Evidence synthesis from aggregate recurrent event data for clinical trial design and analysis

Information from historical trials is important for the design, interim monitoring, analysis, and interpretation of clinical trials. Meta‐analytic models can be used to synthesize the evidence from historical data, which are often only available in aggregate form. We consider evidence synthesis methods for trials with recurrent event endpoints, which are common in many therapeutic areas. Such endpoints are typically analyzed by negative binomial regression. However, the individual patient data necessary to fit such a model are usually unavailable for historical trials reported in the medical literature. We describe approaches for back‐calculating model parameter estimates and their standard errors from available summary statistics with various techniques, including approximate Bayesian computation. We propose to use a quadratic approximation to the log‐likelihood for each historical trial based on 2 independent terms for the log mean rate and the log of the dispersion parameter. A Bayesian hierarchical meta‐analysis model then provides the posterior predictive distribution for these parameters. Simulations show this approach with back‐calculated parameter estimates results in very similar inference as using parameter estimates from individual patient data as an input. We illustrate how to design and analyze a new randomized placebo‐controlled exacerbation trial in severe eosinophilic asthma using data from 11 historical trials.     

基于SEER数据库的结直肠癌预后因素探讨及预后模型构建

分别使用logistic逐步回归法、贝叶斯模型平均法和LASSO回归进行特征变量筛选,分析美国SEER数据库的预后数据,探讨影响结直肠癌预后的相关因素,并应用人工神经网络分类算法构建预后模型,指导结直肠癌预后评价。结果证明,贝叶斯模型平均法结合人工神经网络的混合算法所构建的预后模型准确率最高。     

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma

Background:

Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC).

Methods:

Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months.

Results:

Median pretherapeutic serum GGT level was 25 U l⁻¹. Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l⁻¹ was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l⁻¹), normal high (17.5 to <34.5 U l⁻¹), elevated (34.5 to <181.5 U l⁻¹), and highly elevated (⩾181.5 U l⁻¹). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit.

Conclusions:

Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.     

The balance between Bayesian inference and default mode determines the generation of tinnitus from decreased auditory input: A volume entropy‐based study

Along with phantom pain, tinnitus, a phantom auditory perception occurring in the absence of an external acoustic stimulus, is one of the most representative phantom perceptions that develops in subjects with decreased peripheral sensory input. Although tinnitus is closely associated with peripheral hearing loss (HL), it remains unclear why only some individuals with HL develop tinnitus. In this study, we investigated the differences between 65 HL with tinnitus (HL‐T) and 104 HL with no tinnitus (HL‐NT) using a resting‐state electroencephalography data‐based volume entropy model of the brain network, by comparing the afferent node capacities, that quantify the contribution of each node to the spread of information, of all Brodmann areas. While the HL‐T group showed increased information flow in areas involved in Bayesian inference (the left orbitofrontal cortex, the left subgenual anterior cingulate cortex, and the left ventrolateral prefrontal cortex) and auditory memory storage (the right hippocampus/parahippocampus), the HL‐NT group showed increased afferent node capacity in hub areas of the default mode network (DMN; the right posterior cingulate cortex and the right medial temporal gyrus). These results suggest that the balance of activity between the Bayesian inferential network (updating missing auditory information by retrieving auditory memories from the hippocampus/parahippocampus) and DMN (maintaining the “silent status quo”) determines whether phantom auditory perception occurs in a brain with decreased peripheral auditory input.     

Cortical current source estimation from electroencephalography in combination with near-infrared spectroscopy as a hierarchical prior

Previous simulation and experimental studies have demonstrated that the application of Variational Bayesian Multimodal EncephaloGraphy (VBMEG) to magnetoencephalography (MEG) data can be used to estimate cortical currents with high spatio-temporal resolution, by incorporating functional magnetic resonance imaging (fMRI) activity as a hierarchical prior. However, the use of combined MEG and fMRI is restricted by the high costs involved, a lack of portability and high sensitivity to body-motion artifacts. One possible solution for overcoming these limitations is to use a combination of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). This study therefore aimed to extend the possible applications of VBMEG to include EEG data with NIRS activity as a hierarchical prior. Using computer simulations and real experimental data, we evaluated the performance of VBMEG applied to EEG data under different conditions, including different numbers of EEG sensors and different prior information. The results suggest that VBMEG with NIRS prior performs well, even with as few as 19 EEG sensors. These findings indicate the potential value of clinically applying VBMEG using a combination of EEG and NIRS.     

