Establishing a standardized quality management system for the European Health Network GA2LEN.

BACKGROUND: Quality management is increasingly important in clinical practice. The Global Allergy and Asthma European Network (GA(2)LEN) is a network of clinical and scientific excellence with originally 25 allergy centres in 16 European countries, a scientific society (European Academy of Allergology and Clinical Immunology), and a patient organization (European Federation of Allergy and Airways Diseases Patients' Associations). Although some allergy centres adhere to internal quality criteria, the implementation of a standardized quality management system for allergy centres across Europe was lacking. OBJECTIVES: To implement standardized quality criteria among allergy centres organized within GA(2)LEN and thus ensure equal standards of diagnosis and care as well as to establish a culture of continuous quality improvement. METHODS: Quality criteria covering, e.g., diagnostic and therapeutic procedures, and emergency preparedness to assure patient safety were developed and agreed upon by all 25 participating centres. To assure implementation of quality criteria, centres were audited to check quality indicators and document deviations. A follow-up survey was used to assess the usefulness of the project. RESULTS: Deviations were documented mainly in the areas of emergency care/patient safety (27.3% lacked regular emergency training of doctors and nurses; 22.7% inadequate emergency intervention equipment; 22.7% lacked critical incidence reporting/root cause analyses) and handling of extracts/pharmaceuticals (31.8% lacked temperature logs of fridges; 4.5% inadequate check of expiration dates). Quality improvement was initiated as shown by findings of re-audits. Usefulness of the project was rated high. CONCLUSION: The establishment of a quality management system with joint standards of care and harmonized procedures can be achieved in an international health network and ensures quality of care.

Delivery of asthma and allergy care in Europe.

BACKGROUND: There is no comprehensive information available concerning the way in which care is provided for those with allergic conditions in Europe. OBJECTIVE: To determine who cares for those with asthma, allergic dermatitis, and rhinitis in Europe and to determine the involvement of primary care and other healthcare professionals and the use of patient education and guidelines. METHODS: A questionnaire survey of colleagues in 43 institutions in 33 European countries with results being related to published sources of information regarding prevalence of allergic diseases in different countries and published data regarding availability of doctors and expenditure on healthcare. RESULTS: A total of 33 of 43 institutions completed the survey (76.7%) with information being obtained from 26 of the 33 countries surveyed (78.7%). There are wide differences in the use of different healthcare professionals in different countries, with those for asthma, for example, being most likely to be cared for by an allergologist in some countries and by a primary care physician in many others. There was much greater awareness of guidelines for asthma and little reported usage of guidelines in the management of those with allergic skin diseases, and while self-management education was offered most to those with asthma, there was a wide variation in the usage of group education. CONCLUSIONS: Many of the differences revealed by this survey cannot be explained by the availability of different healthcare professionals nor by differences in healthcare expenditure, and such differences need further evaluation to determine their effect on outcomes and the economics of healthcare so that we may determine that which is optimal.

Modulation of the epithelial inflammatory response to rhinovirus in an atopic environment.

BACKGROUND: Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. OBJECTIVE: To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. METHODS: Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-beta1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. RESULTS: RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-beta1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the 'atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. CONCLUSIONS: Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.

Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.

BACKGROUND: Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. OBJECTIVE: To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. METHODS: BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. RESULTS: RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. CONCLUSION: HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.

Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results.

BACKGROUND: Rosacea is a common skin condition but the treatments currently available are not satisfactory. OBJECTIVES: To assess the efficacy of intense pulsed light (IPL) for treatment of stage I rosacea (flushing, erythema and telangiectasia). METHODS: Thirty-four patients were treated, 25 women and nine men, mean age 47 years. The treatment employed was IPL 515-1200 nm, with a 560 nm cut-off filter. The fluence range was 24-32 J cm(-2). Four treatments were administered on the face at 3-week intervals. Erythema values were measured at baseline and at the end of the treatment period on the cheeks and chin. Digital photographs were assessed by a consultant dermatologist on a 10-point visual analogue scale (VAS). Patients' assessments were also made using a 10-point VAS. Outcome measures were repeated 6 months after treatment. RESULTS: After four treatments the mean reduction of the erythema values was 39% on the cheeks (P < 0.001) and 22% on the chin (P < 0.001). This was confirmed by photographic assessment where erythema improved by 46% and telangiectasia by 55% (P < 0.001). The severity of rosacea was reduced on average by 3.5 points on the 10-point VAS. Patients' and physicians' assessments of the overall improvement of rosacea were similar: more than 50% improvement was noticed in 73% and 83% of patients, respectively (P < 0.001). The results were sustained at 6 months. Side-effects were minimal and self-limiting. CONCLUSIONS: IPL significantly reduces erythema and telangiectasia of rosacea and this is sustained for at least 6 months.

A Molecular Imaging "Skin A Time-resolving Intraoperative Imager for Microscopic Residual Cancer Detection Using Enhanced Upconverting Nanoparticles.

Optimal cancer therapy requires targeted and individualized treatment of all tumor cells, including both gross and microscopic disease. Intraoperatively hard to visualize and often left behind, microscopic foci of residual cancer cells significantly increase the risk of cancer recurrence and treatment failure rates. Fluorescently-tagged targeted molecular labels are employed to guide surgery, but conventional fluorescent intraoperative imagers suffer from lack of sensitivity and maneuverability, limiting practicality in small tumor cavities owing to their cumbersome sizes driven by optics. This work does away with conventional lenses and filters and introduces an optics-free molecular imaging "skin" consisting of only a $25\mu \mathrm{m}$ thin CMOS contact imager that synergistically integrates the long emission lifetimes of upconverting nanoparticles (UCNP) combined with upconversion to use a time domain approach to acquire the image coupled with infrared illumination allowing deep tissue penetration and elimination of autofluorescence. Using this strategy, we are able to visualize UCNPs at fluences (W/cm2) compatible with intraoperative use, opening the door to visualize targeted areas with microscopic sensitivity and facilitate residual microscopic disease detection during surgery, and laying the groundwork for precision post-operative radiation.

Plasma deoxyadenosine, adenosine, and erythrocyte deoxyATP are elevated at birth in an adenosine deaminase-deficient child.

We have determined concentrations of adenosine, deoxyadenosine, and deoxyATP (dATP) in cord blood from an infant prenatally diagnosed as ADA deficient. Plasma deoxyadenosine and adenosine were already elevated in cord blood (0.7 and 0.5 microM vs. normal of less than 0.07 microM). Elevation of plasma deoxyadenosine has not previously been documented in these children. Erythrocyte dATP content was also elevated at birth (215 nmol/ml packed erythrocytes vs. normal of 2.9). These elevated concentrations of adenosine, deoxyadenosine, and dATP are similar to those we observed in another older adenosine deaminase-deficient patient and may explain the impaired immune function and lymphopenia seen at birth.

Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radiofrequency lesion in patients with coronary artery disease.

BACKGROUND: A variety of mapping criteria have been proposed to localize critical sites at which radiofrequency (RF) can predictably terminate reentrant ventricular tachycardia (VT) caused by coronary artery disease. The purpose of this study was to determine the accuracy of using a combination of 3 mapping criteria in predicting termination of VT by a single RF lesion. METHODS AND RESULTS: Fifteen consecutive patients with coronary artery disease and recurrent sustained VT underwent an attempted RF ablation of 20 monomorphic VTs. Successful termination of VT by a single RF lesion was predicted if all the following mapping criteria were met: (1) an exact QRS match in the 12-lead ECG during entrainment; (2) a return cycle length

Different patterns of interatrial conduction in clockwise and counterclockwise atrial flutter.

BACKGROUND: The terms counterclockwise (CC) and clockwise (C) atrial flutter (Afl) are used to describe right atrial activation around the tricuspid valve in the left anterior oblique view. The manner in which the left atrium is activated, as reflected by coronary sinus (CS) recordings, has not been systematically evaluated. METHODS AND RESULTS: Nine patients with both CC and C Afl underwent electrophysiological study with CS recordings during both rhythms with the use of a decapolar catheter with the tip placed in the distal CS. Patterns of CS activation during each type of Afl as well as during during sinus rhythm were categorized into 1 of 3 patterns: sequential proximal-to-distal, sequential distal-to-proximal, and fused, indicating activation from different directions. In 7 of 9 patients, the pattern of CS activation in CC Afl and C Afl differed, with a proximal-to-distal pattern in CC Afl and a fused pattern in C Afl. In 2 patients, pacing the high right atrial septum near the presumed site of Bachmann's bundle in sinus rhythm showed a similar fused pattern of CS activation. CONCLUSIONS: These results demonstrate different patterns of CS activation in CC Afl and C Afl in the majority of patients and are consistent with a model in which the left atrium is activated predominantly over Bachmann's bundle during C Afl and over the CS os in CC Afl. These findings may have implications for maintenance of Afl, interpretation of flutter wave morphology on surface ECG, and left atrial mechanical function in Afl.

Incidence and predictors of myocardial infarction among patients with atrial fibrillation.

OBJECTIVES: We sought to evaluate the utility of excluding myocardial infarction (MI) in patients presenting to the emergency department (ED) with atrial fibrillation (AF) and to identify predictors of MI in this group. BACKGROUND: Patients with AF are frequently admitted to the hospital, in part, to exclude an associated MI. There are no prospective data on unselected patients to support this common practice. METHODS: We conducted a prospective cohort study of all patients who presented to a single-center ED with the primary diagnosis of AF. RESULTS: Of a total of 255 patients, 190 (75%) were admitted to the hospital, and 109 of them underwent a standard "rule-out MI" protocol. Of these 109 patients, six (5.5%) were identified as having an acute MI at the time of admission. Chest pain was present in 39% of patients, with a sensitivity and specificity for the occurrence of MI of 100% and 65%, respectively. ST segment elevation or depression was present in 43% of patients, with a sensitivity and specificity of 100% and 51%. The presence of either major ST segment depression (>2 mm) or elevation on the admission electrocardiogram (ECG) was present in 6%, with a sensitivity of 100% and a specificity of 99%. The resulting positive and negative predictive values were 86% (95% confidence interval [CI] 42% to 99%) and 100% (95% CI 96% to 100%), respectively. Use of this criterion would have reduced the number of rule-out MIs in our study group by 94%, with no loss of sensitivity. CONCLUSIONS: Chest pain and ST segment depression are extremely common findings in patients presenting to the ED with AF and have limited power to predict MI. In contrast, ECG evidence of ST segment elevation or depression >2 mm appears to be a reliable discriminator of which patients are at risk for MI. Patients without significant ST segment changes are at very low risk for MI and may not require performance of the rule-out MI protocol or hospital admission if clinically stable.

Pathophysiologic role of calcium in the development of vascular smooth muscle tone.

Recent information indicates that the intracellular ionized calcium concentration [Ca2+]i plays a regulatory role not only in determining the magnitude of vascular tone but also in regulating growth of vascular tissue. Studies on living vascular smooth muscle cells using the calcium indicator aequorin have revealed that the relation between [Ca2+]i and contraction of the vascular smooth muscle cell is complex. More than 1 intracellular kinase may be involved, leading to the coexistence of multiple excitation-contraction coupling pathways. However, it appears that all of these pathways may be calcium-dependent. It is not yet known whether the cause of human essential hypertension involves an elevated [Ca2+]i in the vascular smooth muscle cell. However, evidence is presented supporting the concept that a decreased [Ca2+]i in the hypertensive smooth muscle cell will lead to a decrease in vascular tone and total peripheral resistance, and possibly also antagonize the growth response of the vascular smooth muscle cell associated with the secondary effects of hypertension.

Presence and significance of the left atrionodal connection during atrioventricular nodal reentrant tachycardia.

It has been suggested that the anatomic substrates of dual atrioventricular nodal pathways are likely to be the atrionodal connections. During atrioventricular nodal re-entrant tachycardia (AVNRT) or ventricular pacing (VP), an earliest retrograde atrial activation in the coronary sinus (CS) distal to the ostium (CS breakthrough) would suggest the presence of an exit from a left atrionodal connection. The aim of the study was to evaluate the incidence of such an atrial retrograde activation in the CS during AVNRT and VP. The retrograde atrial activation was recorded during typical AVNRT (38 patients, 27 women, mean age 44 +/- 18 years) by a multipolar catheter in the CS, a decapolar catheter in the His bundle position, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the CS ostium. In 31 patients the retrograde atrial activation was recorded also during VP at a similar cycle length. A CS breakthrough was found in 18 patients during AVNRT (47%) and in 13 patients during VP (42%). Presence or absence of CS breakthrough was concordant between AVNRT and VP in 90% of the patients. A CS breakthrough, suggesting a left-sided atrionodal connection, is frequently recorded both during AVNRT and VP. In patients with a CS breakthrough pattern, the absence of correlation between the His bundle to the earliest CS retrograde atrial electrogram interval and AVNRT cycle length, or any other atrial activation times recorded in the posterior and anterior region of the Koch's triangle, would suggest that the left-sided atrionodal connection is a bystander during typical AVNRT.

Origin of junctional rhythm during radiofrequency ablation of atrioventricular nodal reentrant tachycardia in patients without structural heart disease.

Junctional rhythm is commonly observed during radiofrequency catheter ablation of the fast or slow pathways of atrioventricular nodal reentrant tachycardia (AVNRT). However, the origin of these beats remains unclear. We analyzed the retrograde atrial activation sequence of 16 patients (mean +/- SD: 41.2 +/- 18.9 years old) undergoing catheter ablation for typical AVNRT with detailed catheter mapping of the triangle of Koch. The earliest atrial activations were concordant during tachycardia and junctional rhythm in only 5 of 16 patients. The findings suggest that junctional rhythm is unlikely to represent direct stimulation of the atrioventricular (AV) node via a discrete slow pathway but rather results from enhanced automaticity from > or =1 sites in the AV nodal transitional zone. The ensuing atrial activation pattern results from anisotropic spread from these sites. In addition, these data imply that the original concept of the AV node comprising 2 anatomically defined pathways may not be valid, and that a functionally defined pathway model may be a more accurate representation.

Assessment of fetal anatomy in the first trimester using two- and three-dimensional ultrasound.

The objective of this study was to perform a complete anatomical survey of the fetus at 12-13 weeks gestation using stored volumes acquired by a three-dimensional (3D) scanner. 159 consecutive women at 12-13 weeks gestation who had a routine early pregnancy scan in our unit were recruited. A complete survey of the fetal anatomy was attempted by two-dimensional (2D) transabdominal and, if needed, transvaginal ultrasound. Then, using a 3D transvaginal probe, two volumes of the whole fetus were acquired. A complete anatomical survey (excluding anatomy of the heart) was attempted using the stored data. A complete anatomical survey was achieved in 93.7% (149) of cases with 2D ultrasound compared to 80.5% (128) of cases with 3D volume acquisition (p<0.001). The nuchal translucency was measured with 2D scanning in 98.7% of cases and in 91.8% of cases using 3D volumes. The mean time to perform a 2D scan was 12.2 min standard deviation (SD 3.4 min) while the mean time to obtain and examine the stored volumes was 8.4 min (SD 1.45 min, p<0.001). Real-time 2D ultrasound is still the best way to examine fetal anatomy in the first trimester. However, 3D ultrasound can be a useful addition to clinical practice, providing views not easily obtained by conventional 2D ultrasound. It can potentially minimize actual scanning time and provides an excellent way to store scanned data.

The use of three-dimensional ultrasound for fetal gender determination in the first trimester.

The objective of this study was to examine the accuracy of fetal gender prediction at a routine first trimester scan using three-dimensional (3D) ultrasound. 200 women were recruited for this study and they agreed to have a transvaginal scan for their routine first trimester scan for fetal anatomy and nuchal thickness measurement. 3D volumes were obtained and stored. Two examiners independently reviewed all the volumes and recorded their diagnosis of fetal gender and measured the angle between the genital tubercle and the skin overlying the sacrum. After studying the 3D volumes both examiners recorded a diagnosis of male or female in 150 cases (81.5%). In 34 cases (18.5%) either both (n=21) or one of them (n=13) could not comment on fetal gender by studying the saved volume. From these 150 cases correct prediction of fetal gender by both examiners was achieved in 85.3% of cases. In 6.7% of cases both examiners predicted the wrong gender while for the rest 8% of cases each examiner assigned different gender to the fetus (k=0.84; standard error 0.045). Angle measurements performed from the saved 3D volumes were highly reproducible. Gestational age did not affect the accuracy of gender identification. This study demonstrates that 3D ultrasound can be an effective and fast way of identifying fetal gender in the first trimester. The advantages of 3D ultrasound stem from its ability to virtually reproduce all required views.

Particularities of pollen allergies in Greece.

Pollen allergy is a significant clinical problem in older Greek children causing approximately 25% of respiratory allergic disease in children of mean age 10 years. This is due to climatic conditions that favor rich and long pollinic seasons more so in Central and Southern Greece as well as the Greek islands. Similarities are evident between Greece and other Mediterranean countries, especially Southern Italy and Spain. Most prevalent allergenic plants with known clinical significance are grasses, Olea europaea and Parietaria species. The pollen grains of these plants can reach high atmospheric concentrations if the weather conditions are favorable, causing severe clinical symptoms of rhinoconjunctivitis and/or asthma. Preseasonal and coseasonal drug administration as well as immunotherapy are used in the management of children with pollinosis. More aerobiologic and allergen identification studies at a local level are needed to fully evaluate the type and specific characteristics of pollen allergens in Greece. Furthermore, additional epidemiologic studies in children are necessary to fully appreciate the magnitude of the problem and the natural outcome.