Pediatric Lipid Screening and Treatment in Canada: Practices,Attitudes, and Barriers

The pediatric lipid screening and treatment practices, attitudes, and perceived barriers of Canadian pediatricians are not known. We sought to evaluate this in a survey of pediatricians through the Canadian Pediatric Surveillance Program (CPSP) in March 2019. The survey included an assessment of lipid screening of 9- to 11-year-old youth and a hypothetical case of persistent severe dyslipidemia to ascertain management practices. There were 759 respondents (28% response rate, 759 of 2742), of whom 236 provided outpatient primary care to 9- to 11-year-old youth as part of their routine clinical practice. Among primary care-providing pediatricians, universal lipid screening of healthy 9- to 11-year-old youth most or all of the time was reported by 3% (8 of 230). Reported screening practices most or all of the time were more common for youth with risk factors such as overweight and obesity (54%, 127 of 235) and a family history of premature cardiovascular disease (39%, 85 of 217). Most respondents would refer a child with severe persistent dyslipidemia to dieticians (69%, 152 of 220) and a lipid specialist (64%, 144 of 220) most or all of the time, whereas 7% (16 of 220) would start statin therapy themselves. A lack of Canadian pediatric lipid guidelines was reported as a major barrier for 49% (114 of 233) and minor barrier for 40% (93 of 213). The rate of routine lipid screening of healthy 9- to 11-year-old youth among Canadian primary care-providing pediatricians is low and at odds with current US guidelines. This discrepancy may be due at least in part to a lack of Canadian guidelines on pediatric dyslipidemia, the development of which may address certain perceived barriers and influence future attitudes.     

Epidemiology of maternal morbidity and mortality

Maternal morbidity and mortality remains a significant health care concern in the United States, as the rates continue to rise despite efforts to improve maternal health. In 2013, the United States ranked 60th in maternal mortality worldwide. We review the definitions, rates, trends, and top causes of severe maternal morbidity and mortality, as well as risk factors for adverse maternal outcomes. We describe current local and national initiatives in place to reduce maternal morbidity and mortality and offer suggestions for future research.     

父母饮酒与儿童青少年饮酒的关联分析

目的 探讨父母饮酒与儿童青少年饮酒的关系,为儿童青少年饮酒的防控政策制定提供科学依据。方法 采用方便整群抽样的方法,选取济南市城区8~17岁儿童青少年,通过调查问卷获取儿童青少年及其父母饮酒的相关信息,共获得有效样本量2 785人。采用多因素logistic回归模型分析父母饮酒与儿童青少年饮酒的关系。结果 儿童青少年饮酒者占11.2%（311名）,父亲饮酒者占58.6%（1 633名）,母亲饮酒者占7.3%（204名）。与父亲从不饮酒者相比,父亲现在饮酒（OR=1.36,95% CI：1.03~1.80）和重度饮酒（OR=2.09,95% CI：1.44~3.05）与儿童青少年饮酒存在关联。与母亲从不饮酒者相比,母亲现在饮酒也与儿童青少年饮酒存在关联（OR=2.72,95% CI：1.89~3.91）。与父母均不饮酒者相比,父母仅一方饮酒（OR=1.58,95% CI：1.20~2.09）和父母双方均饮酒（OR=4.12,95% CI：2.73~6.20）与儿童青少年饮酒存在关联。按照性别、年龄组分层分析,男生组及13~17岁组的结果与总体结果类似,但是仅父亲重度饮酒或父母双方均饮酒与女生、8~12岁儿童饮酒存在关联。结论 父母饮酒可能是儿童青少年饮酒的重要影响因素。今后儿童青少年饮酒的防控政策制定应该考虑父母饮酒因素。     