The Factors Affecting the Development of National Identity as South Korean in North Korean Refugees Living in South Korea

Objective

This study aims to observe the factors that influence the development of national identity of North Korean refugees who have resettled in South Korea.

Methods

The study population was comprised of 500 North Korean refugees who immigrated to South Korea in 2007. The variables measured national identity as South Korean, a scale for discrimination perceived during daily life, a social for supporting social network, a for childhood trauma experience, traumatic experiences in North Korea, and traumatic experiences during the escape process. Factor analysis was conducted on the result from the scale for national identity as South Korean which produced 4 factors including national consciousness, positive emotions, positive values, and negative values. Multiple regression was done to identify how variables such as demographic data, discrimination, social network, and past trauma had influenced each of 4 factors.

Results

National identity was negatively related by traumatic experience during childhood, perceived discrimination, and positively influenced by social networks. Positive emotion was related negatively to education level in North Korea and perceived discrimination, but positively related to traumatic experiences in North Korea. Negative value was related positively age and perceived discrimination but negatively related to supporting social network.

Conclusion

The results of this study suggests that promoting social networks, decreasing discrimination and healing past traumas were important factors for North Korean refugees in South Korea to facilitate a new national identity as a South Korean.     

Bayesian spatiotemporal model of fMRI data

This research describes a new Bayesian spatiotemporal model to analyse block-design BOLD fMRI studies. In the temporal dimension, we parameterise the hemodynamic response function's (HRF) shape with a potential increase of signal and a subsequent exponential decay. In the spatial dimension, we use Gaussian Markov random fields (GMRF) priors on activation characteristics parameters (location and magnitude) that embody our prior knowledge that evoked responses are spatially contiguous and locally homogeneous. The result is a spatiotemporal model with a small number of parameters, all of them interpretable. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on real data from a block-design fMRI experiment.     

Practitioner attitudes towards patients in forensic mental health settings

Scotland has a national programme to improve mental health and well-being and addressing stigma among mental health practitioners is a priority. This study explores practitioner attitudes towards patients in medium and low secure forensic mental health settings through qualitative and quantitative approaches. Two questionnaires were used with nursing staff. A qualitative questionnaire asked participants to list examples of positive and negative practice and anti-discriminatory and discriminatory attitudes towards patients within forensic services. A quantitative questionnaire then asked participants to answer questions about a hypothetical man with schizophrenia called Harry. The overall balance of responses was more positive than negative in the qualitative results, particularly regarding patient rights, empowerment and control. However, there were a significant minority of negative attitudes in relation to recovery pessimism and desire for social distance. This was supported by the quantitative results where practitioners showed high stigma scores for avoidance and segregation. There were no significant differences in attitudes between medium and low secure settings. However overall, males reported more negative attitudes in relation to blame and avoidance and younger participants demonstrated more negative attitudes than older participants in relation to fear and danger. The implications for addressing stigma are discussed in relation to the wider national anti-stigma campaign and forensic services specifically.     

Obstetric Violence as Reproductive Governance in the Dominican Republic

ABSTRACT

A human rights violation, obstetric violence encompasses numerous forms of mistreatment against women giving birth in health care facilities. Based on this framework, we conducted open-ended exit interviews with 43 women who had given birth at either one of the two largest public maternity hospitals in the Dominican Republic. Women’s narratives revealed a contrast between scholarly definitions of obstetric violence and their own perceptions of receiving abusive care. Analyzing obstetric violence as a form of reproductive governance and the adaptive preference that ensues helps explain why most women accepted with endurance the poor quality of care that they received.