Children's and adolescents' perspectives on living with advanced cancer: A meta-synthesis of qualitative research.

PURPOSE: The quality of life (QOL) experiences of children and adolescents living with advanced cancer have been under-explored. Enhancing QOL for this population is a dominant goal of their healthcare yet, there has been little research identifying aspects that impact their QOL. The purpose of this meta-synthesis was to identify themes of QOL informed from the voices of children and adolescents living with advanced cancer. METHODS: This meta-synthesis utilized meta-ethnography to synthesize data from individual studies in order to develop new conceptual understanding of what is important to children and adolescents about their lives when living with advanced cancer. RESULTS: Our analysis identified themes of QOL relevant to children and adolescents with advanced cancer: (1) feeling supported and wanting to support others; (2) re-establishing normal; (3) suffering and emotional distress; (4) new perspectives; (5) maintaining autonomy; and (6) awareness of time. These themes differed from more traditional dimensions of QOL often applied to children and adolescents with cancer. CONCLUSION: This research is novel as its developed themes originated from the direct voices and expressed perspectives of children and adolescents living with advanced cancer. This is a significant initial step toward both understanding QOL in this specific context and the measurement of QOL for this population.

How children and adolescents understand the quality of their lives while living with advanced cancer that is difficult to cure is largely unknown and has not been extensively studied. A significant number of children and adolescents will live with advanced cancer however, it is not well-understood how children and adolescents define their quality of life (QOL) and which aspects of their lives feel meaningful to them while living with advanced cancer. This is important as their understanding and perspectives of their QOL might be very different from what their parents and healthcare professionals caring for them might identify as meaningful to their QOL. This research used the voices of children and adolescents with advanced cancer that were included in diverse research studies examining children and adolescents' experiences living with advanced cancer to develop themes of QOL for this group of young people. It was important to focus on their voices as we wanted to know directly from children and adolescents living with advanced cancer what feels meaningful and relevant to their lives. Our research identified aspects of QOL important to children and adolescents with advanced cancer that are different from how QOL is traditionally understood for children and adolescents with cancer. These findings can contribute to enhancing the healthcare of children and adolescents living with advanced cancer by suggesting that children and adolescents with advanced cancer have distinct QOL experiences and needs.

Patient Factors Associated with Missed Otolaryngology Appointments at an Urban Safety-Net Hospital.

OBJECTIVE: To determine if patient factors related to ethnicity, socioeconomic status (SES), medical comorbidities, or appointment characteristics increase the risk of missing an initial adult otolaryngology appointment. METHODS: This study is a retrospective case control study at Boston Medical Center (BMC) in Boston, Massachusetts, that took place in 2019. Patient demographic and medical comorbidity data as well as appointment characteristic data were collected and compared between those that attended their initial otolaryngology appointment versus those who missed their initial appointment. Chi-square and ANOVA tests were used to calculate differences between attendance outcomes. Multivariate analysis was used to compare the odds of missing an appointment based on various patient- and appointment-related factors. RESULTS: Patients who were more likely to miss their appointments were more often female, of lower education, disabled, not employed, Black or Hispanic, and Spanish-speaking. Spring and Fall appointments were more likely to be missed. When a multivariate regression was conducted to control for social determinants of health (SDOH) such as race, insurance status, employment, and education status, the odds of females, Spanish-speaking, students, and disabled patients missing their appointment were no longer statistically significant. CONCLUSION: A majority of patients at BMC come from lower SES backgrounds and have multiple medical comorbidities. Those who reside closer to BMC, often areas of lower average income, had higher rates of missed appointments. Interventions such as decreasing lag time, providing handicap-accessible free transportation, and increasing accessibility of telemedicine for patients could help improve attendance rates at BMC. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Use of Infrared Thermography in Medical Diagnosis, Screening, and Disease Monitoring: A Scoping Review.

