Accuracy of Pulse Oximeters in Detecting Hypoxemia in Patients with Chronic Thromboembolic Pulmonary Hypertension

PurposePulse oximetry is routinely used to continuously and non-invasively monitor arterial oxygen saturation (SaO₂). When oxygen saturation by pulse oximeter (SpO₂) overestimates SaO₂, hypoxemia may be overlooked. We compared the SpO₂ - SaO₂ differences among three pulse oximeters in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who spent their daily lives in a poor oxygen state.ResultThe root mean square of each pulse oximeter was 1.79 (OLV-3100), 1.64 (N-BS), and 2.50 (Masimo Radical). The mean bias (SpO₂ - SaO₂) for the 90%–95% saturation range was significantly higher for Masimo Radical (0.19 +/- 1.78% [OLV-3100], 0.18 +/- 1.63% [N-BS], and 1.61 +/- 1.91% [Masimo Radical]; p<0.0001). The optimal SpO₂ value to detect hypoxemia (SaO₂≦90%) was 89% for OLV-3100, 90% for N-BS, and 92% for Masimo Radical.ConclusionWe found that the biases and precision with which to detect hypoxemia differed among the three pulse oximeters. To avoid hypoxemia, the optimal SpO₂ should be determined for each pulse oximeter.     

Comparison of 3 Methods to Induce Acute Pulmonary Hypertension in Pigs

Large animal models for acute pulmonary hypertension (PHT) show distinct differences between species and underlying mechanisms. Two embolic procedures and continuous infusion of a stable thromboxane A₂ analogue (U46619) were explored for their ability to induce PHT and their effects on right ventricular function and pulmonary and systemic circulation in 9 pigs. Injection of small (100 to 200 µm) or large (355 to 425 µm) polystyrene beads and incremental dosage (0.2 to 0.8 µg kg⁻¹ min⁻¹) of U46619 all induced PHT. However, infusion of U46619 resulted in stable PHT, whereas that after bead injection demonstrated a gradual continuous decline in pressure. This instability was most pronounced with small beads, due to right ventricular failure and consecutive circulatory collapse. Furthermore, cardiac output decreased during U46619 infusion but increased after embolization with no relevant differences in systemic pressure. This result was likely due to the more pronounced effect of U46619 on pulmonary resistance and impedance in combination with limited effects on pulmonary gas exchange. Coronary autoregulation and adaption of contractility to afterload increase was not impaired by U46619. All parameters returned to baseline values after infusion was discontinued. Continuous infusion of a thromboxane A2 analogue is an excellent method for induction of stable, acute PHT in large animal hemodynamic studies.Abbreviations: PHT, pulmonary hypertensionSystematic investigation of the pathophysiology of acute pulmonary hypertension (PHT), especially adaption of the right ventricular function in response to increased afterload, requires valid animal models with conclusions that are transferable to humans. In addition, the availability of such models would promote the evaluation of treatment options for pulmonary vasodilatation and inotropic support of the right ventricle. The various models reported in the literature can be classified by animal size, developmental period, and techniques. Due to cardiac dimensions and basic regulatory principles, sophisticated and transferable hemodynamic measurements require large animals such as dogs, pigs, and goats, and differences in vasoconstrictory responsiveness and adaption to hypoxia between these species and humans must be taken into account.^9,16,21 Chronic models of PHT in large animals are used less frequently than acute models and typically are induced through injection of monocrotaline pyrrole,⁶ surgical creation of an aortopulmonary shunt,²² or pulmonary banding.⁵ Techniques for the induction of acute PHT can be weighed in light of their underlying mechanisms, side effects, stability, and reversibility. Exposure to hypoxia ⁶ and repeated embolism^{9,17, 23} are used more frequently than are constriction of the pulmonary artery or infusion of the stable thromboxane A₂ analogue U46619.⁵ Whereas hypoxia mediates vasoconstriction by means of endothelin 1, serotonin, and the inhibition of voltage-gated potassium channels in smooth muscle cells,⁷ embolic procedures reduce the vascular cross-sectional area and increase concentrations of thromboxane A2.¹⁹ The size of injected particles positively correlates with the degree of hypoxia⁹ and inversely correlates with induction of thromboxane A2 production, thereby resulting in PHT and circulatory collapse.¹⁹ These mechanisms influence the stability of PHT, cardiac function, and sympathetic tone as a consequence of hypoxia. A leading advantage of transient occlusion, constriction of the pulmonary artery, and infusion of U46619 is that the resulting PHT is reversible. Compared with embolic procedures, proximal occlusion of the pulmonary artery induced different grade of afterload increase for the right ventricle, whereas U46619 may have systemic and coronary vasoconstrictory effects, thus causing negative inotropy.¹¹ The design of a study involving a PHT model therefore is influenced not only by the animal and technique selected but also by the underlying mechanisms of the technique and the sensitivity of the resulting PHT to drug intervention.To study the effects of volatile anesthetics on right ventricular function during acute PHT, we aimed to develop a large animal model with stable increased afterload over several hours and minimal direct effects on cardiac function. We tested embolization techniques with different sizes of microbeads and the infusion of U46619. We favored pigs over dogs and goats because of the thickness of the arteriolar vascular muscle layer and the degree of collateral ventilation, which thus make the sensitivity of the pulmonary vasculature of swine more representative of that in humans.     

