Aims: An evaluation was made of the prevalence of Legionella species in hot water distribution systems in the city of Bologna (Italy) and their possible association with bacterial contamination ...(total counts and Pseudomonadaceae) and the chemical characteristics of the water (pH, Ca, Mg, Fe, Mn, Cu, Zn and Total Organic Carbon, TOC).
Methods and Results: A total of 137 hot water samples were analysed: 59 from the same number of private apartments, 46 from 11 hotels and 32 from five hospitals, all using the same water supply. Legionella species were detected in 40·0% of the distribution systems, L. pneumophila in 33·3%. The highest colonization was found in the hot water systems of hospitals (93·7% of samples positive for L. pneumophila, geometric mean: 2·4 × 103 CFU l−1), followed by the hotels (60·9%, geometric mean: 127·3 CFU l−1) and the apartments with centralized heating (41·9%, geometric mean: 30·5 CFU l−1). The apartments with independent heating systems showed a lower level of colonization (3·6% for Legionella species), with no evidence of L. pneumophila. Correlation analysis suggests that copper exerts an inhibiting action, while the TOC tends to favour the development of L. pneumophila. No statistically significant association was seen with Pseudomonadaceae, which were found at lower water temperatures than legionellae and in individual distribution points rather than in the whole network.
Conclusions: The water recirculation system used by centralized boilers enhances the spreading of legionellae throughout the whole network, both in terms of the number of colonized sites and in terms of CFU count.
Significance and Impact of the Study: Differences in Legionella colonization between types of buildings are not due to a variation in water supply but to other factors. Besides the importance of water recirculation, the study demonstrates the inhibiting action of copper and the favourable action of TOC on the development of L. pneumophila.
Summary
Background Capsule endoscopy can identify small bowel mucosal inflammatory change. However, there has been no validated index for capsule endoscopy findings. This manuscript documents the ...development of such an index.
Aim To develop a capsule endoscopy scoring index for small bowel mucosal inflammatory change.
Methods The index was created in four separate steps. First, parameters and descriptors of inflammatory change were identified. Secondly, blinded readers prospectively graded the presence or absence of each parameter on de‐identified videos and graded a perceived global assessment of overall severity. Thirdly, the individual parameters and descriptors were ranked in order of severity. Fourthly, values for each parameter were created using the descent gradient methodology. The premise was to assure that the final numerical score reflected the global assessment and that the global assessment agreed with the ranking of finding severity. Results were compiled for the three categories: no or clinically insignificant change, mild change, and moderate or severe change. Thresholds were determined.
Results The final index includes three parameters: villous oedema, ulcer and stenosis. A score <135 is designated normal or clinically insignificant mucosal inflammatory change, a score between 135 and 790 is mild, and a score ≥790 is moderate to severe.
Conclusion This capsule endoscopy score provides a common language to quantify small bowel inflammatory changes.
The thionation reaction of carbonyl compounds with Lawesson’s reagent (LR) has been studied using density functional theory methods and topological analyses. After dissociation of LR, the reaction ...takes place through a two-step mechanism involving (i) a concerted cycloaddition between one monomer and the carbonyl compound to form a four-membered intermediate and (ii) a cycloreversion leading to the thiocarbonyl derivative and phenyl(thioxo)phosphine oxide. Topological analyses confirmed the concertedness and asynchronicity of the process. The second step is the rate-limiting one, and the whole process resembles the currently accepted mechanism for the lithium salt-free Wittig reaction. No zwitterionic intermediates are formed during the reaction, although stabilizing electrostatic interactions are present in initial stages. Phenyl(thioxo)phosphine oxide formed in the thionation reaction is capable of performing a second thionation, although with energy barriers higher than the first one. The driving force of the thionation reactions is the formation of trimers from the resulting monomers. In agreement with experimental observations, the amides are the most reactive when compared with esters, aldehydes, and ketones and the reaction is slightly influenced by the polarity of the solvent. Whereas for amides and esters substituents have little effect, aldehydes and ketones are influenced by both steric and electronic effects.
See also Galli M. The antiphospholipid triangle. This issue, pp 234–6.
