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1.
Artigo em Inglês | MEDLINE | ID: mdl-32008974

RESUMO

OBJECTIVE: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada. METHODS: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions. RESULTS: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost. CONCLUSIONS: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.

2.
J Pediatr Nurs ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32007328

RESUMO

PURPOSE: To examine the turnover intention of Chinese pediatric nurses, its influential socio-demographic factors, and the association with calling and job satisfaction. DESIGN AND METHODS: We randomly surveyed 10% of the nurses from 50% of the children's tertiary hospitals nationwide in China. Data were collected on nurses' turnover intention and associated factors such as age, income, skill level, working years, job satisfaction, and calling in 2017. RESULTS: In total, 547 nurses were surveyed, and the response rate was 98.6%. More than a third of pediatric nurses had the intention to quit their current jobs. Influential factors associated with turnover intention included position, skill level, calling, and job satisfaction. Low job satisfaction of administration, workload, relationships with colleagues, work itself, and remuneration and benefits were negatively associated with turnover intention, with the odds ratio of high turnover intention in the lowest level of satisfaction ranging from 2.0-7.8 when compared with the medium level. However, calling was the strongest factor influencing turnover intention, and a weak calling may increase the risk of high turnover intention more than ten times, after adjusting for job satisfaction. Job satisfaction may partially mediate the relationship between calling and turnover intention. CONCLUSION: The turnover intention of nurses was high in Chinese pediatric tertiary hospital. Calling may be the strongest influential factor of turnover intention. PRACTICE IMPLICATIONS: To alleviate pediatric nurses' turnover rate, it may be helpful to develop interventions to increase job satisfaction and calling.

3.
Syst Rev ; 9(1): 20, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996261

RESUMO

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

4.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 203-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31795923

RESUMO

Since the inception of the IARC Monographs Programme in the early 1970s, this Programme has developed 119 Monograph Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the Monographs, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with sufficient evidence (82 agents) or limited evidence (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the IARC Monographs, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and γ-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the IARC Monographs did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for sufficient evidence of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.

5.
Gut ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818908

RESUMO

OBJECTIVE: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). DESIGN: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as 'positive' and 'less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. RESULTS: We initially identified 18 independent variants at 16 loci that were classified as 'positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as 'less-credible positive' SNPs; 72.2% of the 'positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to 'less-credible' positive (reducing the 'positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-analyses found no evidence to support their associations with CRC risk. CONCLUSION: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.

6.
Sci Rep ; 9(1): 15704, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673070

RESUMO

Hypoxic ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. Our study sought to examine whether patterns of newborn screening analytes differed between infants with and without neonatal HIE in order to identify opportunities for potential use of these analytes for diagnosis in routine clinical practice. We linked a population-based newborn screening registry with health databases to identify cases of HIE among term infants (≥37 weeks' gestation) in Ontario from 2010-2015. Correlations between HIE and screening analytes were examined using multivariable logistic regression models containing clinical factors and individual screening analytes (acyl-carnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes). Among 731,841 term infants, 3,010 were diagnosed with HIE during the neonatal period. Multivariable models indicated that clinical variables alone or in combination with hemoglobin values were not associated with HIE diagnosis. Although the model was improved after adding acyl-carnitines and amino acids, the ability of the model to identify infants with HIE was moderate. Our findings indicate that analytes associated with catabolic stress were altered in infants with HIE; however, future research is required to determine whether amino acid and acyl-carnitine profiles could hold clinical utility in the early diagnosis or clinical management of HIE. In particular, further research should examine whether cord blood analyses can be used to identify HIE within a clinically useful timeframe or to guide treatment and predict long-term health outcomes.

7.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 244-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637961

RESUMO

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.

8.
Can J Neurol Sci ; 46(6): 717-726, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31387656

RESUMO

BACKGROUND: An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care. METHODS: We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities. RESULTS: We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend "mitochondrial cocktails" for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority. CONCLUSIONS: While Canadian physicians' views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.

9.
Ann Epidemiol ; 37: 57-63.e3, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387776

RESUMO

PURPOSE: We studied whether having an infant with birth defects was associated with the risk of maternal cancer. METHODS: We carried out a longitudinal cohort study of 1,214,506 women who delivered infants between 1989 and 2016 in Quebec, Canada. We identified women whose infants had birth defects and followed the mothers over time to identify cancers up to 28 years after delivery. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between birth defects and maternal cancer, adjusted for maternal characteristics. RESULTS: A total of 36,050 women developed cancer during 19,251,851 person-years of follow-up. Relative to no birth defects, women whose infants had defects did not have an elevated risk of cancer overall (HR 1.03, 95% CI 0.99-1.06). However, associations were present with placental cancer (HR 2.23, 95% CI 1.04-4.77) and lymphoid leukemia (HR 1.61, 95% CI 1.03-2.51). Among specific birth defects, women whose infants had heart (HR 1.12, 95% CI 1.03-1.21) or sensory (HR 1.16, 95% CI 1.04-1.30) defects had a higher risk of cancer. CONCLUSIONS: We found inconsistent evidence of a clinically meaningful association between having an infant with birth defects and the risk of early maternal cancer.

