Quel impact de la RCMI des carcinomes nasopharyngés sur les structures glandulaires ?

PurposeThe aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts.Patients and methodsTwenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38 Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary).ResultsWe observed a decrease in the volume of right and left parotids (− 27.9% and − 27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was − 36.1% on the right and − 27.28% on the left. The value of reduction of the thyroid gland was − 18.01%. A medial supra-millimeter migration of 2 and 1.15 mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8 ± 2.3 Gy for the right and 1.5 ± 2.7 Gy for the left. For the right sub maxillary gland, the increase was about 0.35 ± 2 Gy and 3.79 ± 5.2 Gy for the thyroid.ConclusionThe modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.     

Objective and subjective measures of the neighbourhood environment: Associations with frailty levels

ObjectivesThe aim of this study was to investigate whether perceptions of the neighbourhood environment (NE) and objective measures of the NE were associated with frailty in older adults.MethodsA cross-sectional study in Adelaide, Australia, recruited a sample of 115 community-dwelling adults aged ≥60 years. Respondents’ perceptions of their NEs were assessed using the Neighbourhood Environment Walkability Scale (NEWS). An objective assessment of these NEWS survey questions was conducted using seven variables: residential density, land use mix diversity, street connectivity, accessibility, seasonal persistent green cover, road crash density and crime rate. Frailty was evaluated using the FRAIL (fatigue, resistance, ambulation, illnesses and loss of weight) scale. Multivariable linear regression analyses were employed to assess the associations between NEWS and frailty, and to assess the associations between objective neighbourhood variables and frailty.ResultsFrail and pre-frail older adults were more likely to live in areas with lower residential density, lower density of road crashes, and higher accessibility than robust participants. Additionally, a poorer perception of the overall environment, worse land-use mix and accessibility and worse crime safety were associated with frailty and pre-frailty after adjustment of covariates and objective GIS variables.DiscussionNeighbourhood characteristics, both objective and perceived, are associated with frailty levels in older adults, and that strategies to tackle frailty must consider the impact of the neighbourhood environment.     

Strategies to optimize comprehension of numerical medication instructions: A systematic review and concept map

ObjectiveTo develop evidence-based recommendations for improving comprehension of quantitative medication instructions.MethodsThis review included a literature search from inception to November 2021. Studies were included for the following: 1) original research; 2) compared multiple formats for presenting quantitative medication information on dose, frequency, and/or time; 3) included patients/lay-people; 4) assessed comprehension-related outcomes quantitatively. To classify the studies, we developed a concept map. We weighed 3 factors (risk of bias in individual studies, consistency of findings among studies, and homogeneity of the interventions tested) to generate 3 levels of recommendations.ResultsTwenty-one studies were included. Level 1 recommendations are: 1) use visualizations of medication doses for liquid medications, and 2) express instructions in time-periods rather than times per day. Level 2 recommendations include: validate icons, use panels or tables with explanatory text, use visualizations for non-English speaking populations and for those with low health literacy and limited English proficiency.ConclusionsVisualized liquid medication doses and time period-based administration instructions improve comprehension of numerical medication instructions. Use of visualizations for those with limited health literacy and English proficiency could result in improved outcomes.Practice implicationsPractitioners should use visualizations for liquid medication instructions and time period-based instructions to improve outcomes.     

(Pre)Modern sleep. New evidence from the Antwerp criminal court (1715–1795)

Lately, experts have turned to historical evidence to uncover the default mode of our sleep pattern. Even though there are some notable exceptions, most historians use a qualitative methodology based on scattered evidence in diaries, letters, novels, medical treatise and other literary sources. To provide fresh perspective in the debate, the present article develops a more quantitative approach. Drawing fresh evidence from early modern criminal records – viz the eyewitness reports of the Hoge Vierschaer or the local criminal court in Antwerp – we are able to debunk some classic stereotypes about premodern sleep patterns. Data reveal that most 18^th‐century Antwerpers slept fewer hours than we would expect, slumbered in a monophasic way and rarely if ever took a nap during the day. Moreover, the start and end of sleep were less attuned to the solar cycle than we would imagine. Last but not least, the pattern also shows some fascinating weekly and seasonal variations.     