Summary. Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high‐risk patients that ...are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described. Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐β2‐glycoprotein I (β2GPI) antibodies. Laboratory data were confirmed in a central reference laboratory. Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow‐up period was 12.2% (95%CI, 9.6–14.8) after 1 year, 26.1% (95%CI, 22.3–29.9) after 5 years and 44.2% (95%CI, 38.6–49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95%CI 1.3–4.1; P < 0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths). Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.
E. LEONI AND P.P. LEGNANI. 2001. Various sample pre‐treatment techniques and different growth media for the isolation of Legionellae from hot water supplies in public buildings were compared. A total ...of 102 hot water samples from taps and showers was examined. The highest recovery frequency was obtained with the heat pre‐treatment method and using the selective medium GVPC. However, the results differed according to the concentration of legionellas. In the case of low plate counts (≤5000 cfu l−1), the heat pre‐treatment technique gave a significantly higher percentage of positive samples compared with other techniques (P < 0·05). With increasing concentration, the differences between the procedures decreased until they became statistically not significant for concentrations above 50 000 cfu l−1. The direct inoculum method allowed a significantly higher detection of concentrations (P < 0·001) compared with heat and acid decontamination methods, which brought about a 67–68% reduction in detectable Legionellae. Heat decontamination techniques show greater sensitivity and specificity. However, they underestimate the number of legionellas. In environmental surveillance programmes, this underestimate must be taken into consideration when assessing the health risk.
The aim of this study is to formulate a new methodology based upon informational tools to detect patients with cardiac arrhythmias. As it is known, sudden death is the consequence of a final ...arrhythmia, and here lies the relevance of the efforts aimed at the early detection of arrhythmias. The information content in the time series from an electrocardiogram (ECG) signal is conveyed in the form of a probability distribution function, to compute the permutation entropy proposed by Bandt and Pompe. This selection was made seeking its remarkable conceptual simplicity, computational speed, and robustness to noise. In this work, two well-known databases were used, one containing normal sinus rhythms and another one containing arrhythmias, both from the MIT medical databank. For different values of embedding time delay τ, normalized permutation entropy and statistical complexity measure are computed to finally represent them on the horizontal and vertical axes, respectively, which define the causal plane H×C. To improve the results obtained in previous works, a feature set composed by these two magnitudes is built to train the following supervised machine learning algorithms: random forest (RF), support vector machine (SVM), and k nearest neighbors (kNN). To evaluate the performance of each classification technique, a 10-fold cross-validation scheme repeated 10 times was implemented. Finally, to select the best model, three quality parameters were computed, namely, accuracy, the area under the receiver operative characteristic (ROC) curve (AUC), and the F1-score. The results obtained show that the best classification model to detect the ECG coming from arrhythmic patients is RF. The values of the quality parameters were at the same levels reported in the available literature using a larger data set, thus supporting this proposal that uses a very small-sized feature space to train the model later used to classify. Summarizing, the attained results show the possibility to discriminate both groups of patients, with normal sinus rhythm or arrhythmic ECG, showing a promising efficiency in the definition of new markers for the detection of cardiovascular pathologies.
Essentials
Prothrombin and partial thromboplastin time (PT/PTT) measure direct oral anticoagulants (DOACs).
PT, PTT and specific tests for DOACs were performed on patients treated for atrial ...fibrillation.
Normal PT/PTT don't exclude DOAC activity and their prolongation doesn't confirm DOAC action.
The use of PT or PTT to evaluate DOAC activity could cause dangerous misinterpretations.
Summary
Background
Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been proposed to measure the effect of oral anti‐activated factor X (FXa) or anti‐activated FII drugs, respectively.
Aims
To evaluate the relationships and responsiveness of PT and APTT versus direct oral anticoagulant (DOAC) concentrations measured with specific coagulation tests performed with different platforms in four Italian anticoagulation clinics.
Methods
Six hundred and thirty‐five patients with atrial fibrillation participated in the study: 240 were receiving dabigatran, 264 were receiving rivaroxaban, and 131 were receiving apixaban. Blood was taken at trough and peak within the first month (15–25 days) of treatment. PT, APTT, diluted thrombin time (dTT) calibrated for dabigatran and anti‐FXa calibrated for rivaroxaban or apixaban were determined.
