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Background: Pulmonary transit time (PTT) obtained from contrast echocardiography is a marker of global cardiopulmonary function. Pulmonary blood volume (PBV), derived from PTT, may be a noninvasive surrogate for left-sided filling pressures, such as pulmonary artery wedge pressure (PAWP). We sought to assess the relationship between PBV obtained from contrast echocardiography and PAWP., Methods: Participants were adult survivors of childhood cancer that had contrast echocardiography performed nearly simultaneously with right-heart catheterization. PTT was derived from time-intensity curves of contrast passage through the right ventricle (RV) and left atrium (LA). PBV relative to overall stroke volume (rPBV) was estimated from the product of PTT and heart rate during RV-LA transit. PAWP was obtained during standard right-heart catheterization. The Spearman correlation coefficient was used to assess the relationship between rPBV and PAWP., Results: The study population consisted of 7 individuals who had contrast echocardiography and right-heart catheterization within 3 hours of each other. There was a wide range of right atrial (1-17 mm Hg), mean pulmonary artery (18-42 mm Hg), and PAW pressures (4-26 mm Hg) as well as pulmonary vascular resistance (<1-6 Wood Units). We observed a statistically significant correlation between rPBV and PAWP (r = .85; P = .02)., Conclusion: Relative PBV derived from contrast echocardiography correlates with PAWP. If validated in larger studies, rPBV could potentially be used as an alternative to invasively determine left-sided filling pressure., (© 2018 Wiley Periodicals, Inc.)

Purpose: Hypoglycemia is associated with increased mortality, but the role of its etiology is unclear. This study aimed to examine the impact of hypoglycemia etiology on mortality risk among critically ill patients., Methods: This single-center, retrospective, cohort study evaluated adult patients admitted to the medical or surgical intensive care unit, who experienced medication-induced or spontaneous hypoglycemia (blood glucose <70 mg/dL) during intensive care unit admission. Patients who became hypoglycemic following receipt of glucose-lowering therapy within a predefined time period were categorized in the medication-induced group. Periods were determined for each agent based on expected pharmacokinetics in critically ill patients. Patients who became hypoglycemic with no identifiable cause were categorized in the spontaneous group. Primary analysis compared medication-induced and spontaneous hypoglycemia with a primary endpoint of all-cause hospital mortality. Secondary analyses stratified patients by diabetes, severity of hypoglycemia, and glycemic variability., Results: A total of 642 patients were eligible for inclusion (305 medication-induced and 337 spontaneous). When adjusted for covariates, no difference in hospital mortality was observed based on hypoglycemia etiology (odds ratio, 1.22 [0.77-1.93]; P=.39). Regardless of etiology, hypoglycemic severity, frequency, and glycemic variability were significantly associated with higher odds of hospital mortality. Hypoglycemic etiology did not impact hospital mortality when patients were stratified by presence or absence of diabetes., Conclusions: Medication-induced hypoglycemia appears to be equally harmful as spontaneous hypoglycemia during critical illness. Future studies should aim to identify strategies to minimize hypoglycemia regardless of etiology, while also minimizing glycemic variability associated with hypoglycemia treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF inhibitor (TNFi) and nonbiological immunosuppressant (NBIS), compared with NBIS alone for autoimmune diseases. Secondly, we aimed at comparing this risk between the different TNFis. We conducted a disproportionality analysis (case/noncase study) from the French National PharmacoVigilance Database. We selected all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal 3-month exposure to NBIS. Noncases were all the other reports. We searched for exposure to TNFi and calculated reporting odds ratios (RORs), stratified by condition and type of cancer and adjusted by age, gender, history of cancer, type of NBIS and year of reporting. Of the 1918 reports included in the study population, 217 were cases (135 solid and 82 blood cancers). A safety signal was found in rheumatoid arthritis (RA) (ROR: 5.43, 95% CI[3.52-8.38]) particularly for nonmelanoma skin cancer (NMSC) (20.17[2.49-163.36]), and in psoriasis/psoriatic arthritis (3.45[1.09-10.92]). No signal was found in inflammatory bowel diseases (IBD) and ankylosing spondylitis, whatever the type of cancer. There was no difference between TNFis. This study puts the argument of an increased risk of cancer (particularly NMSC) in patients with rheumatoid arthritis exposed to TNFi and NBIS compared with NBIS alone, but not in IBD and ankylosing spondylitis patients. No signal was detected for melanoma potentially related to the lack of power. The signal seems similar whatever the TNFi., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