1991—2015年中国9个省份儿童青少年超重和肥胖率的变化趋势分析

目的分析1991—2015年中国9个省份儿童青少年超重和肥胖率的变化趋势。方法采用1991—2015年9次“中国健康与营养调查”数据,选取资料完整的14888名6~17岁儿童青少年为研究对象。超重和肥胖分别采用2000年国际肥胖工作组(IOTF)制定的全球儿童超重和肥胖标准(IOTF标准)、2007年世界卫生组织(WHO)制定的学龄儿童青少年生长参照标准(WHO标准)、2009年李辉等制定的儿童超重肥胖筛查体重指数界值(专家标准)及2018年原国家卫生和计划生育委员会发布的学龄儿童青少年超重与肥胖筛查界值(行业标准)进行判定。采用多元线性回归模型分析1991—2015年儿童青少年体重指数变化趋势,采用logistics回归模型分析1991—2015年超重和肥胖率的变化趋势。结果调整年龄、性别和地区后,体重指数由1991年(2363名)的17.26 kg/m2上升至2015年(1060名)的18.72 kg/m2(P趋势<0.001)。根据IOTF标准、WHO标准、专家标准和行业标准,超重率分别由1991年的4.06%、5.37%、5.16%、4.27%增长至2015年的13.58%、16.23%、13.30%、11.70%(P趋势<0.001),肥胖率分别由1991年的1.02%、1.86%、2.24%、2.41%增长至2015年的7.45%、10.75%、12.08%、12.74%(P趋势<0.001)。结论1991—2015年,我国9个省份儿童青少年体重指数水平、超重和肥胖率均呈逐年增加趋势。     

儿童腹型肥胖及其肥胖类型与颈动脉内中膜厚度的关系

目的 探讨儿童腹型肥胖及其肥胖类型与颈动脉内中膜厚度（cIMT）的关系,为儿童心血管结构异常的防治提供科学依据。方法 数据来源于2017年11月至2018年1月在山东省淄博市桓台县开展的“儿童心血管健康队列”基线调查数据。本研究纳入性别、年龄、体测指标、血生化指标和问卷调查变量等信息完整的儿童1 240名（男生657人,占53.0%）。采用协方差分析比较正常腰围组、腹型肥胖前期组和腹型肥胖组儿童的cIMT水平,采用logistic回归模型分析腹型肥胖前期、腹型肥胖与cIMT增厚（以性别、年龄别的P₉₅为界值点）及外周型超重/肥胖与腹型肥胖或前期的联合作用与cIMT增厚的关系。结果 腹型肥胖前期组、腹型肥胖组cIMT水平高于正常腰围组（0.47±0.03、0.50±0.04 vs.0.45±0.05）mm,差异有统计学意义（P<0.001）。腹型肥胖前期组、腹型肥胖组cIMT增厚检出率高于正常腰围组（20.8%、49.5% vs.8.8%,P<0.001）。调整各种潜在协变量后,与正常腰围相比,腹型肥胖前期、腹型肥胖与cIMT增厚存在关联（腹型肥胖前期：OR=2.53,95% CI：1.67~3.84;腹型肥胖：OR=8.56,95% CI：5.97~12.29）。与BMI和腰围均正常者相比,仅腹型肥胖或前期和混合型超重/肥胖均与cIMT增厚存在关联（仅腹型肥胖或前期：OR=2.24,95% CI：1.36~3.69;混合型超重/肥胖：OR=6.94,95% CI：4.87~9.90）。结论 儿童腹型肥胖与cIMT增厚存在较强关联,混合型超重/肥胖与cIMT增厚的关联性更强。提示儿童心血管结构异常的防治,应当考虑混合型超重/肥胖的重要性。     

Preinvasive disease of the airway

Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those ‘at risk’ of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.     

Differential Roles of Life-Course Cumulative Burden of Cardiovascular Risk Factors in Arterial Stiffness and Thickness

BackgroundData are limited regarding differential and common effects of cardiovascular risk factors on subclinical changes in vascular structure and function. We aimed to examine the relationships of life-course cumulative burdens of cardiovascular risk factors with adult arterial pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) in a longitudinal cohort of the Bogalusa Heart Study.MethodsThe cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors.ResultsAdjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β] = 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β = 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β = 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β = 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups.ConclusionsThe life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life.     