Cytochrome P450 2C19 enzyme,Cytochrome P450 2C9 enzyme,and Cytochrome P450 2D6 enzyme allelic variants and its possible effect on drug metabolism: A retrospective study

The objective of the present study was to assess the allelic variations of Cytochrome P450 (CYP) enzymes Cytochrome P450 2C19 (CYP2C19), Cytochrome P450 2C9 (CYP2C9), and Cytochrome P450 2D6 (CYP2D6) as they play a major role in drug metabolism. The interindividual genetic variabilities of these enzymes can account for different responsiveness as well as concentration fluctuations for a particular drug.During the period of 2017 to 2018 a total of 54 patients have received pharmacogenetic testing at the Department of Genetics and Molecular Medicine at Kaunas Clinics. According to the genotype-metabolic phenotypes of CYP2C19, CYP2D6, CYP2C9 enzymes patients were classified according to the guidelines by Clinical Pharmacogenetics Implementation Consortium (CPIC): normal metabolizers (NMs), intermediate metabolizers (IMs), rapid metabolizers (RMs), ultrarapid metabolizers (UMs), and poor metabolizers (PMs).CYP2C19 enzyme allelic distribution: 18 patients (33.33%) with ∗1/∗1 genotype were NMs; 14 patients (25.93%) with ∗1/∗2; ∗2/∗17 genotypes were classified as IMs; 15 patients (27.78%) possessed ∗1/∗17 genotype and were RMs; 4 patients (7.4%) had ∗17/∗17 genotype with increased enzyme activity compared with RMs, were classified as UMs; 3 patients (5.56%) had ∗2/∗2 genotype and were marked as PMs. CYP2D6 enzyme allelic distribution: 26 patients (48.148%) contained ∗1/∗1,∗2/∗2,∗1/∗2,∗1/∗41,∗2/∗41 genotypes with normal enzymatic function so were accounted as NMs; 21 patients (38.89%) with ∗1/∗5, ∗2/∗4, ∗10/∗41, ∗1/∗4, ∗1/∗3, ∗2/∗5, ∗2/∗4, ∗2/∗6 genotypes were accounted as IMs; 2 patients (3.7%) possessed ∗2XN genotype and were accounted as UMs and 5 patients (9.26%) possessed ∗4/∗5,∗4/∗10,∗4/∗9,∗4/∗41 genotypes and had non-functional enzymatic activity so were accounted as PMs; CYP2C9 enzyme allelic distribution: 44 patients (81.48%) with∗1/∗1 genotype were NMs; 10 patients (18.52%) with ∗1/∗2;∗1/∗3 genotypes were IMs.The results of our study indicate that deviations from the normal enzymatic activity is common amongst Lithuanian people and combinatory genotyping of CYP2D6, CYP2C9, and CYP2C19 has to be promoted as an advanced method because of most commonly prescribed medicines like analgesics, antihypertensive, antidepressants are metabolized by multiple pathways involving enzymes in the CYP450 family.     

拷贝数变异测序在染色体易位夫妇植入前遗传学诊断中的临床应用

目的探讨拷贝数变异测序(copy number variation sequencing, CNV-seq)用于染色体易位夫妇胚胎植入前诊断的应用价值。 方法回顾性分析2017年1月至2018年12月，在广东省妇幼保健院生殖健康与不孕症科进行植入前遗传学诊断(preimplantation genetic diagnosis，PGD)的211对染色体易位夫妇患者的临床病例。使用CNV-seq对胚胎染色体进行检测，并对患者一般信息和PGD结果进行分析。 结果1210个胚胎中，被检出837个(79.2%)胚胎存在染色体异常，373个(30.8%)胚胎为整倍体。在241个PGD周期中，68个(27.6%)周期所有胚胎均存在染色体异常，178个(72.4%)周期至少含有一个整倍体胚胎。在176个移植周期中，130个(73.9%)确定临床妊娠，已出生46个健康婴儿，12例发生早期流产。 结论CNV-seq可准确地区分胚胎染色体是否存在异常，避免因胚胎含有染色体异常而被移植，是一种可靠而准确的PGD技术。     

Next-generation Sequencing for ALK and ROS1 Rearrangement Detection in Patients With Non–small-cell Lung Cancer: Implications of FISH-positive Patterns

BackgroundDetection of ALK and ROS1 gene rearrangements in non–small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation.Patients and MethodsForty non–small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated.ResultsNGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026).ConclusionOur data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications.     

Patterns of intervention utilization among school-aged children on the autism spectrum: Findings from a multi-site research consortium

When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as “evidence-based practice” or “other interventions,” reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0–79.3 h/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。