Objective: Describing the factors associated with direct oral anticoagulants (DOA) prescription in patients with atrial fibrillation (AF)., Method: This study was performed in Toulouse on a cohort of patients received in rhythmology consultation, treated with vitamin K antagonists (VKA) or DOA for AF. A multivariate model was performed using logistic regression to describe the factors associated with DOA prescription and secondly, those associated with discontinuation of the anticoagulant., Results: Among the 140 patients included, 96 (66%) were treated with VKA and 48 (34%) with DOA. Recent AF diagnosis (OR 7.52, 95% CI [2.41;23.29], p = 0.001), previous exposure to VKA (OR 17.11, 95% CI [4.48;60.91], p<0.001), and no current exposure to anti-platelet agents (APA) (OR 7.69, 95% CI [1.22; 50.00], p = 0.030) were associated to DOA prescription. Discontinuation of the anticoagulant (n=24) was associated to DOA intake (OR 2.71, 95% CI [1.21; 6.08], p = 0.016)., Discussion: DOA are less prescribed than VKA in patients treated with APA. DOA switch to VKA was not systematic in patients diagnosed for a long time. However, international normalized ratio (INR) values were stable in most of patients treated with VKA at the switching to DOA. A more powerful study would confirm the factors associated with DOA prescription., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

Aims: Pulmonary transit time (PTT; the time for ultrasound contrast to travel from the right ventricle [RV] to the left atrium) may provide a single metric that reports on cardiopulmonary function while overcoming some of the challenges of standard echocardiographic measures. We conducted a pilot study to test the feasibility and reproducibility of echocardiographically derived PTT and to determine its association with established measures of cardiopulmonary function., Methods and Results: A total of 39 patients receiving clinically indicated ultrasound contrast were prospectively enrolled. PTT was measured in the apical four-chamber view using commercially available software. Reproducibility and inter-observer agreement were assessed in 9 patients. PTT was correlated with established measures of left ventricular systolic and diastolic function, RV function, and pulmonary vascular status. PTT could be measured in 89% (33/37) of patients without a contraindication to ultrasound contrast; all measurements from the last 20 patients were interpretable and obtained independently by a sonographer. Reproducibility and inter-observer agreement were excellent. PTT correlated well with standard echocardiographic indicators of cardiac status. A PTT >4.5 seconds accurately identified all but 1 patient with cardiopulmonary dysfunction., Conclusions: This pilot study demonstrates that measurement of PTT using ultrasound contrast is highly reproducible, accurately reflects global cardiopulmonary function across a range of cardiopulmonary disease, and can be readily obtained by an independent sonographer. Further studies are needed to determine whether PTT has incremental value in diagnosis and prognosis compared to conventional echocardiographic parameters., (© 2015, Wiley Periodicals, Inc.)

In the nucleus of the tractus solitarii (NTS), a large proportion of neurones express transient A-type potassium currents (I KA) having deep influence on the fidelity of the synaptic transmission of the visceral primary afferent inputs to second-order neurones. Up to now, the strong impact of I KA within the NTS was considered to result exclusively from its variation in amplitude, and its molecular correlate(s) remained unknown. In order to identify which Kv channels underlie I KA in NTS neurones, the gating properties and the pharmacology of this current were determined using whole cell patch clamp recordings in slices. Complementary information was brought by immunohistochemistry. Strikingly, two neurone subpopulations characterized by fast or slow inactivation time courses (respectively about 50 and 200 ms) were discriminated. Both characteristics matched those of the Kv4 channel subfamily. The other gating properties, also matching the Kv4 channel ones, were homogeneous through the NTS. The activation and inactivation occurred at membrane potentials around the threshold for generating action potentials, and the time course of recovery from inactivation was rapid. Pharmacologically, I KA in NTS neurones was found to be resistant to tetraethylammonium (TEA), sea anemone toxin blood-depressing substance (BDS) and dendrotoxin (DTX), whereas Androctonus mauretanicus mauretanicus toxin 3 (AmmTX3), a scorpion toxin of the α-KTX 15 family that has been shown to block all the members of the Kv4 family, inhibited 80 % of I KA irrespectively of its inactivation time course. Finally, immunohistochemistry data suggested that, among the Kv4 channel subfamily, Kv4.3 is the prevalent subunit expressed in the NTS.

