness intrusiveness and depression. GBM patients report greater distress, lower positive affect, and more illness intrusiveness than people with other cancers. Subjective well-being is mediated in part by illness intrusiveness in this population. In addition to medical treatment, efforts to help patients remain engaged in valued activities and interests may help preserve QOL after the diagnosis of a GBM.

Development and Evaluation of Patient Education Materials for Elderly Lung Cancer Patients.

Patients treated for lung cancer are often elderly presenting a unique challenge for developing patient education materials. This study developed and evaluated a patient education pamphlet on lung stereotactic body radiotherapy (SBRT) designed specifically for an elderly population. The SBRT pamphlet was developed using a participatory design involving a convenience sample of patients. This prospective study assessed patient's opinions of pamphlet effectiveness through self-report questionnaires. The pamphlet was deemed "effective" if patients rated 16/18 evaluation statements as "strongly agree" or "agree." Demographic data and health literacy (Rapid Estimate of Adult Literacy in Medicine short-form (REALM-SF)) were also assessed. Patient opinion of pamphlet "effectiveness" was compared between patients with REALM-SF scores of 7 versus <7 using Fisher's exact test. The overall EQ-5D-5L score was compared for patients who did and did not find the pamphlet effective using the Wilcoxon-Mann-Whitney test. Thirty-seven patients participated. The median age was 76 years (range 56-93) and 22 patients (59 %) had ≤high school education. Most patients preferred to have verbal (65 %) or written (78 %) educational materials as opposed to online information or educational classes. Thirty-two patients (86 %) rated the pamphlet as effective. The proportion of patients who found the pamphlet effective was 85.7 versus 86.7 % (p = 1.00) in those with REALM 7 versus <7. The mean EQ-5D score was 67.5 (SD 19.1) versus 71.8 (SD 8.7) (p = 0.84) in those who found the pamphlet effective versus not. Participatory design is an effective method for developing education materials for challenging patient groups such as elderly patients. Despite advanced age and comorbidity, this patient group had adequate health literacy.

Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes.

Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.