Eltrombopag or Intravenous Immunoglobulin as a Bridge to Splenectomy in Adults With Chronic Idiopathic Thrombocytopenic Purpura: A Canadian Economic Analysis

BackgroundChronic idiopathic thrombocytopenia purpura (ITP) in adults is a potentially serious disorder affecting 6000 to 7000 Canadians. Initial treatment consisting of corticosteroids usually begins when the platelet count is persistently below 20 × 10⁹/L or if the patient has bleeding complications. In cases in which corticosteroid resistance develops or in which they are contraindicated, splenectomy is the recommended second-line therapy. In many of these patients, intravenous immunoglobulin (IVIG; 1 g/kg/day for 2 days then 1 g/kg/day monthly) is often used as a bridge to surgery. Eltrombopag is a new orally administered agent that activates the thrombopoietic receptor and stimulates human megakaryocytes. Clinical trials have demonstrated that eltrombopag is safe and effective in the treatment of adults with chronic ITP. Therefore, it represents an attractive option to IVIG for use as a bridge to splenectomy. In this study, a cost-minimization analysis was conducted to test the hypothesis that eltrombopag is a cost-effective alternative to IVIG for this indication.Patients and MethodsThe economic analysis was conducted from the Canadian societal perspective using a 4-month time horizon. Estimates for direct medical costs in these patients were obtained from 6 hematologists from across Canada. The base case analysis considered direct costs for drug therapy, outpatient pharmacy fees, medical consultations and visits, laboratory and diagnostic procedures, as well as costs for secondary pharmacotherapy in cases in which the primary agent had to be discontinued because of side effects. For IVIG, the analysis also included visits to the infusion clinic, chair time to receive the infusion, nursing time, pharmacy preparation, as well as indirect costs (eg, time off work, patient travel). A 1-way sensitivity analysis was then undertaken on the key cost drivers to test the stability of the primary findings.ResultsTotal direct and indirect costs for IVIG were $24,134 for 4 months of therapy with drug cost contributing to 84% of the total. In contrast, total costs for eltrombopag were approximately $14,651 for an overall savings of $9,543 per patient. The sensitivity analysis suggested that the base case findings were stable and were only modestly affected by variations in drug cost and duration of therapy.ConclusionGiven its oral route of administration and cost-saving potential, eltrombopag would be an economically attractive alternative to IVIG when the intent of therapy is to create a bridge to surgery.     

De novo missense variants in the E3 ubiquitin ligase adaptor KLHL20 cause a developmental disorder with intellectual disability,epilepsy, and autism spectrum disorder

PurposeKLHL20 is part of a CUL3-RING E3 ubiquitin ligase involved in protein ubiquitination. KLHL20 functions as the substrate adaptor that recognizes substrates and mediates the transfer of ubiquitin to the substrates. Although KLHL20 regulates neurite outgrowth and synaptic development in animal models, a role in human neurodevelopment has not yet been described. We report on a neurodevelopmental disorder caused by de novo missense variants in KLHL20.MethodsPatients were ascertained by the investigators through Matchmaker Exchange. Phenotyping of patients with de novo missense variants in KLHL20 was performed.ResultsWe studied 14 patients with de novo missense variants in KLHL20, delineating a genetic syndrome with patients having mild to severe intellectual disability, febrile seizures or epilepsy, autism spectrum disorder, hyperactivity, and subtle dysmorphic facial features. We observed a recurrent de novo missense variant in 11 patients (NM_014458.4:c.1069G>A p.[Gly357Arg]). The recurrent missense and the 3 other missense variants all clustered in the Kelch-type β-propeller domain of the KLHL20 protein, which shapes the substrate binding surface.ConclusionOur findings implicate KLHL20 in a neurodevelopmental disorder characterized by intellectual disability, febrile seizures or epilepsy, autism spectrum disorder, and hyperactivity.