Objective: To use two different techniques to assess adherence of patients treated with antiosteoporotic drug., Methods: This monocentric transversal study was performed on a 6 months period, on patients of a single French pharmacy treated with antiosteoporotic drugs. Adherence was assessed crossing 2 techniques (patient autoquestionnaire and medication possession ratio measurement). Statistical analysis consisted in a description of the population study and a multivariate logistic regression to identify the factors associated with a lack of observance., Results: Using the two techniques, the lack of adherence was estimated to be between 14 and 55%. Adherence was better in patients who were given dietetic advice or information about the usefulness of physical activity and worse in patients who reached menopause less than 23 years ago., Conclusion: A better identification of patients with a lack of observance is possible by crossing several techniques to assess adherence of the patient to his antiosteoporotic drug., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Although chronic hypertension is associated with long-term complications, few studies directly examine the effects of in-hospital acute hypertensive episodes in trauma patients. The aim was to determine whether there is an association between in-hospital acute hypertension and morbidity. We included trauma patients between 45 and 89 years who presented to a level I trauma center between January and September 2008. Patients were classified as either experiencing or not experiencing acute hypertensive episode(s) as defined by systolic blood pressure ≥180, or diastolic blood pressure ≥110 mmHg, or at least two readings of systolic blood pressure ≥160 or diastolic blood pressure ≥100 mmHg. The primary outcome was a composite endpoint of myocardial infarction, stroke, venous thromboembolism, new-onset atrial fibrillation, or acute kidney injury. At least one acute hypertensive episode occurred in 42.6% (69/162) of patients. A total of 10.5% patients developed the composite endpoint, 17.4% in the acute hypertensive episode group compared to 5.4% in the non-hypertensive group, p = 0.012. Patients in the acute hypertensive group were more likely to require an intensive care unit admission compared to the non-hypertensive group (33.3 versus 14.0%, p = 0.004). Of the 17 patients who developed an acute hypertensive episode and met the primary endpoint, 10 were on home antihypertensive medications. Of those, four were restarted on all medications initially, three on some, two were started on new medications, and one was not resumed on home medications. Development of acute hypertensive episode(s) in older trauma patients was associated with an increase in the composite endpoint. Prospective studies are needed.

To evaluate the interaction between the levels of dietary concentrate and linseed oil (LO) on milk fatty acid (FA) profile, 24 Holstein cows were used in a randomised complete block design based on days in milk, with a 2×2 factorial arrangement of treatments. Within each block, cows were fed one of four experimental diets containing 30% concentrate (LC) or 70% concentrate (HC), without LO (NLO) or with LO supplemented at 3% of dietary dry matter. Milk FA profiles were analysed with a special emphasis on the intermediates of the predominant trans-11, and a putative trans-13 pathways of ruminal biohydrogenation of cis-9, cis-12, cis-15 18:3. Feeding LO increased the concentrations of cis-9, cis-12, cis-15 18:3 and trans-11, cis-15 18:2 in milk fat, and these increases were of a higher magnitude when LO was added in HC as compared with LC diet (interaction of LO by concentrate). A treatment interaction was also observed for the level of trans-11 18:1 which was higher when feeding LO, but for which the increase was more pronounced with the LC as compared with HC diet. The concentrations of cis-15 18:1 and cis-9, trans-11, cis-15 18:3 were higher in cows fed LO, but feeding HC diets decreased milk fat content of cis-15 18:1 and a tendency for a decrease in cis-9, trans-11, cis-15 18:3 was apparent. Feeding LO increased milk fat content of trans-13 18:1 and cis-9, trans-13 18:2, while the concentrations of these two isomers were not affected by the level of dietary concentrates. The isomer cis-9, trans-13, cis-15 18:3 has not been detected in any of the milk samples. In conclusion, interactions were observed between LO and dietary concentrates on the proportions of some intermediates of the trans-11 biohydrogenation pathway. The presence of trans-13 18:1 and cis-9, trans-13 18:2 supports the existence of a trans-13 pathway, but an 18:3 intermediate with a trans-13 double bond has not been identified.

Lactones are important contributors to the flavour and aroma of milk and dairy products. This study was conducted to evaluate the effects of dietary linseed oil (LO) and forage to concentrate ratio on milk lactone profile. Twenty four Holstein cows were used during a 4-week feeding trial in a randomised complete block design. Cows were fed diets containing 30% (LC) or 70% (HC) concentrate, and 0% (NLO) or 3% LO in a 2×2 factorial arrangement of treatments. Milk lactone profile was evaluated using the solid phase microextraction technique. The highest levels of δ-lactones (δ-6:0, δ-8:0, δ-10:0, and δ-12:0) were found with the LC/NLO diet. These concentrations were then decreased when cows received either a high level of concentrate or supplemental LO, but these effects were not additive (interaction of LO by concentrate, P<0·01). An interaction of LO by concentrate (P<0·01) was also noted on milk γ-12:0 for which the highest concentration was observed when supplementing LO in HC diet, while no effect was apparent when LO was added in LC diet. Moreover, feeding HC increased the level of γ-12:1 in milk as compared with LC, while LO had no effect on this γ-lactone. Finally, γ-12:2 was not detected in any of the milk samples studied. Organoleptic properties of milk were evaluated in a triangle test showing that a significant number of assessors perceived a difference between milk from cows fed LC/NLO as compared with milk from cows fed HC/LO. The sensory evaluation was completed by a ranking test where the intensities of fresh lactic, foreign and global flavours were not different between treatments. In conclusion, feeding LO in HC diet modified milk lactone profile with a shift toward more γ- and less δ-lactones as compared with LC diet not supplemented with LO. A difference was perceived in a triangle test between milk from these two treatments, but the sensory attributes responsible for this difference have not been identified in the current trial.