Thermography provides non-invasive, radiation-free diagnostic imaging. Despite the extensive literature on medical thermography, a comprehensive overview of current applications is lacking. Hence, the aim of this scoping review is to identify the medical applications of passive infrared thermography and to catalogue the technical and environmental modalities. The diagnostic performance of thermography and the existence of specific reference data are evaluated, and research gaps and future tasks identified. The entire review process followed the Joanna Briggs Institute (JBI) approach and the results are reported according to PRISMA-ScR guidelines. The scoping review protocol is registered at the Open Science Framework (OSF). PubMed, CENTRAL, Embase, Web of Science, OpenGrey, OSF, and PROSPERO were searched using pretested search strategies based on the Population, Concept, Context (PCC) approach. According to the eligibility criteria, references were screened by two researchers independently. Seventy-two research articles were identified describing screening, diagnostic, or monitoring studies investigating the potential of thermography in a total of 17,314 participants within 38 different health conditions across 13 therapeutic areas. The use of several camera models from various manufacturers is described. These and other facts and figures are compiled and presented in a detailed, descriptive tabular and visual format. Thermography offers promising diagnostic capabilities, alone or in addition to conventional methods.

Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L variants, functional studies were performed in Drosophila and human cells. The fruit fly DOT1L ortholog, grappa, is expressed in most cells including neurons in the central nervous system. The identified DOT1L variants behave as gain-of-function alleles in flies and lead to increased H3K79 methylation levels in flies and human cells. Our results show that human DOT1L and fly grappa are required for proper development and that de novo heterozygous variants in DOT1L are associated with a Mendelian disease.

Reimagining Perinatal Palliative Care: A Broader Role for Support in the Face of Uncertainty.

Perinatal medicine is confronted by a growing number of complex fetal conditions that can be diagnosed prenatally. The evolution of potentially life-prolonging interventions for the baby before and after birth contributes to prognostic uncertainty. For clinicians who counsel families in these circumstances, determining which ones might benefit from early palliative care referral can be challenging. We assert that all women carrying a fetus diagnosed with a life-threatening condition for which comfort-focused care at birth is one ethically reasonable option ought to be offered palliative care support prenatally, regardless of the chosen plan of care. Early palliative care support can contribute to informed decision making, enhance psychological and grief support, and provide opportunities for care planning that includes ways to respect and honor the life of the fetus or baby, however long it may be.

Seasonal changes in the abundance and activity of bacterial and fungal denitrifying communities associated with different compost amendments.

Composts can be efficient organic amendments in potato culture as they can supply carbon and nutrients to the soil. However, more information is required on the effects of composts on denitrification and nitrous oxide emissions (N2O) and emission-producing denitrifying communities. The effects of three compost amendments (municipal source separated organic waste compost (SSOC), forestry waste mixed with poultry manure compost (FPMC), and forestry residues compost (FRC)) on fungal and bacterial denitrifying communities and activity was examined in an agricultural field cropped to potatoes during the fall, spring, and summer seasons. The denitrification enzyme activity (DEA), N2O emissions, and respiration were measured in parallel. N2O emission rates were greater in FRC-amended soils in the fall and summer, whereas soil respiration was highest in the SSOC-amended soil in the fall. A large number of nirK denitrifying fungal transcripts were detected in the fall, coinciding with compost application, while the greatest nirK bacterial transcripts were measured in the summer when plants were actively growing. Denitrifying community and transcript levels were poor predictors of DEA, N2O emissions, or respiration rates in compost-amended soil. Overall, the sampling date was driving the population and activity levels of the three denitrifying communities under study.

The Contribution of Family Medicine and Family Medicine Leaders to Primary Health Care Development in Americas - from Alma-Ata to Astana and beyond.

Since 2012, the Besrour Centre for Global Family Medicine at the College of Family Physician of Canada has brought together its partners from the Americas annually, to reflect on the evolution of Family Medicine on the continent since Alma-Ata, and to look forward to future challenges. Family doctors are but one element of a strong health system. Family Medicine provides key ingredients to respond to population health needs especially as countries move through the epidemiological transition to face larger burdens of chronic disease and multimorbidity. In this paper, we provide a high-level overview of the state of Family Medicine on the continent. We then analyze trends in the education of family physicians to face this changing landscape, including the emphasis on the leader role of future family physicians. Postgraduate programs in Family Medicine in the Americas are placing increasing emphasis on teaching collaborative care in view of creating truly interdisciplinary health teams for the benefit of patients.

The Contribution of Family Medicine and Family Medicine Leaders to Primary Health Care Development in Americas - from Alma-Ata to Astana and beyond / A contribuição da Medicina de Família e dos líderes em Medicina de Família para o desenvolvimento da Atenção Primária à Saúde nas Américas - de Alma-Ata à Astana e além

Abstract Since 2012, the Besrour Centre for Global Family Medicine at the College of Family Physician of Canada has brought together its partners from the Americas annually, to reflect on the evolution of Family Medicine on the continent since Alma-Ata, and to look forward to future challenges. Family doctors are but one element of a strong health system. Family Medicine provides key ingredients to respond to population health needs especially as countries move through the epidemiological transition to face larger burdens of chronic disease and multimorbidity. In this paper, we provide a high-level overview of the state of Family Medicine on the continent. We then analyze trends in the education of family physicians to face this changing landscape, including the emphasis on the leader role of future family physicians. Postgraduate programs in Family Medicine in the Americas are placing increasing emphasis on teaching collaborative care in view of creating truly interdisciplinary health teams for the benefit of patients.

Resumo Desde 2012, o Centro Besrour de Medicina Global de Família, na Faculdade de Medicina de Família do Canadá, reúne seus parceiros das Américas anualmente para refletir sobre a evolução da Medicina de Família no continente desde Alma-Ata e para os desafios futuros. Os médicos de família são apenas um elemento de um forte sistema de saúde. A Medicina de Família fornece ingredientes-chave para responder às necessidades de saúde da população, especialmente à medida em que os países passam pela transição epidemiológica para enfrentar um fardo maior de doenças crônicas e de multimorbidade. Neste artigo, fornecemos uma visão geral de alto nível do estado da Medicina de Família no continente. Em seguida, analisamos as tendências na educação dos médicos de família para enfrentar esse cenário em mudança, incluindo a ênfase no papel de líder dos futuros médicos de família. Os programas de pós-graduação em Medicina de Família nas Américas estão enfatizando cada vez mais o ensino do cuidado colaborativo, a fim de criar equipes de saúde verdadeiramente interdisciplinares para o benefício dos pacientes.

BCL2L1 is associated with γ-globin gene expression.

Fetal hemoglobin (HbF) expression is partially governed by the trans-acting quantitative trait loci BCL11A and MYB and a cis-acting locus linked to the HBB gene cluster. Our previous analysis of the Genotype-Tissue Expression database suggested that BCL2L1 was associated with HbF gene expression. In erythroid progenitors from patients with sickle cell disease, BCL2L1 messenger RNA (mRNA) levels were positively correlated with HBG mRNA and total HbF concentration (r2 = 0.72, P = .047 and r2 = 0.68, P = .01, respectively). Inhibition of BCL2L1 protein activity in HbF-expressing HUDEP-1 cells decreased HBG expression in a dose-dependent manner. Overexpression of BCL2L1 in these cells increased HBG expression fourfold (P < .05) and increased F cells by 13% (P < .05). Overexpression of BCL2L1 in erythroid progenitors derived from primary adult CD34+ cells upregulated HBG expression 11-fold (P < .05), increased F cells by 18% (P < .01), did not significantly affect cell differentiation or proliferation, and had a minor effect on survival. Although the mechanism remains unknown, our results suggest that BCL2L1 is associated with HbF gene activation.

De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies.

Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping phenotype of mild to severe intellectual disability. The de novo variants comprise six missense variants, three of which are recurrent, and three truncating variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants. MAPK8IP3 has been shown to be involved in the retrograde axonal-transport machinery, but many of its specific functions are yet to be elucidated. Using the CRISPR-Cas9 system to target six conserved amino acid positions in Caenorhabditis elegans, we found that two of the six investigated human alterations led to a significantly elevated density of axonal lysosomes, and five variants were associated with adverse locomotion. Reverse-engineering normalized the observed adverse effects back to wild-type levels. Combining genetic, phenotypic, and functional findings, as well as the significant enrichment of de novo variants in MAPK8IP3 within our total cohort of 27,232 individuals who underwent exome sequencing, we implicate de novo variants in MAPK8IP3 as a cause of a neurodevelopmental disorder with intellectual disability and variable brain anomalies.

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder.

Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects' cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis.

Patient Reported Outcomes After Radiation Therapy for Bone Metastases as a Function of Age: A Secondary Analysis of the NCIC CTG SC-Twenty-Three Randomized Trial.

