Out-of-hospital resuscitation in Estonia: a bystander-witnessed sudden cardiac arrest.

OBJECTIVE: To evaluate the results of the first epidemiological study on out-of-hospital resuscitation in Estonia. METHODS: A prospective cohort study of 2108 consecutive standardized reports on out-of-hospital resuscitation attempts from 1 January 1999 to 31 December 2002 was conducted according to the Utstein style. RESULTS: In all, 67.3% (1419/2108) of the cardiac arrests were of presumed cardiac aetiology and 60.2% (854/1419) of them were bystander-witnessed. Of these, the 28% bystander cardiopulmonary resuscitation was initiated, and the first rhythm was recorded as ventricular fibrillation or pulseless ventricular tachycardia in 40% of the cases. In the subgroup of patients with bystander-witnessed cardiac arrest of cardiac origin, 10.7% (91/854) were discharged alive in good cerebral performance categories and 7.7% were alive at the 1-year follow-up. The chances of survival increased if the median response time interval was <6 min, cardiac arrest occurred in a public place, patients received bystander cardiopulmonary resuscitation and had an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia. The discharge rate was 24% (82/343) in the subgroup of patients who had bystander-witnessed cardiac arrest of cardiac origin and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia. In this subgroup, the survival rate was 42.6% (40/94) in Tartu urban area, 16.9% (22/130) in Tallinn urban area and 16.8% (20/119) in other regions of Estonia (mostly urban and suburban areas). CONCLUSION: The results demonstrate that despite the progress in the management of out-of-hospital cardiac arrest in Estonia, only one centre (Tartu) achieves a better survival rate. Further improvements are needed to raise the quality of the Estonian emergency medical services system, especially in rural areas.     

The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments

Dendritic cells (DCs) need to migrate in the interstitial environment of peripheral tissues to reach secondary lymphoid organs and initiate a suitable immune response. Whether and how inflamed tissues instruct DCs to emigrate is not fully understood. In this study, we report the unexpected finding that the epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human DCs in a cell-autonomous manner. TSLP induced the polarization of both microtubule and actin cytoskeletons and promoted DC 3-dimensional migration in transwell as well as in microfabricated channels that mimic the confined environment of peripheral tissues. TSLP-induced migration relied on the actin-based motor myosin II and was inhibited by blebbistatin. Accordingly, TSLP triggered the redistribution of phosphorylated myosin II regulatory light chain to the actin cortex, indicating that TSLP induces DC migration by promoting actomyosin contractility. Thus, TSLP produced by epithelial cells in inflamed tissue has a critical function in licensing DCs for cell-autonomous migration. This indicates that cytokines can directly trigger cell migration, which has important implications in immune physiopathology and vaccine design.     

A controlled study of mianserin in moderately to severely depressed outpatients

Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.     

TSLP: from allergy to vaccine adjuvant

The field of vaccine adjuvants has been an area of active research and development because of the need to improve the generation of protective immunity to a large number of pathogens, as well as in diseases such as cancer. Adjuvants can also help induce stronger immune responses with fewer injections, and consequently improve both the feasibility and success rate of large-scale population vaccine campaigns in developing countries. A current challenge is to identify vaccine adjuvants of various classes (cytokines, toll-like receptor ligands, etc.) with specific immune-modulating properties in order to tailor the immune response to certain pathological situations. In this issue, Van Roey et al. [Eur. J. Immunol. 2012. 42: 353-363] explore one of these challenges, namely to identify novel mucosal adjuvants. Van Roey et al. show that the pro-allergic cytokine thymic stromal lymphopoietin (TSLP) promotes a strong B-cell response with production of secretory IgA at mucosal sites. Here, we discuss the importance and limits of these findings within the broader field of vaccine adjuvants, and the potential development of TSLP as a mucosal and B-cell adjuvant in humans.     

Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia

Two randomized, double-blind, 26-week core studies (Eastern [EH] and Western Hemisphere [WH]) tested the hypothesis that asenapine is superior to olanzapine for persistent negative symptoms of schizophrenia; 26-week extension studies assessed the comparative long-term efficacy and safety of these agents. In the core studies, 949 people were randomized to asenapine (n = 241 and 244) or olanzapine (n = 240 and 224); 26-week completion rates with asenapine were 64.7% and 49.6% (olanzapine, 80.4% and 63.8%) in the EH and WH, respectively. In the EH and WH extensions, respectively (asenapine, n = 134 and 86; olanzapine, n = 172 and 110), 52-week completion rates were 84.3% and 66.3% with asenapine (olanzapine, 89.0% and 80.9%). Asenapine was not superior to olanzapine in change in the 16-item Negative Symptom Assessment Scale total score in either core study, but asenapine was superior to olanzapine at week 52 in the WH extension study. Olanzapine was associated with modest, but significantly greater, changes in PANSS positive subscale score at various assessment times in both core studies and the WH extension study. Incidence of treatment-emergent adverse events was comparable between treatments across studies. Weight gain was consistently lower with asenapine. Extrapyramidal symptom-related adverse event incidence was higher with asenapine (EH: 8.3%; 95% confidence interval [CI], 5.1%-12.5%; WH: 16.4%; 95% CI, 11.9%-21.6%) than olanzapine (EH: 3.3%; 95% CI, 1.4%-6.4%; WH: 12.1%; 95% CI, 8.1%-17.0%), but Extrapyramidal Symptom Rating Scale-Abbreviated total score changes did not significantly differ between treatments. In conclusion, asenapine superiority over olanzapine was not observed in the core studies. Both treatments improved persistent negative symptoms, but discontinuation rates were higher with asenapine.     

Detection and surveillance of left atrial thrombosis by transesophageal echocardiography

Out of 1,141 successive transoesophageal echocardiographic studies performed prospectively between 01/05/1993 and 31/12/1995, 26 cases of left atrial thrombosis were observed (2.2%); 5 were in the left atrium (20%), 19 in the left atrial appendage (73%) and the thrombi were in both atrium and left atrial appendage in 2 cases (7%). The 26 patients included 15 women and 11 men, with an average age of 69 +/- 16 years (range 25-89 years); 22 patients (84%) had permanent atrial fibrillation and 4 were in sinus rhythm. Only 5 of the patients were on oral anticoagulant therapy. All had underlying cardiac disease: 11 mitral valve diseases; 10 dilated cardiomyopathies; 2 hypertrophic cardiomyopathies; 3 other cardiac diseases. The indication for transoesophageal echocardiography was systemic embolism in 13 cases (50%); before D.C. cardioversion in 10 cases (38%) and before percutaneous mitral valvuloplasty in 3 cases. The thrombus was adherent in 18 cases (69%) and mobile in 8 cases (31%). Spontaneous contrast was observed in 23 cases (88%). Intravenous heparin was given as soon as the diagnosis was made. In 4 patients, thrombectomy was indicated in view of the threatening nature of the thrombus and/or the necessity for associated valve replacement. In 22 patients, heparin was relayed by oral anticoagulants on the 10th day of treatment. Control transoesophageal echocardiography was not performed because of the patient's refusal or poor general condition. The other 15 patients were reexamined 1 to 5 times between the 4th day and 12th month: a regression was observed in 13 cases (86%) which was complete in 11 and partial in 2 cases. No cases of embolism occurred during follow-up but six patients died: 1 of the operated cases and 5 of the patients treated medically (3 cardiac failures and 2 cerebral haemorrhages). The authors conclude that left atrial thrombosis is rare in the absence of classical embolic cardiac disease. With the exception of the surgical indication of a life-threatening thrombus and/or associated surgical mitral valve disease, anticoagulant therapy results in complete or partial regression of the thrombus visualised by transoesophageal echocardiography which is essential for follow-up. The prognosis depends on the severity of the underlying heart disease.