Fallback tests for co‐primary endpoints

When efficacy of a treatment is measured by co‐primary endpoints, efficacy is claimed only if for each endpoint an individual statistical test is significant at level α. While such a strategy controls the family‐wise type I error rate (FWER), it is often strictly conservative and allows for no inference if not all null hypotheses can be rejected. In this paper, we investigate fallback tests, which are defined as uniform improvements of the classical test for co‐primary endpoints. They reject whenever the classical test rejects but allow for inference also in settings where only a subset of endpoints show a significant effect. Similarly to the fallback tests for hierarchical testing procedures, these fallback tests for co‐primary endpoints allow one to continue testing even if the primary objective of the trial was not met. We propose examples of fallback tests for two and three co‐primary endpoints that control the FWER in the strong sense under the assumption of multivariate normal test statistics with arbitrary correlation matrix and investigate their power in a simulation study. The fallback procedures for co‐primary endpoints are illustrated with a clinical trial in a rare disease and a diagnostic trial. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.     

In vitro effect of 4-pentylphenol and 3-methyl-4-nitrophenol on murine splenic lymphocyte populations and cytokine/granzyme production

Gasoline exhaust particles (GEP) and diesel exhaust particles (DEP) are considered to be some of the most important air pollutants. Among the many constituents in these pollutant particles, 4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC) are considered important phenolics in GEP and DEP, respectively. The aim of this study was to investigate the effect of in vitro exposure to commercially-supplied PP and PNMC on populations of, and production of interleukin (IL)-2, IL-4 and granzyme-B by, mouse splenic lymphocytes. After in vitro exposure to PP or PNMC for 48 h, splenocyte viability was measured, cell phenotypes, e.g. B-cell (CD19), T-cells (CD3), T-cell subsets (CD4 and CD8), were quantified by flow cytometry and production of IL-2, IL-4 and granzyme-B was assessed via ELISA. The oxidative toxicity of PP and PNMC toward the splenocytes was also evaluated using measures of hydroxyl radical and malondiadehyde production and changes in glutathione peroxidase and superoxide dismutase activities. Results showed that in vitro exposure to PP and PNMC inhibited splenic cell parameters in a dose-related manner. Exposure to PP and PNMC decreased splenic T-lymphocyte populations and splenocyte production of cytokines and granzyme B, as well as induced oxidative stress in the splenocytes. The results also showed that the percentages of CD3⁺ T-cells overall and of CD4⁺ and CD8⁺ T-cells therein, among exposed splenocytes, were reduced; neither compound appeared to affect levels of CD19⁺ B-cells. Overall, the suppressive effects of PP were stronger than PNMC. The data here provide support for the proposal that PP-/PNMC-induced toxicity in splenocytes may be due at least in part to oxidative damage and that PP and PNMC – as components of GEP and DEP – might significantly impact on splenic T-cell formation/release of cytokines/granzymes in situ.     

Activities of daily living and chewing ability in an 80-year-old population

OBJECTIVES: The aim of this study was to determine whether chewing ability or number of intact teeth was related to performance of activities of daily living in 80-year olds. DESIGN: This was a cross-sectional survey including dental examinations, chewing self-assessment, and everyday function. SUBJECTS AND METHODS: A total of 823 people (309 males, 514 females) who were 80 years of age and resident in the Fukuoka Prefecture, Japan participated in this study. RESULTS: The mean number of intact teeth was 7.5 +/- 8.7; of the 15 food items offered, the mean number of foods chewed was 11.2 +/- 3.8. Function was independent in 713 subjects, and dependent in 93. After adjustment for gender, we found the number of foods chewed being linked to independent function by the multiple regression analysis (beta = 0.223, P < 0.0001); the number of intact teeth was only weakly related (beta = 0.077, P = 0.03). By logistic regression analysis, functional dependency was 7.5 times more prevalent in individuals capable of chewing four foods or fewer, and 3.3 times more prevalent in those chewing five to nine, than in those chewing all 15 items. No significant functional difference was related to the number of intact teeth. CONCLUSION: Chewing ability may be independently related with functional status in 80-year olds.     