10.
Expert Rev Proteomics ; 16(9): 727-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422714

RESUMO

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening. Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model's performance through internal and external validation studies, and through implementation of the model internationally. Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.

11.
J Eval Clin Pract ; 25(6): 1169-1181, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423705

RESUMO

OBJECTIVE: The objective of the present study is to describe the development and field testing of a preference-elicitation tool for cervical cancer screening, meeting International Patient Decision Aids Standards (IPDAS) quality criteria. METHODS: We developed a tool designed to elicit women's preferences among cervical cancer screening modalities. The Ottawa Decision Support Framework and IPDAS systematic development process guided the design, and we followed IPDAS criteria for conducting a field test in a real-world setting. Using social media recruitment strategies, we identified a convenience sample of Ontario women who were currently eligible for cervical screening to test the tool. We evaluated the feasibility, acceptability, balance of information, and ability to elicit women's informed, values-based preferences using an online survey embedded in the tool. RESULTS: Twenty-five women participated in the field test. Participants were aged 20 to 63 years , and identified as predominantly white (88%), living in Northern Ontario (68%), and most had university education (75%). Most participants (72%) considered the length of the website as "just right," and 100% indicated that they would find the tool useful for decision-making. Over two-thirds (68%) of participants perceived the information in the tool as "balanced." Almost all (92%) participants scored at least 4 out of 7 on the knowledge quiz, and most participants (84%) selected their preference in an informed, values-based way. CONCLUSION: The results from our field test of this tool provide preliminary evidence of the tool's feasibility, acceptability, balance, and ability to elicit women's informed, values-based preferences among available cervical screening modalities. Further research should elicit the distribution of preferences of cervical screening modalities in other regions, using a sample who represents the screening population and a rigorous study design. It will be important for researchers and screening programmes to evaluate the tool's ability to elicit women's informed, values-based preferences compared with educational materials.

12.
BMC Pregnancy Childbirth ; 19(1): 252, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324151

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Screening for GDM and applying adequate interventions may reduce the risk of adverse outcomes. However, the diagnosis of GDM depends largely on tests performed in late second trimester. The aim of the present study was to bulid a simple model to predict GDM in early pregnancy in Chinese women using biochemical markers and machine learning algorithm. METHODS: Data on a total of 4771 pregnant women in early gestation were used to fit the GDM risk-prediction model. Predictive maternal factors were selected through Bayesian adaptive sampling. Selected maternal factors were incorporated into a multivariate Bayesian logistic regression using Markov Chain Monte Carlo simulation. The area under receiver operating characteristic curve (AUC) was used to assess discrimination. RESULTS: The prevalence of GDM was 12.8%. From 8th to 20th week of gestation fasting plasma glucose (FPG) levels decreased slightly and triglyceride (TG) levels increased slightly. These levels were correlated with those of other lipid metabolites. The risk of GDM could be predicted with maternal age, prepregnancy body mass index (BMI), FPG and TG with a predictive accuracy of 0.64 and an AUC of 0.766 (95% CI 0.731, 0.801). CONCLUSIONS: This GDM prediction model is simple and potentially applicable in Chinese women. Further validation is necessary.


Assuntos
Diabetes Gestacional , Programas de Rastreamento/métodos , Primeiro Trimestre da Gravidez/sangue , Medição de Risco/métodos , Adulto , Glicemia/análise , Índice de Massa Corporal , China/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Idade Materna , Valor Preditivo dos Testes , Gravidez , Prognóstico , Fatores de Risco
13.
Eur J Hum Genet ; 27(11): 1701-1715, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31231136

RESUMO

We compared clinical validity of two non-invasive prenatal screening (NIPS) methods for fetal trisomies 13, 18, 21, and monosomy X. We recruited prospectively 2203 women at high risk of fetal aneuploidy and 1807 at baseline risk. Three-hundred and twenty-nine euploid samples were randomly removed. The remaining 1933 high risk and 1660 baseline-risk plasma aliquots were assigned randomly between four laboratories and tested with two index NIPS tests, blind to maternal variables and pregnancy outcomes. The two index tests used massively parallel shotgun sequencing (semiconductor-based and optical-based). The reference standard for all fetuses was invasive cytogenetic analysis or clinical examination at birth and postnatal follow-up. For each chromosome of interest, chromosomal ratios were calculated (number of reads for chromosome/total number of reads). Euploid samples' mean chromosomal ratio coefficients of variation were 0.48 (T21), 0.34 (T18), and 0.31 (T13). According to the reference standard, there were 155 cases of T21, 49 T18, 8 T13 and 22 45,X. Using a fetal fraction ≥4% to call results and a chromosomal ratio z-score of ≥3 to report a positive result, detection rates (DR), and false positive rates (FPR) were not statistically different between platforms: mean DR 99% (T21), 100%(T18, T13); 79%(45,X); FPR < 0.3% for T21, T18, T13, and <0.6% for 45,X. Both methods' negative predictive values in high-risk pregnancies were >99.8%, except for 45,X(>99.6%). Threshold analysis in high-risk pregnancies with different fetal fractions and z-score cut-offs suggested that a z-score cutoff to 3.5 for positive results improved test accuracy. Both sequencing platforms showed equivalent and excellent clinical validity.

14.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31253739

RESUMO

OBJECTIVES: Although it is widely believed that China is facing a major shortage of pediatricians, the real situation of the current national status of pediatric human resources and their working conditions has not been evaluated to date. METHODS: We administered a survey to 54 214 hospitals from all 31 provinces in mainland China from 2015 to 2016. Hospital directors of all secondary and tertiary hospitals with pediatric services and a random sample (10%) of primary hospitals provided information on number of pediatricians and their educational levels, specialties, workloads, dropout rates, and other hospital characteristics. A data set of medical resources and socioeconomic information regarding each region (1997-2016) was constructed from the Chinese National Statistics Bureau. The Gini coefficient was used to describe the geographical distributions of pediatricians and hospitals. RESULTS: There were 135 524 pediatricians in China or ∼4 pediatricians per 10 000 children. Pediatricians' average educational level was low, with ∼32% having only 3 years of junior college training after high school. The distribution of pediatricians was extremely skewed (Gini coefficient 0.61), and the imbalance of highly educated pediatricians was even more skewed (Gini coefficient 0.68). The dropout rate of pediatricians was 12.6%. Despite an increase in the Chinese government's financial investment in health over the last decade, physicians have been burdened with a greater workload. CONCLUSIONS: Uneven development of the pediatric care system, inadequately trained pediatricians, low job satisfaction, and unmet demand for pediatric care are the major challenges facing China's pediatric health care system.


Assuntos
Área Carente de Assistência Médica , Pediatras/provisão & distribução , Carga de Trabalho/estatística & dados numéricos , Adulto , China , Estudos Transversais , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Pediatras/educação
15.
Oral Dis ; 25(6): 1668-1671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31161688

RESUMO

OBJECTIVE: To investigate the influence of MTHFR c.677C>T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL). METHODS: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE-1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C>T genotyping was carried out using the TaqMan genotyping assay. RESULTS: LINE-1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p = 0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C>T genotyping revealed that the difference in LINE-1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C>T and was not apparent in TT homozygous cases (p = 0.027). CONCLUSION: This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C>T genotype in establishing this difference.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Estudos de Casos e Controles , Metilação de DNA , Genótipo , Humanos , Lactente , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
16.
J Matern Fetal Neonatal Med ; : 1-4, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31046492

RESUMO

OBJECTIVE: To assess whether newborn screening analytes could be utilized beyond their traditional application to identify infants at high risk of mortality within the first 6 months of life. METHODS: We linked a province-wide newborn screening registry with health administrative databases to identify infant deaths within 6 months in a source population of live-born infants between 2010 and 2014. We used a nested case-control study design, in which all infant deaths between 7 days and 6 months of age were included as cases, and a random sample of infants from the source population were selected as controls and were matched to cases at a ratio of 10:1. We examined the association between mortality and screening analytes (acylcarnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes) using lasso regression to fit multivariable models. RESULTS: Among 350 infant deaths between 7 days and 6 months of age, and 3498 matched controls with complete data, our multivariable model demonstrated only modest ability to identify infant deaths (optimism-corrected c-statistic: 0.61, 95% confidence interval: 0.50-0.71). CONCLUSION: We did not find newborn screening analytes to be strongly predictive of infant mortality between 7 days and 6 months of age in the general population of newborns. Future studies should investigate whether predictive modeling within more homogeneous cause-of-death categories could lead to improved predictive ability for infant mortality.

