Attitudes to the return of incidental and targeted genomic findings obtained in a high-risk pediatric cancer versus an inherited genetic condition research setting.

10066 Background: The disclosure of clinically significant, validated incidental and target findings to participants in genomic research is often recommended. There have been no reports on whether attitudes of parents differ if these findings emerge from an acquired pediatric cancer versus an inherited genetic condition setting. Methods: Parents in 3 large-scale projects [Canadian Pediatric Cancer Genome Consortium (CPCGC), the Finding of Rare Genes Canada Consortium (FORGE) and the Orphan Diseases: identifying Genes and Novel Therapeutics to Enhance Treatment Project (IGNITE)] were surveyed using a mailed, validated 29-item questionnaire. Two reminders were sent. Analysis was by descriptive and Chi-square statistics. Results: Response rate: 64% (n=307/480). 40% were > 50 yrs age; more than half had a grade 12 education. 86 were parents of poor risk pediatric cancer patients and 221 were parents or individuals with rare inherited conditions. Most stated a very strong or strong right to genomic research results, irrespective if from the target condition (97%) or incidental (86%). 70% wish genetic counselling pre- and post-research testing; an additional 20% were uncertain what this entails. Almost all indicated that genomic research for childhood onset conditions should occur, regardless of whether therapy existed (99%) or not (91%). A few indicated that they would not want incidental results showing an untreatable fatal condition (17%). Most want results, even if these suggest susceptibility to multiple conditions (87%) or are of uncertain health impact (84%). Most felt a right to genomic research that showed a serious condition in siblings, whether treatable (94%) or not (89%). 74% strongly support that results discovered after death of the proband be shared with family. Conclusions: Parents of children in both cancer and inherited rare conditions genomic research do not differ in indicating a strong right and desire to receive research results, even if they are of uncertain impact, of childhood onset, or after death of the proband. Clear delineation of what will or will not be offered from genomic research should be established at the time of consent.

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The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

Paediatrica Indonesiana ◽

10.14238/pi1.1.2018.42-7 ◽

2018 ◽

Vol 1 (1) ◽

pp. 42

Author(s):

Perjuangan Dapot Hamonangan Simbolon ◽

Selvi Nafianti ◽

Pertin Sianturi ◽

Bidasari Lubis ◽

Aznan Lelo

Keyword(s):

Placebo Group ◽

Cancer Patients ◽

Pediatric Cancer ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Chi Square ◽

Double Blind ◽

Significant Difference ◽

Pediatric Cancer Patients

Background Chemotherapy-induced nausea and vomiting are some of the most disturbing side effects in pediatric cancer patients. The standard recommendation is the use of 5-hydroxytryptamine 3 receptor antagonist, such as ondansetron, to treat these symptoms. Despite this treatment, more than 50% of patients still experience nausea and vomiting.Objective To evaluate the effect of the addition of omeprazole to ondansetron in the treatment of chemotherapy-induced nausea and vomiting.Methods A double-blind, randomized, controlled trial was conducted at Haji Adam Malik Hospital, Medan, North Sumatera, from March to May 2016. Subjects were children aged 1 to 18 years, diagnosed with cancer, and who received intravenous chemotherapy. Patients were randomized to receive either a single dose of ondansetron (0.5 mg/kg) plus placebo or ondansetron (0.5 mg/kg) plus omeprazole (0.5 mg/kg). The severity of nausea and vomiting were measured using the Rhodes index of nausea, vomiting, and retching during the 24 hours after initiation of emetogenic chemotherapy. The primary outcome of efficacy was the proportion of patients who achieved complete response (lack of nausea/vomiting). Statistical analysis was performed by Chi-square and Fischer’s exact tests.Results Seventy eligible pediatric patients were randomized into two groups: 32 subjects in the ondansetron + placebo group and 38 others in the ondansetron + omeprazole group. The therapy failed in 50% (16/32) of the ondansetron + placebo group and 18.4% (7/38) of the ondansetron + omeprazole group. There was a significant difference in the clinical response between groups (P=0.01).Conclusion The addition of omeprazole to ondansetron for the treatment of chemotherapy-induced nausea and vomiting is more effective than administration of ondansetron alone.