基于ISSR技术和非腺毛特征研究柔毛淫羊藿和近缘种遗传关系和居群遗传多样性

该研究对柔毛淫羊藿14个居群和星花淫羊藿1个居群共128个单株进行ISSR分析,用POPGENE计算相关系数,UPGMA进行聚类分析,以及用光学显微镜观察了每个居群叶背主要非腺毛类型和特点。研究发现:非腺毛可分为5个形态类别,分别为长直毛、长卷曲毛、伏卷曲毛、拟短伏毛和长伏毛;筛选出的8个ISSR引物共扩增出94个条带,其中多态性条带90个,基于ISSR聚类分析结果,15个居群分为3个分支,星花淫羊藿居群并没有单独为一支,应不能独立成种,应并入柔毛淫羊藿或者作为柔毛淫羊藿的种下等级;柔毛淫羊藿居群间遗传关系与地理分布及非腺毛特征具有良好的相关性,但也存在不一致的情况,这对于进一步研究柔毛淫羊藿以及淫羊藿属植物的种间关系和成种方式提供了良好的提示。居群多样性分析表明柔毛淫羊藿居群的基因流N_m为0.354 4,Nei's基因分化系数为0.585 2,说明居群间表现出较高水平的遗传分化,主要原因可能来自柔毛淫羊藿居群自交率高和种子散布范围小。     

漂浮体位治疗踝关节复杂骨折的临床效果分析

目的:探讨三踝骨折在漂浮体位下行手术治疗的临床效果及优势.方法:回顾性分析2011年1月至2014年1月收治的三踝骨折患者122例,随机分为A组(漂浮体位)63例,B组(常规仰卧位)59例,A组采用漂浮体位下行切开复位内固定术,B组采用常规卧位行切开复位内固定术,固定顺序均为外踝、后踝、内踝;术后早期功能锻炼,6～8周开始部分负重.结果:A组61例获得随访,B组58例获得随访,随访时间5～36个月,平均14个月,A组手术时间小于B组(P＜0.05),按美国足踝外科协会踝-后足评分系统评定标准评定,A组优良率明显高于B组(P＜0.05).结论:踝关节复杂骨折采用漂浮体位行切开复位内固定术所用手术时间及术后优良率明显优于常规卧位,术后踝关节功能可达到满意效果.     

HLA-E coding and 3′ untranslated region variability determined by next-generation sequencing in two West-African population samples

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5′UTR, introns and the 3′UTR) in two African population samples, Susu from Guinea–Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3′UTR is quite polymorphic and (d) haplotypes in the HLA-E 3′UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.     

Association and differences in genetic polymorphisms in PCSK9 gene in subjects with lacunar infarction in the Han and Uygur populations of Xinjiang Uygur Autonomous Region of China

Polymorphisms in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are associated with severe hypercholesterolemia and stroke. Here, we investigated the relationship between single nucleotide polymorphisms in PCSK9 and stroke in 237 patients with lacunar infarction in the Uygur and Han populations in Xinjiang Uygur Autonomous Region of China. Using the SNaPshot single-base termi-nal extension method, four PCSK9 gene polymorphisms were analyzed. We found a significantly strong relationship between the PCSK9 rs17111503 (G > A) polymorphism and increased susceptibility to lacunar infarction by variant homozygote comparison, and using the dominant and recessive models in the Han population but not in the Uygur population. Low triglyceride levels were found in AA carriers (rs17111503, G > A) in the Han population but not in the Uygur population. Association analysis revealed that the rs17111503 (G > A) polymorphism was not significantly associated with smoking, alcohol drinking, history of hypertension or diabetes in the Han or Uygur lacunar infarction patients. rs11583680, rs483462 and rs505151 were not associated with risk of lacunar infarction in the Han or Uygur populations. Our findings suggest that the PCSK9 rs17111503 (G > A) polymorphism is associated with susceptibility to lacunar infarction in the Han population but not in the Uygur population.     

The Floating Knee Injuries: Does it Need a New Classification System?

BackgroundThis study aims to determine the differences between the clinical and radiological results of patients based on Karlstrom–Olerud Scoring System who cannot be included in any classification for floating knee injuries and to seek an answer to the question of whether a new classification is needed.Material and MethodsSeventy patients with floating knee injuries treated in our clinic were retrospectively analyzed between 2008 and 2019 in the study. The results of fractures that classifiable and unclassifiable according to the Fraser, Blake and McBryde classifications were statistically compared based on the Karlstrom–Olerud criteria.ResultsSeventy patients, 64 males and 6 females, participated in the study. The mean age of our patients was 32.3 ± 12.55 (18–68) years. The mean follow-up period of the patients was 30.26 ± 18.19 months (11–60 months). The results of the fractures that could not be classified according to the Blake and McBryde classification were statistically poorer than the results of those that could be classified according to the criteria (p = 0.041).The results of the fractures that could not be classified according to the Fraser classification were statistically poorer than the results of those that could be classified according to the criteria defined by Karlstrom and Olerud (p = 0.010).ConclusionWe observed that floating knee injuries that we could and could not classify led to different clinical results. In conclusion, we think that there is a need for a new floating knee classification that includes segmental fractures, patellar fractures and open fractures.     

Benefit–risk evaluation of COVID-19 vaccination in special population groups of interest

Several population groups display an increased risk of severe disease and mortality following SARS-CoV-2 infection. These include those who are immunocompromised (IC), have a cancer diagnosis, human immunodeficiency virus (HIV) infection or chronic inflammatory disease including autoimmune disease, primary immunodeficiencies, and those with kidney or liver disease. As such, improved understanding of the course of COVID-19 disease, as well as the efficacy, safety, and benefit-risk profiles of COVID-19 vaccines in these vulnerable groups is paramount in order to inform health policy makers and identify evidence-based vaccination strategies. In this review, we seek to summarize current data, including recommendations by national health authorities, on the impact and benefit-risk profiles of COVID-19 vaccination in these populations. Moving forward, although significant efforts have been made to elucidate and characterize COVID-19 disease course and vaccine responses in these groups, further larger-scale and longer-term evaluation will be instrumental to help further guide management and vaccination strategies, particularly given concerns about waning of vaccine-induced immunity and the recent surge of transmission with SARS-CoV-2 variants of concern.     

Food insecurity and dental caries in schoolchildren: a cross‐sectional survey in the western Brazilian Amazon

We analyzed the association between food insecurity and dental caries in 7‐ to 9‐yr‐old schoolchildren. We performed a cross‐sectional survey nested in a population‐based cohort study of 203 schoolchildren. The participants lived in the urban area of a small town within the western Brazilian Amazon. Dental examinations were performed according to criteria recommended by the World Health Organization. The number of decayed deciduous and permanent teeth as a count variable was the outcome measure. Socio–economic status, food security, behavioral variables, and child nutritional status, measured by Z‐score for body mass index (BMI), were investigated, and robust Poisson regression models were used. The results showed a mean (SD) of 3.63 (3.26) teeth affected by untreated caries. Approximately 80% of schoolchildren had at least one untreated decayed tooth, and nearly 60% lived in food‐insecure households. Sex, household wealth index, mother's education level, and food‐insecurity scores were associated with dental caries in the crude analysis. Dental caries was 1.5 times more likely to be associated with high food‐insecurity scores after adjusting for socio–economic status and sex. A significant dose–response relationship was observed. In conclusion, food insecurity is highly associated with dental caries in 7‐ to 9‐yr‐old children and may be seen as a risk factor. These findings suggest that food‐security policies could reduce dental caries.