Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Almost continuity vs closure continuity

summary:We provide an answer to a question: under what conditions almost continuity in the sense of Husain implies closure continuity

Application of quantitative Raman spectroscopy for the monitoring of polymorphic transformation in crystallization processes using a good calibration practice procedure

Polymorphism is the property of a substance to have more than one crystalline form. Polymorphic forms of the same chemical compound can have different physical and chemical properties that can strongly affect the manufacturing process. For this reason, determining and monitoring polymorphic transformations have become very important, especially in pharmaceutical industry. Significant work has been developed for the calibration of Raman spectroscopy to monitor the presence and amount of solid polymorphs in suspensions during crystallization, as well as the liquid concentration. Nevertheless, a clear and systematic approach to Raman calibration is missing in the literature. The present work has the aim of developing a methodical strategy for Raman calibration, taking into account the principal factors that can affect the Raman spectra of a specific compound in solution, such as solid type, solute concentration, temperature, crystal size and suspension density. Univariate and multivariate calibration techniques were investigated using pre-processing techniques to optimize the signal. The results are combined in a systematic "good calibration practice" (GCP) procedure, proposed for the first time in this work. The approach has been applied for the quantitative monitoring of the polymorphic transformation of ortho-aminobenzoic acid (OABA). © 2013 The Institution of Chemical Engineers

Active polymorphic feedback control of crystallization processes using a combined raman and ATR-UV/Vis spectroscopy approach

The nucleation of the metastable form of a substance or of a mixture of more forms is very common in polymorphic crystallization. Additionally, in industry seed may contain a variable amount of metastable polymorph as impurity, resulting from previous batches or milling, which may compromise the desired outcome of obtaining product of the stable polymorphic form. The natural polymorphic conversion into the stable form is often too slow compared to the normal batch times. In this work, a control strategy to quickly obtain crystals of pure stable form was developed. An active polymorphic feedback control (APFC) strategy is proposed, based on the use of a combination of Raman and ATR-UV/vis spectroscopy using a hierarchical control implementation. The approach detects the formation of the polymorphic mixture and eliminates the metastable form by triggering a controlled dissolution cycle and allowing the growth of the stable form using supersaturation control. A calibration-based approach is used for the solute concentration measurement for the supersaturation control, while for the Raman measurement a calibration-free technique is applied based on the identification of a specific peak in the spectrum associated with the presence of the metastable form. The approach is evaluated in the case of the cooling crystallization of ortho-aminobenzoic acid, used as a model system. It is shown that the proposed APFC technique can lead to pure polymorphic forms in the case of an unseeded crystallization process where nucleation of polymorph mixtures occurs or for seeded crystallization with contaminated seed with unwanted polymorph impurity. © 2014 American Chemical Society

Raman, UV, NIR, and Mid-IR Spectroscopy with Focused Beam Reflectance Measurement in Monitoring Polymorphic Transformations

Raman, UV, NIR, and IR spectroscopy are commonly used techniques to monitor solute concentration and solid composition during crystallization processes of polymorphic compounds. Since a comprehensive study and comparison of the ability of these techniques to detect polymorphic transformation in the same system has not been performed yet, this work aimed at developing a complete quantitative calibration model that describes the process in terms of solute concentration and solid composition for each technique. A comparison between the different process analytical technology tools was conducted using various physical and mathematical approaches. Chemometrics techniques, multivariate and univariate approaches, and different regression techniques were tested and an integrated calibration model is proposed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

In situ monitoring of polymorphic transformations using a composite sensor array of Raman, NIR, and ATR-UV/vis spectroscopy, FBRM, and PVM for an intelligent decision support system

Raman spectroscopy, particle vision and measurement (PVM), and infrared spectroscopy have already been used singularly to detect nucleation and polymorphic transformations during crystallization processes as well as to analyze powder mixtures of multiple polymorphic forms. However, a comprehensive study and comparison of these techniques used simultaneously with integration of the signals during polymorphic transformation has not been performed to date. The aim of the present work is to compare the effectiveness of Raman spectroscopy, near-infrared spectroscopy, and PVM to detect nucleation and polymorphic transformations during crystallization processes. The information from focused beam reflectance measurement (FBRM) and attenuated total reflection ultraviolet/visible (ATR-UV/vis) probes were also used simultaneously in the same system to validate and integrate the results obtained by the other probes. This paper illustrates for the first time of the use of a composite sensor array (CSA) that truly integrates the signals from a variety of process analytical tools for better information extraction and more robust detection of various crystallization mechanisms. The proposed principal component analysis-based signal integration and the CSA can be used as the bases for an intelligent decision support system for crystallization processes, which can automatically detect various mechanisms occurring during the process, as well as a framework for the automated selection of the optimal minimal sensor configurations for the robust detection of these events

Modeling and Simulation of Gas Pipeline Network for Operational and Infrastructural Decisions

10.1016/S1570-7946(09)70076-8Computer Aided Chemical Engineering26453-45