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AKTIVITAS FISIK DAN TINGKAT DEPRESI LANSIA DI MASA PANDEMI

JURNAL KESEHATAN MERCUSUAR ◽

10.36984/jkm.v4i2.222 ◽

2021 ◽

Vol 4 (2) ◽

pp. 11-18

Author(s):

Yunita Sari

Keyword(s):

Physical Activity ◽

Large Scale ◽

Geriatric Depression Scale ◽

Depression Scale ◽

The Elderly ◽

P Value ◽

Chi Square ◽

Cross Sectional ◽

Social Restriction ◽

Almost All

COVID-19 has caused a pandemic in almost all parts of the world, including Indonesia. This has led to lockdown conditions in various countries. The Indonesian government is trying to break the chain of transmission of Covid-19, one of which is the Large-Scale Social Restriction (PSBB) which limits social and physical activities. One of the people affected by this policy is the elderly. Various studies have stated that physical activity will affect cognitive function and the level of depression in the elderly. The purpose of this study is to determine the relationship between physical activity and the level of depression in the elderly during a pandemic. This research is a descriptive corelative study with a cross sectional approach. Data were collected using A Physical Activity for the Elderly questionnaire to measure the physical activity in the elderly, and Geriatric Depression Scale to measure the level of depression. Bivariate statistical test using chi square. The results showed that there was no relationship between the level of physical activity and depression in the elderly during the pandemic (p value > 0.05).

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Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): A Cloud-based Platform for Curating and Classifying Germline Variants

10.1101/340901 ◽

2018 ◽

Author(s):

Michael N. Edmonson ◽

Aman N. Patel ◽

Dale J. Hedges ◽

Zhaoming Wang ◽

Evadnie Rampersaud ◽

...

Keyword(s):

Pediatric Cancer ◽

Information Exchange ◽

Large Scale ◽

Disease Genes ◽

Single Nucleotide Variants ◽

Web Based ◽

Pediatric Cancer Patients ◽

Predisposition Genes ◽

Next Generation Sequencing Ngs

AbstractVariant interpretation in the era of next-generation sequencing (NGS) is challenging. While many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here we present “PeCanPIE” – the Pediatric Cancer Variant Pathogenicity Information Exchange, a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in Variant Call Format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4,000 pediatric cancer patients, and serves as a repository for the expert-reviewed results. While PeCanPIE’s web-based interface was designed to be accessible to non-bioinformaticians, its back end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.

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Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Santé cohort

Scientific Reports ◽

10.1038/s41598-021-98496-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eloi Chazelas ◽

Nathalie Druesne-Pecollo ◽

Younes Esseddik ◽

Fabien Szabo de Edelenyi ◽

Cédric Agaesse ◽

...

Keyword(s):