Context: Gathering information on the circumstances that give rise to unintentional domestic non-fire related carbon monoxide poisoning and the associated morbidity and mortality is not straightforward because the diagnosis is so often missed in life., Methods: We searched Newsbank and related databases (at least 332 sources, UK and Republic of Ireland) for reports of domestic carbon monoxide poisoning, 1986-end 2011 inclusive. The search terms were 'carbon monoxide AND (house* OR home* OR caravan* OR tent*) NOT (work OR fire OR suicide*)'. Newsbank includes full-text articles from 19 UK national newspapers and over 140 UK & Irish regional and local newspapers and periodicals., Results and Discussion: There were reports of 348 incidents (880 victims: 334 male, 352 female, 194 sex not stated). Reports of incidents increased from 1986 (1) to 2011 (28). There were 298 deaths (169 male, 124 female, 5 sex not reported). The likelihood of a fatal outcome increased with age for both males and females (28%, 1-9 years; 71%, 80 + years). The source of carbon monoxide was often a central heating or water boiler (48% of 244 incidents). Many incidents (49%) occurred in private dwellings. However, incidents in caravans, tents, sheds and outhouses had a much higher death rate. If a victim was discovered alive chances of survival were relatively good (87%), even if found unconscious. The estimated duration of carbon monoxide exposure ranged from minutes to years in both fatal and non-fatal incidents. Pets were recorded in 31 incidents (17 died). In 5 cases, carbon monoxide poisoning was identified through illness or death of a pet. Prosecutions were recorded in 49 incidents and at least 7 custodial (prison) sentences resulted, with 34 further convictions resulting in a fine. Charges were preferred against either an installer/maintenance engineer (42%), or the landlord (31%)., Conclusion: Deaths and permanent injuries from unintentional domestic non-fire related carbon monoxide poisoning continue. Survival rates are relatively high if poisoning is diagnosed in life, but warning signs are often missed and inappropriate behavior such as placing barbecues in tents and failure to perform proper safety checks by gas appliance fitters still kills.

Introduction: Adhesions to mesh/tacks in laparoscopic ventral hernia repair are often cited as reasons not to adopt its evidence-based superiority over conventional open methods. This pilot study assessed the occurrence of adhesions to full-sized Polypropylene and Gore-tex DualMesh Plus meshes and the possibility for adhesion prevention using fibrin sealant., Methods: Two 10-cm to 15-cm pieces of mesh were placed and fixed laparoscopically in pigs (25kg to 55kg). Group I: 2 animals with Polypropylene mesh on one side and DualMesh on other side. Group II: 2 animals with DualMesh on each side with fibrin sealant applied to the periphery of mesh and staples to one side. Group III: 1 animal with 2 pieces of Polypropylene mesh with fibrin sealant applied to the entire mesh. All animals underwent laparoscopy 3 months later to assess the extent of adhesions, and full-thickness specimens were removed for histological evaluation., Results: More Polypropylene mesh was involved in adhesions than DualMesh. However, with the DualMesh involved in adhesions, more of the surface area was involved in forming adhesions than with Polypropylene mesh. None of the implanted DualMesh had visceral adhesions, while 2 out of 3 Polypropylene meshes had adhesions to both the liver and spleen but none to the bowel. Implanted Polypropylene mesh with fibrin sealant had no adhesions. DualMesh had shrunk more significantly than Polypropylene mesh. Histological evaluation showed absence of acute inflammatory response, significantly more chronic inflammatory response to DualMesh compared to Polypropylene and complete mesothelialization with both meshes. There was extensive collagen deposition between Polypropylene mesh fibers, while fibrosis occurred on both sides of DualMesh with synovial metaplasia over its peritoneal surface akin to encapsulation., Conclusions: DualMesh caused fewer omental and visceral adhesions than Polypropylene mesh did. Fibrin sealant eliminated adhesions to DualMesh and prevented adhesions to Polypropylene mesh when applied over the entire surface. These results support our current use of DualMesh and fibrin sealant in LVHR.

Ozone (O(3)), a major component of air pollution, has considerable impact on public health. Besides the well-described respiratory tract inflammation and dysfunctions, there is accumulating evidence indicating that O(3) exposure affects brain functions. However, the mechanisms through which O(3) exerts toxic effects on the brain remain poorly understood. This work aimed at precisely characterizing CNS neuronal activation after O(3) inhalation using Fos staining in adult rat. We showed that, together with lung inflammation, O(3) exposure caused a sustained time- and dose-dependent neuronal activation in the dorsolateral regions of the nucleus tractus solitarius overlapping terminal fields of lung afferents running in vagus nerves. Furthermore, we highlighted neuronal activation in interconnected central structures such as the caudal ventrolateral medulla, the parabrachial nucleus, the central nucleus of the amygdala, the bed nucleus of the stria terminalis and the paraventricular hypothalamic nucleus. In contrast, we did not detect any neuronal activation in the thoracic spinal cord where lung afferents running in spinal nerves terminate. Overall, our results demonstrate that O(3) challenge evokes a lung inflammation that induces the activation of nucleus tractus solitarius neurons through the vagus nerves and promotes neuronal activation in stress-responsive regions of the CNS., (© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)

Concern about adverse health effects arising out of human exposure to polluted seawater through bathing and other forms of aquatic recreation has led to the development of various quality criteria and standards worldwide. Attempts at quantifying health hazards from polluted recreational waters have been made in several Mediterranean countries through the conduction of epidemiological studies aimed at establishing direct correlation between the microbiological quality of the water and health effects on exposed population groups. This article provides an overview on the development of the criteria and standards for coastal recreational waters in the Mediterranean by examining the evolution of the WHO guidelines, the WHO/UNEP interim criteria for bathing waters and the EU Directives. It also provides a brief account of the various quality criteria and standards for coastal recreational waters in current use in all the Mediterranean countries.

The relationships between lower limb strength and two Australian football (AF) skills were assessed for 19 sub-elite AF players. Knee extension (KE) and knee flexion (KF) strength were assessed using a Biodex isokinetic dynamometer at angular velocities of 60, 240 and 360 degrees/sec. The two AF skills evaluated were running vertical jump (VJ) and kicking performance (KP). VJ performance was defined as the maximal jump height measured with a Yardstick device. KP was gauged through video analysis, as the post-contact resultant ball velocity (BV) during maximal effort drop punt kicking. Strength was measured as the isokinetic peak torque (PT value. No significant correlations were detected between the isokinetic knee strength values and maximal kicking velocity. Low to moderate significant correlations (r = 0.55 - 0.69, p < 0.05) were detected between the isokinetic measures and VJ height. It may be inferred that additional strengthening of the knee musculature may enhance running VJ performance, but not necessarily kicking velocity for this group of sub-elite AF players.

A number of bacterial, viral and other diseases can be contracted by man through exposure to sewage-polluted bathing-water or beach sand. The increasing use of the sea for recreation has led to major concern regarding health hazards to both local and tourist populations. Epidemiological studies attempting to correlate microbiological water quality with health effects have produced different results, leading to a wide variation in recreational water quality criteria and standards applied, and to considerable controversy regarding their implementation. The Mediterranean provides a good example of a problem region where health risks are accentuated as a result of high utilization of bathing areas coupled with long exposure periods. Coastal pollution by sewage is still a major concern and control measures vary considerably. A number of microbiological/epidemiological studies have been carried out since 1953 in an attempt to define the levels of risk following exposure to different concentrations of bacteria in bathing waters. Most of these have been prospective studies whose design involved subject recruitment on the beach itself, classification of swimmers on the basis of immersion of the head in the water, and follow-up interviews after 7-10 days, together with a system for validation of gastrointestinal symptomatology. Practically all studies showed higher morbidity among bathers as compared to non-bathers, but correlation between specific symptoms and bacterial indicator concentrations varied considerably. On the basis of the 1972-1978 Cabelli Environmental Protection Agency (EPA) study in the United States of America, later developed by EPA into a recommended health-effects criterion for marine recreational waters, one would expect 25-40 gastrointestinal cases per 1,000 persons exposed to seawater containing 100 enterococci per 100 ml. Extrapolation of these figures to annual bathing populations indicates the potential magnitude of the problem. Much more work is needed however before a satisfactory dose-response relationship is obtained, principally because of confounding factors inherent in all studies carried out so far, which still require a solution.