PURPOSE: To explore the age difference in response and patient-reported outcomes in patients with cancer having bone metastases undergoing palliative radiotherapy. METHODS: Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life (QOL) Bone Metastases module (QLQ-BM22), EORTC QOL Core-15-Palliative (QLQ-C15-PAL), and Dexamethasone Symptom Questionnaire (DSQ) before a single 8-Gy radiation treatment, on days 10 and 42 after treatment. Patient demographics, performance status, analgesic consumption, BM22, C15, and DSQ were compared with multivariant analysis between patients under 75 years and 75 years and older. Multiple linear regression models were used to assess the differences between age-groups, adjusting for baseline demographics and primary disease sites. RESULTS: There were 298 patients (170 male) with 209 (70%) less than 75 years of age. Most common primary cancer sites include lung, prostate, and breast. At baseline, younger patients had better performance status, consumed more analgesic, and reported worse scores in nausea, insomnia, and functional interference, while older patients more commonly had prostate cancer. There were no significant differences in the incidence of radiation-induced pain flare; response to radiation; changes from baseline for BM22, C15-PAL; and DSQ, nor overall survival at day 42 between the 2 groups. Responders to radiation in the elderly group reported better improvement in physical and emotional domains when compared with nonresponders. CONCLUSIONS: In patients with cancer having bone metastases undergoing palliative radiotherapy, there was no significant difference in general with age in response to radiation and patient-reported outcomes. Palliative radiotherapy should be offered to elderly patients when needed.

Minimal clinically important differences in the EORTC QLQ-C30 and brief pain inventory in patients undergoing re-irradiation for painful bone metastases.

PURPOSE: The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools for measuring quality of life (QOL) and the impact of pain in patients with advanced cancer. Interpretation of these instrument scores can be challenging and it is difficult to know what numerical changes translate to clinically significant impact in patients' lives. To address this issue, our study sought to establish the minimal clinically important differences (MCID) for these two instruments in a prospective cohort of patients with advanced cancer and painful bone metastases. METHODS: Both anchor-based and distribution-based methods were used to estimate the MCID scores from patients enrolled in a randomized phase III trial evaluating two different re-irradiation treatment schedules. For the anchor-based method, the global QOL item from the QLQ-C30 was chosen as the anchor. Spearman correlation coefficients were calculated for all items and only those items with moderate or better correlation (|r| ≥ 0.30) with the anchor were used for subsequent analysis. A 10-point difference in the global QOL score was used to classify improvement and deterioration, and the MCID scores were calculated for each of these categories. These results were compared with scores obtained by the distribution-method, which estimates the MCID purely from the statistical characteristics of the sample population. RESULTS: A total of 375 patients were included in this study with documented pain responses and completed QOL questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI were found to have moderate or better correlation with the anchor. For deterioration, statistically significant MCID scores were found in all items of the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for deterioration were uniformly higher than the MCIDs for improvement. Using the distribution-based method, there was good agreement between the 0.5 standard deviation (SD) values and anchor-based scores for deterioration. For improvement, there was less agreement and the anchor-based scores were lower than the 0.5 SD values obtained from the distribution-based method. CONCLUSION: We present MCID scores for the QLQ-C30 and BPI instruments obtained from a large cohort of patients with advanced cancer undergoing re-irradiation for painful bone metastases. The results from this study were compared to other similar studies which showed larger MCID scores for improvement compared to deterioration. We hypothesize that disease trajectory and patient expectations are important factors in understanding the contrasting results. The results of this study can guide clinicians and researchers in the interpretation of these instruments.

Gender and age make no difference in the re-irradiation of painful bone metastases: A secondary analysis of the NCIC CTG SC.20 randomized trial.

BACKGROUND AND PURPOSE: Patient's gender and age may influence physicians in prescribing palliative radiotherapy. The purpose of this secondary analysis of the National Cancer Institute of Canada Clinical Trials Group Symptom Control Trial SC.20 was to explore the gender and age differences in pain and patient reported outcomes in cancer patients with bone metastases undergoing re-irradiation. MATERIALS AND METHODS: Response to radiation was evaluated using the International Bone Metastases Consensus Endpoint Definitions. Patients completed the Brief Pain Inventory (BPI) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (C30) before and 2 months after re-irradiation. RESULTS: A total of 847 patients were analyzed. At baseline, men had more dyspnea, and mild pain. Older patients consumed less analgesic. More women reported clinically significant improvement in mood and enjoyment of life in the BPI after radiation. Similarly, younger patients reported better improvement in enjoyment of life. There were no significant gender or age differences in overall survival, response to radiation, or in C30 scores at 2 months. CONCLUSION: Similar benefit in terms of pain relief was observed across all patient groups. Cancer patients with bone metastases should be offered palliative re-irradiation irrespective of gender or age. TRIAL REGISTRATION: NCT00080912; https://clinicaltrials.gov/ct2/show/NCT00080912.