Large Scale ◽

Monosodium Glutamate ◽

Food Additives ◽

Experimental Studies ◽

Health Impact ◽

Potassium Nitrate ◽

Population Based ◽

Food Additive ◽

Potassium Sorbate ◽

Chi Square

AbstractFood additives (e.g. artificial sweeteners, emulsifiers, dyes, etc.) are ingested by billions of individuals daily. Some concerning results, mainly derived from animal and/or cell-based experimental studies, have recently emerged suggesting potential detrimental effects of several widely consumed additives. Profiles of additive exposure as well as the potential long-term impact of multiple exposure on human health are poorly documented. This work aimed to estimate the usual intake of food additives among participants of the French NutriNet-Santé cohort and to identify and describe profiles of exposure (single substances and mixtures). Overall, 106,489 adults from the French NutriNet-Santé cohort study (2009-ongoing) were included. Consumption of 90 main food additives was evaluated using repeated 24 h dietary records including information on brands of commercial products. Qualitative information (as presence/absence) of each additive in food products was determined using 3 large-scale composition databases (OQALI, Open Food Facts, GNPD), accounting for the date of consumption of the product. Quantitative ingested doses were estimated using a combination of laboratory assays on food matrixes (n = 2677) and data from EFSA and JECFA. Exposure was estimated in mg per kg of body weight per day. Profiles of exposure to food additive mixtures were extracted using Non-negative Matrix Factorization (NMF) followed by k-means clustering as well as Graphical Lasso. Sociodemographic and dietary comparison of clusters of participants was performed by Chi-square tests or linear regressions. Data were weighted according to the national census. Forty-eight additives were consumed by more than 10% of the participants, with modified starches and citric acid consumed by more than 90%. The top 50 also included several food additives for which potential adverse health effects have been suggested by recent experimental studies: lecithins (86.6% consumers), mono- and diglycerides of fatty acids (78.1%), carrageenan (77.5%), sodium nitrite (73.9%), di-, tri- and polyphosphates (70.1%), potassium sorbate (65.8%), potassium metabisulphite (44.8%), acesulfame K (34.0%), cochineal (33.9%), potassium nitrate (31.6%), sulfite ammonia caramel (28.8%), bixin (19.5%), monosodium glutamate (15.1%) and sucralose (13.5%). We identified and described five clusters of participants more specifically exposed to five distinct additive mixtures and one additional cluster gathering participants with overall low additive exposure. Food additives, including several for which health concerns are currently debated, were widely consumed in this population-based study. Furthermore, main mixtures of additives were identified. Their health impact and potential cocktail effects should be explored in future epidemiological and experimental studies.

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The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

Paediatrica Indonesiana ◽

10.14238/pi58.1.2018.42-7 ◽

2018 ◽

Vol 58 (1) ◽

pp. 42

Author(s):

Perjuangan Dapot Hamonangan Simbolon ◽

Selvi Nafianti ◽

Pertin Sianturi ◽

Bidasari Lubis ◽

Aznan Lelo

Keyword(s):

Placebo Group ◽

Cancer Patients ◽

Pediatric Cancer ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Chi Square ◽

Double Blind ◽

Significant Difference ◽

Pediatric Cancer Patients

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Pharmacogenetics of Antidepressants: from Genetic Findings to Predictive Strategies

Acta biomedica scientifica ◽

10.29413/abs.2019-4.2.5 ◽

2019 ◽

Vol 4 (2) ◽

pp. 33-43

Author(s):

L. K. Khokhlov ◽

N. E. Lukyanov

Keyword(s):

Large Scale ◽

Depressive Disorders ◽

Genome Wide Association Study ◽

Treatment Effectiveness ◽

Predictive Biomarkers ◽

Genomic Research ◽

Control Group ◽

Variable Activity ◽

Cytochrome P450 Family ◽

Almost All

The constantly growing contribution of depressive disorders to the global disease statistics calls for a growth of treatment effectiveness and optimization. Antidepressants are the most frequently prescribed medicines for depressive disorders. However, development of a standardized pharmacotherapeutic approach is burdened by the genomic heterogeneity, lack of reliable predictive biomarkers and variability of the medicines metabolism aggravated by multiple side effects of antidepressants. According to modern assessments up to 20 % of the genes expressed in our brain are involved in the pathogenesis of depression. Large-scale genetic and genomic research has found a number of potentially prognostic genes. It has also been proven that the effectiveness and tolerability of antidepressants directly depend on the variable activity of the enzymes that metabolize medicines. Almost all modern antidepressants are metabolized by the cytochrome P450 family enzymes. The most promising direction of research today is the GWAS (Genome-Wide Association Study) method that is aimed to link genomic variations with phenotypical manifestations. In this type of research genomes of depressive patients with different phenotypes are compared to the genomes of the control group containing same age, sex and other parameters healthy people. Notably, regardless of the large cohorts of patients analyzed, none of the GWA studies conducted so far can reliably reproduce the results of other analogous studies. The explicit heterogeneity of the genes associated with the depression pathogenesis and their pleiotropic effects are strongly influenced by environmental factors. This may explain the difficulty of obtaining clear and reproducible results. However, despite any negative circumstances, the active multidirectional research conducted today, raises the hope of clinicians and their patients to get a whole number of schedules how to achieve remission faster and with guaranteed results

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Characteristics of Traditional Chinese Medicine Use in Pediatric Cancer Patients: A Nationwide, Retrospective, Taiwanese-Registry, Population-Based Study