Prevalence of Pulmonary Hypertension in the General Population: The Rotterdam Study

Background

Pulmonary hypertension is characterized by increased pulmonary artery pressure and carries an increased mortality. Population-based studies into pulmonary hypertension are scarce and little is known about its prevalence in the general population. We aimed to describe the distribution of echocardiographically-assessed pulmonary artery systolic pressure (ePASP) in the general population, to estimate the prevalence of pulmonary hypertension, and to identify associated factors.

Methods

Participants (n = 3381, mean age 76.4 years, 59% women) from the Rotterdam Study, a population-based cohort, underwent echocardiography. Echocardiographic pulmonary hypertension was defined as ePASP>40 mmHg.

Results

Mean ePASP was 26.3 mmHg (SD 7.0). Prevalence of echocardiographic pulmonary hypertension was 2.6% (95%CI: 2.0; 3.2). Prevalence was higher in older participants compared to younger ones (8.3% in those over 85 years versus 0.8% in those between 65 and 70), and in those with underlying disorders versus those without (5.9% in subjects with COPD versus 2.3%; 9.2% in those with left ventricular systolic dysfunction versus 2.3%; 23.1% in stages 3 or 4 left ventricular diastolic dysfunction versus 1.9% in normal or stage 1). Factors independently associated with higher ePASP were older age, higher BMI, left ventricular diastolic dysfunction, COPD and systemic hypertension.

Conclusion

In this large population-based study, we show that pulmonary hypertension as measured by echocardiography has a low prevalence in the overall general population in the Netherlands, but estimates may be higher in specific subgroups, especially in those with underlying diseases. Increased pulmonary arterial pressure is likely to gain importance in the near future due to population aging and the accompanying prevalences of underlying disorders.     

金标法与免疫发光法检测CEA 在健康体检中的应用

目的:探讨金标法和免疫发光法检测CEA在健康体检中的应用价值。方法:对728例健康体检的个人同时应用金标法和免疫发光法测定CEA,对结果进行分析。结果:金标法测定的阳性率为0.69%,免疫发光法测定的阳性率为0.41%,两者具有高度一致性。结论:对健康体检人群应先用金标法进行定性,对阳性结果再用免疫发光法进行定量。     

金标法与免疫发光法检测CEA在健康体检中的应用

目的：探讨金标法和免疫发光法检测CEA在健康体检中的应用价值。方法：对728例健康体检的个人同时应用金标法和免疫发光法测定CEA,对结果进行分析。结果：金标法测定的阳性率为0．69％,免疫发光法测定的阳性率为0．41％,两者具有高度一致性。结论：对健康体检人群应先用金标法进行定性,对阳性结果再用免疫发光法进行定量。     

Evaluation of Physical and Functional Protein-Protein Interaction Prediction Methods for Detecting Biological Pathways

Background

Cellular activities are governed by the physical and the functional interactions among several proteins involved in various biological pathways. With the availability of sequenced genomes and high-throughput experimental data one can identify genome-wide protein-protein interactions using various computational techniques. Comparative assessments of these techniques in predicting protein interactions have been frequently reported in the literature but not their ability to elucidate a particular biological pathway.

Methods

Towards the goal of understanding the prediction capabilities of interactions among the specific biological pathway proteins, we report the analyses of 14 biological pathways of Escherichia coli catalogued in KEGG database using five protein-protein functional linkage prediction methods. These methods are phylogenetic profiling, gene neighborhood, co-presence of orthologous genes in the same gene clusters, a mirrortree variant, and expression similarity.

Conclusions

Our results reveal that the prediction of metabolic pathway protein interactions continues to be a challenging task for all methods which possibly reflect flexible/independent evolutionary histories of these proteins. These methods have predicted functional associations of proteins involved in amino acids, nucleotide, glycans and vitamins & co-factors pathways slightly better than the random performance on carbohydrate, lipid and energy metabolism. We also make similar observations for interactions involved among the environmental information processing proteins. On the contrary, genetic information processing or specialized processes such as motility related protein-protein linkages that occur in the subset of organisms are predicted with comparable accuracy. Metabolic pathways are best predicted by using neighborhood of orthologous genes whereas phyletic pattern is good enough to reconstruct central dogma pathway protein interactions. We have also shown that the effective use of a particular prediction method depends on the pathway under investigation. In case one is not focused on specific pathway, gene expression similarity method is the best option.     