Results
For dabigatran, the correlation between APTT and dTT ranged from r = 0.80 to r = 0.62. For rivaroxaban, the correlation between the anti‐FXa assay and PT ranged from r = 0.91 to r = 0.73. For apixaban, the correlation between the anti‐FXa assay and PT was lower than for the two other drugs (r = 0.81 to r = 0.54). Despite the above significant correlations, the responsiveness of PT or APTT was relatively poor. A discrepancy between global testing and DOAC plasma concentrations was shown in a considerable proportion of patients, depending on the platform and drug, with values ranging from 6% to 62%.
Conclusions
Overall, poor responsiveness of the screening tests to DOAC concentrations was observed. PT and APTT normal values cannot exclude DOAC anticoagulant activity, and PT or APTT prolongation is not always associated with DOAC anticoagulant effect as determined with specific tests.
Essentials
Predicting recurrences may guide therapy after unprovoked venous thromboembolism (VTE).
We evaluated the DASH score in 827 patients with unprovoked VTE to verify prediction accuracy.
A ...DASH score ≤ 1 had a cumulative recurrence risk at 1 year of 3.6%, as predicted by the model.
The DASH score performed better in younger (< 65 years old) subjects.
Summary
Background
The DASH prediction model has been proposed as a guide to identify patients at low risk of recurrence of venous thromboembolism (VTE), but has never been validated in an independent cohort.
Aims
To validate the calibration and discrimination of the DASH prediction model, and to evaluate the DASH score in a predefined patient subgroup aged > 65 years.
Methods
Patients with a proximal unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin K antagonist or direct oral anticoagulant (> 3 months) and had D‐dimer measured after treatment withdrawal were eligible. The DASH score was computed on the basis of the D‐dimer level after therapy withdrawal and personal characteristics at the time of the event. Recurrent VTE events were symptomatic proximal or distal DVT/PE, and were analyzed with a time‐dependent analysis. Observed 12‐month and 24‐month recurrence rates were compared with recurrence rates predicted by the DASH model.
Results
We analyzed a total of 827 patients, of whom 100 (12.1%) had an objectively documented recurrence. As compared with the original DASH cohort, there was a greater proportion of subjects with a ‘low‐risk’ (≤ 1) DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51–1.45). The c‐statistic was lower for subjects aged > 65 years (0.54) than for younger subjects (0.72).
Conclusions
These results confirm the validity of DASH prediction model, particularly in young subjects. The recurrence risk in elderly patients (> 65 years) was, however, > 5% even in those with the lowest DASH scores.
Background: The assessment of the risk of recurrent venous thromboembolism (VTE) is important to determine the optimal duration of secondary prophylaxis. The risk can be estimated by measuring ...individual parameters reflecting hypercoagulability. Because of the large numbers of such putative parameters, the assessment in individual patients is complex. Application of global assays reflecting the pro‐/anti‐coagulant balance in vivo would be desirable. Objectives: To investigate the relationship between recurrent VTE and thrombin generation (TG). Patients‐methods: Two hundred and fifty‐four patients were followed‐up after a first episode of unprovoked, objectively documented VTE for a period of 2.7 years after discontinuation of treatment with vitamin K antagonists. TG was measured 1 month after discontinuation of treatment as endogenous thrombin potential (ETP), peak thrombin and lag‐time in the presence or absence of thrombomodulin. The study outcome was objectively documented symptomatic recurrent VTE. Results: Patients with ETP or peak (measured in the presence of thrombomodulin) of >960 nm*min or >193 nm had hazard ratios (HR) (95% CI) for recurrent VTE of 3.41 (1.34–8.68) or 4.57 (1.70–12.2) as compared with those with an ETP <563 nm*min or peak <115 nm. Patients with lag‐time <14.5 min had HR of 3.19 (1.29–7.89) as compared with those with lag‐time >20.8 min. HR for ETP, peak or lag‐time measured in the absence of thrombomodulin were smaller than those measured in the presence of thrombomodulin. Conclusions: The measurement of TG helps to identify patients at higher risk of VTE recurrence. The increased risk may be better appreciated if the test is performed in the presence of thrombomodulin.
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