17.
Lancet Child Adolesc Health ; 3(5): 332-342, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30872112

RESUMO

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

18.
Nutrition ; 61: 208-212, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30822753

RESUMO

OBJECTIVES: The genetics of binge-eating disorder (BED) is an emerging topic and one candidate pathway, namely the fat mass and obesity-associated (FTO) gene, may be implicated because of its role in food reward sensitivity and self-regulation of eating. The aims of this study were to examine the independent effects of variants of FTO on binge frequency in women with and without BED and to examine the moderating role of interpersonal attachment in this association. METHODS: Secondary data analysis was conducted on a cross-sectional comparison of three groups of women in a trial of group treatment for BED: BED with obesity (n = 73), BED without obesity (n = 55), and normal weight without BED (n = 50). Women were genotyped for five of the most common FTO single-nucleotide polymorphisms, rs9939609, rs8050136, rs3751812, rs1421085, and rs1121980, which have been related to body mass index and energy intake. Binge frequency (Eating Disorder Examination), body composition (bioelectric impedance), and attachment (Attachment Style Questionnaire) were assessed. RESULTS: There were no significant between-group differences for frequencies of FTO alleles, nor were there any significant anthropometric associations. The FTO × attachment interaction was significant whereby, relative to a low-risk FTO genotype, individuals with a high-risk genotype for the SNP rs1421085 and high-avoidant attachment had higher mean binge frequency than those with high genetic risk but low-avoidant attachment (ß = -7.96; t = -2.07; P = 0.042). CONCLUSIONS: FTO genotypes associated with risk for obesity and loss of control of eating, specifically rs1421085, may interact with insecure attachment in a way that may exacerbate binge eating among women with BED.

19.
Elife ; 82019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30887951

RESUMO

This study sought to evaluate the performance of metabolic gestational age estimation models developed in Ontario, Canada in infants born in Bangladesh. Cord and heel prick blood spots were collected in Bangladesh and analyzed at a newborn screening facility in Ottawa, Canada. Algorithm-derived estimates of gestational age and preterm birth were compared to ultrasound-validated estimates. 1036 cord blood and 487 heel prick samples were collected from 1069 unique newborns. The majority of samples (93.2% of heel prick and 89.9% of cord blood) were collected from term infants. When applied to heel prick data, algorithms correctly estimated gestational age to within an average deviation of 1 week overall (root mean square error = 1.07 weeks). Metabolic gestational age estimation provides accurate population-level estimates of gestational age in this data set. Models were effective on data obtained from both heel prick and cord blood, the latter being a more feasible option in low-resource settings.

20.
Paediatr Perinat Epidemiol ; 33(2): 145-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30920008

RESUMO

BACKGROUND: We sought to assess the recent trend in NTD prevalence at birth in the post-folic acid food fortification era and to identify the maternal risk factors associated with that trend. METHODS: We carried out a population-based study of all livebirths and stillbirths (including late pregnancy terminations) delivered in hospitals in Canada (excluding Quebec) from 2004 to 2015 (n = 3 439 330). We examined NTD birth prevalence by year, multiple pregnancy, maternal age, parity, pregestational diabetes, chronic illness, and problematic substance use. Poisson regression was used to quantify the association between spina bifida and cranial defects and maternal characteristics and other risk factors. RESULTS: We identified 1517 non-chromosomal NTDs, yielding a birth prevalence of 4.4 per 10 000 total births. NTD prevalence rose from 3.6 in 2004 to 4.6 per 10 000 in 2015 (Ptrend  = 0.03). Among NTD subtypes, only spina bifida showed a temporal increase (Ptrend  = 0.03). Birth prevalence of spina bifida was higher among younger mothers, those with type 2 diabetes (rate ratio (RR) 3.74, 95% confidence interval (CI) 2.21, 6.35), chronic illness (RR 3.16, 95% CI 1.97, 5.07), and problematic substance use (RR 1.88, 95% CI 1.31, 2.71). Adjusting for risk factors attenuated the significant temporal trend in spina bifida (unadjusted average annual prevalence ratio (aAAPR) 1.016, 95% CI 1.001, 1.032; adjusted AAPR 1.014, 95% CI 0.998, 1.029). CONCLUSIONS: Increases in the frequency of maternal risk factors such as pregestational diabetes mellitus, substance use, and chronic illness may be partly responsible for the recent rise in NTDs, particularly spina bifida.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Ácido Fólico/uso terapêutico , Mães , Defeitos do Tubo Neural/epidemiologia , Gravidez em Diabéticas/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Recém-Nascido , Idade Materna , Defeitos do Tubo Neural/etiologia , Vigilância da População , Gravidez , Gravidez em Diabéticas/fisiopatologia , Prevalência , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
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