Centre Selection for Clinical Trials and the Generalisability of Results: A Mixed Methods Study

Background

The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice.

Methods and Findings

Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists’ views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively.

Conclusions

Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize ‘generalisability’ and incorporate it at the design stage of RCTs so that results are readily transferable to ‘real world’ practice.     

混合家系遗传参数估计方法研究

针对混合家系遗传参数估计,本文在假定公畜方差组分和母畜方差组分相等这一理论基础上,通过对方差分析的期望均方组成分析,提出了新的遗传力估计方法,以及某些特殊情况下的近似估计方法。通过一个估测实例比较了几种遗传力估计方法,结果表明,本文方法与全同胞组分估计最为接近,而且遗传力标准误最小,本文近似估计方法的效果也较好。对各种方法而言,资料越不平衡其差异越大。本文方法可以在一定程度上弥补全同胞分析时,因实际资料的公母畜方差组分差异过大的缺陷,具有实际可行性。此外,由于本文方法是用单因方差分析解决二因方差分析问题,计算更为简便,并可免于计算混合家系平均亲缘相关系数。     

Application of Physical Methods to the Study of Serum Lipoprotein

Abstract

One of the primary characteristics distinguishing prokaryotic from eukaryotic cells is the absence of a nucleus with a clearly defined nuclear membrane. In prokaryotic cells the DNA is condensed into a structure called the nucleoid. This structure has also been referred to attimes as the nuclear body, prokaryotic nucleus, bacterial chromosome, folded genome, or folded bacterial chromosome. The nomenclature sometimes becomes confusing because unfolded bacterial DNA free of other components of the nucleoid has also been referred to as the bacterial chromosome. To avoid such confusion, it would be preferable to reserve the terms nucleoid or bacterial chromosome to describe the condensed prokaryotic DNA structures which have some features analogous to the eukaryotic metaphase chromosome and condensed interphase chromatin. If this convention is followed, the terms “folded chromosome” or “folded genome” become ambiguous because they could equally mean “folded nucleoid.” These latter terms will, therefore, be avoided throughout this article.     

转基因烟草荧光定量检测方法研究

依据实时定量PCR原理,参照35S启动子、NOS终止子、GUS基因和NPTII基因序列设计TaqMan引物和荧光标记探针。采用美国MJ公司OpticonTM2荧光定量PCR检测系统对烤后烟叶进行转基因定量检测技术研究,从中筛选出扩增效率高,灵敏度好的PCR引物和探针序列,同时通过对扩增体系,扩增条件的梯度实验,优化出荧光定量检测的最佳反应体系和反应条件,从而建立了转基因烟草定量检测方法。该方法经验证其检测灵敏度达到0.05％。在2003年6月参加CORESTA(国际烟草科研与合作中心)组织的国际烟草转基因定量检测合作试验中,该优化转基因烟草定量检测技术获得了较好成绩,对盲检样品检测结果评价(Z-score)列国际12家实验室之首,证明此法灵敏度高、稳定性好。     

三种方法诊断不孕症患者子宫内膜息肉的临床价值研究

目的:探讨单用阴道超声(TVS)、子宫输卵管造影(HSG)、超声子宫水造影(SIS)以及三种方法联合诊断不孕症患者子宫内膜息肉(EP)的临床价值。方法:以206例行宫腔镜联合诊刮或病检的不孕症患者为研究对象,回顾性分析各种检查方法对EP的筛查结果,评价各种检查方法的真实性、可靠性以及预测值。结果:206例不孕症中,共确诊EP患者60例,阳性率29.1%。三种检查方法中,TVS的灵敏度最高(70.0%),特异度最低(73.3%),漏诊率最低(30.0%),误诊率最高(26.7%),正确诊断指数最高(43.3%),阴性似然比最小(0.409),阴性预测值最高(85.6%);SIS检查的灵敏度最低(38.7%),漏诊率最高(61.3%),但是特异性最高(93.3%),误诊率最低(6.7%),阳性似然比最大(4.284),阳性预测值最大(66.6%),正确诊断指数最低(32.0%);HSG检查的上述各项评价指标均介于TVS和SIS之间。TVS和SIS与金标准的符合率低,Kappa值均小于0.4;HSG符合率最高(86.2%),Kappa值0.647。三种检查联合诊断的灵敏度89.3%,漏诊率10.7%,特异度91.4%,误诊率8.6%,正确诊断指数80.7%,阳性似然比10.384,阴性似然比0.117,符合率89.3%,Kappa值0.792,阳性预测值83.3%,阳性预测值94.6%。结论:对于宫腔可能存在内膜息肉的不孕症患者,单一采用阴道超声检查、子宫输卵管造影或超声子宫水造影方法的灵敏度均较低,漏诊率高,与金标准的一致性较差,而三种方法联合用于诊断不孕症患者EP的真实性、可靠性及预测值均较好。     

Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension

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A Comparison Study of Canonical Correlation Analysis Based Methods for Detecting Steady-State Visual Evoked Potentials

Canonical correlation analysis (CCA) has been widely used in the detection of the steady-state visual evoked potentials (SSVEPs) in brain-computer interfaces (BCIs). The standard CCA method, which uses sinusoidal signals as reference signals, was first proposed for SSVEP detection without calibration. However, the detection performance can be deteriorated by the interference from the spontaneous EEG activities. Recently, various extended methods have been developed to incorporate individual EEG calibration data in CCA to improve the detection performance. Although advantages of the extended CCA methods have been demonstrated in separate studies, a comprehensive comparison between these methods is still missing. This study performed a comparison of the existing CCA-based SSVEP detection methods using a 12-class SSVEP dataset recorded from 10 subjects in a simulated online BCI experiment. Classification accuracy and information transfer rate (ITR) were used for performance evaluation. The results suggest that individual calibration data can significantly improve the detection performance. Furthermore, the results showed that the combination method based on the standard CCA and the individual template based CCA (IT-CCA) achieved the highest performance.     

Assessing the Quality of Care for Pneumonia in Integrated Community Case Management: A Cross-Sectional Mixed Methods Study

Background

Pneumonia is the leading infectious cause of mortality in children under five worldwide. Community-level interventions, such as integrated community case management, have great potential to reduce the burden of pneumonia, as well as other diseases, especially in remote populations. However, there are still questions as to whether community health workers (CHW) are able to accurately assess symptoms of pneumonia and prescribe appropriate treatment. This research addresses limitations of previous studies using innovative methodology to assess the accuracy of respiratory rate measurement by CHWs and provides new evidence on the quality of care given for children with symptoms of pneumonia. It is one of few that assesses CHW performance in their usual setting, with independent re-examination by experts, following a considerable period of time post-training of CHWs.

Methods

In this cross-sectional mixed methods study, 1,497 CHW consultations, conducted by 90 CHWs in two districts of Luapula province, Zambia, were directly observed, with measurement of respiratory rate for children with suspected pneumonia recorded by video. Using the video footage, a retrospective reference standard assessment of respiratory rate was conducted by experts. Counts taken by CHWs were compared against the reference standard and appropriateness of the treatment prescribed by CHWs was assessed. To supplement observational findings, three focus group discussions and nine in depth interviews with CHWs were conducted.

Results and Conclusion

The findings support existing literature that CHWs are capable of measuring respiratory rates and providing appropriate treatment, with 81% and 78% agreement, respectively, between CHWs and experts. Accuracy in diagnosis could be strengthened through further training and the development of improved diagnostic tools appropriate for resource-poor settings.     

Pentraxin3 in Chronic Thromboembolic Pulmonary Hypertension: A New Biomarker for Screening from Remitted Pulmonary Thromboembolism

Background

Pentraxin3 (PTX3) is a protein, which has multifaceted effects on innate immunity, angiogenesis, and vascular remodeling then could be a disease marker of acute myocardial infarction, heart failure, vasculitis. In addition, PTX3 has been recognized as a biomarker for pulmonary arterial hypertension, however whether it is the case in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. Therefore, we investigated whether PTX3 would be a useful biomarker for detecting CTEPH with respect to differentiation from stable pulmonary thromboembolism (PTE), in comparison to other biomarkers.

Methods

Plasma PTX3 and brain natriuretic peptide (BNP) levels were measured in 70 patients with CTEPH at their first diagnostic right heart catheterization (CTEPH group) and in 20 patients with clinically stable PTE more than three months after the acute episode (control group). The levels of plasma C-reactive protein (CRP) and heart-type fatty acid-binding protein (H-FABP) were also analyzed to compare the diagnostic ability of these biomarkers.

Results

The mean level of PTX3 (ng/mL) was significantly higher in the CTEPH group than in the control group (5.51±4.53 versus 2.01±0.96, respectively), and PTX3 levels had mild negative correlation with cardiac output. BNP levels were also higher in the CTEPH group and better correlated with pulmonary hemodynamics than PTX3. However, a receiver operating characteristic (ROC) curve showed PTX3 levels were better for detecting CTEPH, and could detect CTEPH patients with less severe pulmonary hemodynamics and low plasma BNP levels. There was no significant increase in CRP and H-FABP levels in the CTEPH patients.

Conclusions

Plasma PTX3 level was the most sensitive biomarker of CTEPH. Although plasma PTX3 levels did not correlate with the severity of the pulmonary hemodynamics compared to BNP, high levels in clinically stable patients following PTE should prompt a further work-up for CTEPH, which may lead to an early diagnosis.