Integrative Cancer Therapies ◽

10.1177/1534735416659357 ◽

2016 ◽

Vol 16 (2) ◽

pp. 147-155 ◽

Cited By ~ 15

Author(s):

Hung-Rong Yen ◽

Wan-Yu Lai ◽

Chih-Hsin Muo ◽

Mao-Feng Sun

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Cancer Patients ◽

Pediatric Cancer ◽

Large Scale ◽

Herbal Remedies ◽

Research Database ◽

Children With Cancer ◽

Significant Difference ◽

Pediatric Cancer Patients

Background. Large-scale surveys of complementary traditional Chinese medicine (TCM) use in pediatric cancer patients are lacking. The aim of our study was to investigate the use of TCM in pediatric cancer patients. Methods. We analyzed cancer patients younger than 18 years (n = 12 965) who were registered in the National Health Insurance Research Database in Taiwan between 2001 and 2011. Patients were categorized into TCM or non–TCM users based on their use of TCM. Results. In Taiwan, 8086 (62.4%) children with cancer sought TCM treatment at some point. Children in older age groups, including school-aged children and adolescents, were more likely to use TCM. There was no significant difference in the distributions of gender and urbanization. The 3 most common diseases for which TCM users visited the clinic were neoplasm (33.2%), respiratory system disease (32.9%), and infectious disease (8.86%). The most commonly utilized TCM therapy was Chinese herbal remedies. Patients who had comorbid conditions such as allergic rhinitis, dyspepsia, disorders of menstruation, and disease of the musculoskeletal system and connective tissue tended to visit TCM clinics. Conclusions. Adjunctive TCM use is not low in Taiwanese children with cancer. Further studies to investigate the efficacy and safety of TCM in children with cancer are warranted.

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Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes

PLoS Genetics ◽

10.1371/journal.pgen.1009231 ◽

2020 ◽

Vol 16 (12) ◽

pp. e1009231

Author(s):

Anna Byrjalsen ◽

Thomas V. O. Hansen ◽

Ulrik K. Stoltze ◽

Mana M. Mehrjouy ◽

Nanna Moeller Barnkob ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Cancer Patients ◽

Genome Sequencing ◽

Pediatric Cancer ◽

Population Based ◽

Whole Genome ◽

Adult Onset ◽

Childhood Onset ◽

Children With Cancer ◽

Pediatric Cancer Patients

PURPOSE: Historically, cancer predisposition syndromes (CPSs) were rarely established for children with cancer. This nationwide, population-based study investigated how frequently children with cancer had or were likely to have a CPS. METHODS: Children (0–17 years) in Denmark with newly diagnosed cancer were invited to participate in whole-genome sequencing of germline DNA. Suspicion of CPS was assessed according to Jongmans’/McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) criteria and familial cancer diagnoses were verified using population-based registries. RESULTS: 198 of 235 (84.3%) eligible patients participated, of whom 94/198 (47.5%) carried pathogenic variants (PVs) in a CPS gene or had clinical features indicating CPS. Twenty-nine of 198 (14.6%) patients harbored a CPS, of whom 21/198 (10.6%) harbored a childhood-onset and 9/198 (4.5%) an adult-onset CPS. In addition, 23/198 (11.6%) patients carried a PV associated with biallelic CPS. Seven of the 54 (12.9%) patients carried two or more variants in different CPS genes. Seventy of 198 (35.4%) patients fulfilled the Jongmans’ and/or MIPOGG criteria indicating an underlying CPS, including two of the 9 (22.2%) patients with an adult-onset CPS versus 18 of the 21 (85.7%) patients with a childhood-onset CPS (p = 0.0022), eight of the additional 23 (34.8%) patients with a heterozygous PV associated with biallelic CPS, and 42 patients without PVs. Children with a central nervous system (CNS) tumor had family members with CNS tumors more frequently than patients with other cancers (11/44, p = 0.04), but 42 of 44 (95.5%) cases did not have a PV in a CPS gene. CONCLUSION: These results demonstrate the value of systematically screening pediatric cancer patients for CPSs and indicate that a higher proportion of childhood cancers may be linked to predisposing germline variants than previously supposed.

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