Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10^-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10^-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10^-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.     

基于医院信息系统的乳腺癌临床特征及中西医用药特征分析

目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征，为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统（Hospital Information System，HIS）中，出院诊断为“乳腺癌”的患者用药信息，采用SAS9.3统计软件，对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者，平均年龄（50.93者，平均年龄）岁；多以门诊入院，入院病情以“一般”为主;合并疾病主要为高血压，骨肿瘤，联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主；中医辨证以痰瘀互结证，气阴两虚证，肝气淤滞证，脾气亏虚证型最为常见，临床清热解毒剂、益气扶正剂，活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗，联用药物广泛，临床治疗基本符合临床指南。     

Association of weight-adjusted-waist index with incident hypertension: The Rural Chinese Cohort Study

AimsTo explore the association between WWI and the incidence of HTN in the Rural Chinese Cohort Study.Methods and ResultsWe examined data for 10,338 non-hypertensive participants (39.49% men) aged ≥ 18 years from the Rural Chinese Cohort Study who completed a baseline examination during 2007–2008 and follow-up during 2013–2014. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of HTN across four WWI categories. Restricted cubic splines analysis was used to model the dose–response association of WWI and HTN. A total of 2078 participants had HTN during a median follow-up of 6 years. After adjusting for potential confounders, as compared with the lowest WWI category (<9.94 cm/√kg), with WWI 9.94 to 10.42, 10.42 to 10.91 and ≥ 10.91 cm/√kg, the ORs (95% CIs) for HTN were 1.12 (0.93–1.35), 1.40 (1.17–1.69) and 1.50 (1.24–1.82), respectively. Results of the sensitivity analyses were robust. The ORs were generally consistent on subgroup analysis by sex, smoking status, systolic blood pressure and diastolic blood pressure. Multiple logistic regression models with restricted cubic splines showed a non-linear positive association between WWI and HTN (P_nonlinearity < 0.001).ConclusionThe highest WWI category was significantly associated with increased risk of HTN. Our findings may facilitate the development and promotion of obesity prevention strategies aimed at reducing the risk of HTN and provide evidence for healthcare policy in rural China.     

Attending Physicians' Perspectives of Resident Academic Half Day

Phenomenon: Academic health centers face significant challenges trying to improve medical education while meeting patient care needs. In response to problems with traditional forms of didactic education, many residency programs have transitioned to Academic Half Day (AHD), a curricular model in which learning is condensed into half-day blocks. In this model, trainees have protected educational time free from clinical responsibilities. However, an understanding of the impact on attending physicians and patient care when residents depart clinical sites for learning activities has not been well described. We sought to explore attending physicians’ perspectives when residents depart clinical sites to attend AHD. Approach: We performed a qualitative study with a grounded theory approach using individual semistructured interviews (December 2016–April 2017) of attending physicians who worked at inpatient and emergency department clinical sites from which residents departed to attend AHD. We used the constant comparative method, generating codes using an iterative approach and continuing sampling until saturation was reached. Major themes were identified and disagreements were resolved by consensus. Findings: Fifteen attending physicians from 6 clinical services were interviewed. Data analysis yielded 5 themes: emotional strain of workload, technology and systems challenges, patient safety and care concerns, disrupted resident learning, and the challenge to optimize resident education. Attending physicians, already working on busy services, felt frustrated and perceived having an increased workload when residents departed for AHD. They were concerned about safely entering orders in the electronic health record, impeded patient workflow, and further disruption of resident schedules already disrupted by duty hour restrictions and continuity clinic. Attending physicians described the importance of experiential learning from caring for patients and from structured didactic learning; however, the optimal balance was uncertain. Insights: We found that attending physicians experienced significant emotional strain, faced technological challenges, and were concerned about impeded workflow and patient safety when residents departed clinical sites for AHD. This is likely to be true whenever residents are pulled out of the clinical setting for any reason. Educators need to partner with hospital administrators to provide appropriate support for attending physicians when residents leave clinical sites, evaluate the effectiveness of different educational models, and determine how structured learning activities fit into the overall curriculum.     

Association of genetic variants at MYP10 and MYP15 with high myopia in a Han Chinese population

Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.

Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).

Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify.