Pilot study of the impact that bilateral sacroiliac joint manipulation using a drop table technique has on gait parameters in asymptomatic individuals with a leg length inequality.

Purpose:

The purpose of this study was to pilot test our study procedures and estimate parameters for sample size calculations for a randomized controlled trial to determine if bilateral sacroiliac (SI) joint manipulation affects specific gait parameters in asymptomatic individuals with a leg length inequality (LLI).

Methods:

Twenty-one asymptomatic chiropractic students engaged in a baseline 90-second walking kinematic analysis using infrared Vicon® cameras. Following this, participants underwent a functional LLI test. Upon examination participants were classified as: left short leg, right short leg, or no short leg. Half of the participants in each short leg group were then randomized to receive bilateral corrective SI joint chiropractic manipulative therapy (CMT). All participants then underwent another 90-second gait analysis. Pre- versus post-intervention gait data were then analyzed within treatment groups by an individual who was blinded to participant group status. For the primary analysis, all p-values were corrected for multiple comparisons using the Bonferroni method.

Results:

Within groups, no differences in measured gait parameters were statistically significant after correcting for multiple comparisons.

Conclusions:

The protocol of this study was acceptable to all subjects who were invited to participate. No participants refused randomization. Based on the data collected, we estimated that a larger main study would require 34 participants in each comparison group to detect a moderate effect size.     

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization

Physical inactivity is a major health risk worldwide. Observational studies suggest that higher education is positively related to physical activity, but it is not clear whether this relationship constitutes a causal effect. Using participants (N = 1651) drawn from the Cardiovascular Risk in Young Finns Study linked to nationwide administrative data from Statistics Finland, this study examined whether educational attainment, measured by years of education, is related to adulthood physical activity in terms of overall physical activity, weekly hours of intensive activity, total steps per day, and aerobic steps per day. We employed ordinary least squares (OLS) models and extended the analysis using an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. Based on the MR results, it was found that years of education is positively related to physical activity. On average, one additional year of education leads to a 0.62-unit higher overall physical activity (P < .01), 0.26 more hours of weekly intensive activity (P < .05), 560 more steps per day (P < .10), and 390 more aerobic steps per day (P < .09). The findings indicate that education may be a factor leading to higher leisure-time physical activity and thus promoting global health.     

Where are clinical trials going? Society and clinical trials

Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information. Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator-led spin-off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor.     

基于评判视角研读随机对照试验研究文献

目前护理随机对照试验（RCT）研究文献发表数量逐年上升,其研究结果对护士和护生的临床知识、护理行为以及开展科研均会产生潜在影响,采取评判的态度和系统的方法正确阐释RCT研究结果,是将研究结果转化为临床实践的关键一步。因此本文基于此理念,从以下3个方面来评价一项RCT研究的结果及临床意义：1可信度：学会判断RCT研究结果的信度和效度;2结果的阐释：学会从样本量和精度看临床统计结果 ;3适用性：学会研读外在效度和干预措施的副作用,判断新方法的适用对象。从而促进研究成果的临床转化,提升我国护理质量。     

IMI Risk Factors for Myopia

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia.     

热敏灸社区实效性随机对照试验技术推荐(一):考虑患者偏好的随机化

热敏灸因"简单易学、操作简单、疗效明确"的特点,成为适合在社区广泛普及的中医外治法适宜技术。实效性随机对照试验是真实世界研究中的主要干预性研究方法,可为热敏灸社区管理效果评价提供高级别证据。本文聚焦区组随机、分层随机、整群随机、样本量分配、分配隐藏和盲法等随机化过程的关键环节,阐述了两阶段患者偏好随机法应用于热敏灸社区实效性随机对照试验的优缺点和技术细节,有利于提高研究的证据质量、可重复性和不同研究间的方法学同质性。     

Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?

Intellectual disability is common. Aristaless-related homeobox (ARX) gene is one of the most frequently mutated and pleiotropic genes, implicated in 10 different phenotypes. More than half of ∼100 reported cases with ARX mutations are due to a recurrent duplication of 24 bp, c.429_452dup, which leads to polyalanine tract expansion. The excess of affected males among the offspring of the obligate carrier females raised the possibility of transmission ratio distortion for the c.429_452dup mutation. We found a significant deviation from the expected Mendelian 1:1 ratio of transmission in favour of the c.429_452dup ARX mutation. We hypothesise that the preferential transmission of the c.429_452dup mutation may be due to asymmetry of meiosis in the oocyte. Our findings may have implications for genetic counselling of families segregating the c.429_452dup mutation and allude to putative role of ARX in oocyte biology.     

Meta-analysis of genetic studies using Mendelian randomization--a multivariate approach

In traditional epidemiological studies the association between phenotype (risk factor) and disease is often biased by confounding and reverse causation. As a person's genotype is assigned by a seemingly random process, genes are potentially useful instrumental variables for adjusting for such bias. This type of adjustment combines information on the genotype-disease association and the genotype-phenotype association to estimate the phenotype-disease association and has become known as Mendelian randomization. The information on genotype-disease and genotype-phenotype may well come from a meta-analysis. In such a synthesis, a multivariate approach needs to be used whenever some studies provide evidence on both the genotype-phenotype and genotype-disease associations. This paper presents two multivariate meta-analytical models, which differ in their treatment of the heterogeneities (between-study variances). Heterogeneities on the genotype-phenotype and genotype-disease associations may be highly correlated, but a multivariate model that parameterizes the heterogeneity directly is difficult to fit because that correlation is poorly estimated. We advocate an alternative model that treats the heterogeneities on genotype-phenotype and phenotype-disease as being independent. This model fits readily and implicitly defines the correlation between the heterogeneities on genotype-phenotype and genotype-disease. We show how either maximum likelihood or a Bayesian approach with vague prior distributions can be used to fit the alternative model.     

Teaching molecular genetics: chapter 4—positional cloning of genetic disorders

Positional cloning is the approach of choice for the identification of genetic mutations underlying the pathological development of diseases with simple Mendelian inheritance. It consists of different consecutive steps, starting with recruitment of patients and DNA collection, that are critical to the overall process. A genetic analysis of the enrolled patients and their families is performed, based on genetic recombination frequencies generated by meiotic cross-overs and on genome-wide molecular studies, to define a critical DNA region of interest. This analysis culminates in a statistical estimate of the probability that disease features may segregate in the families independently or in association with specific molecular markers located in known regions. In this latter case, a marker can be defined as being linked to the disease manifestations. The genetic markers define an interval that is a function of their recombination frequencies with the disease, in which the disease gene is localised. The identification and characterisation of chromosome abnormalities as translocations, deletions and duplications by classical cytogenetic methods or by the newly developed microarray-based comparative genomic hybridisation (array CGH) technique may define extensions and borders of the genomic regions involved. The step following the definition of a critical genomic region is the identification of candidate genes that is based on the analysis of available databases from genome browsers. Positional cloning culminates in the identification of the causative gene mutation, and the definition of its functional role in the pathogenesis of the disorder, by the use of cell-based or animal-based experiments. More often, positional cloning ends with the generation of mice with homologous mutations reproducing the human clinical phenotype. Altogether, positional cloning has represented a fundamental step in the research on genetic renal disorders, leading to the definition of several disease mechanisms and allowing a proper diagnostic approach to many conditions.