Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid-organ transplant recipients with cytomegalovirus disease.

BACKGROUND:It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease. METHODS:Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy). RESULTS:Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipient-seropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; P = .001). Median baseline viral loads were higher and time to viral eradication was longer ( P = .006 and P = .026 , respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007 ) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence. CONCLUSIONS:No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.

Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs

Rapport de synthèse : Contexte: l'hydroxyéthylamidon (HEA) est largement utilisé comme expanseur volémique en anesthésiologie et réanimation. Cependant, cette classe de produits perturbe le system de la coagulation. Des améliorations restent possibles dans le choix de la combinaison optimale de poids moléculaire, de degré de substitution en radicaux éthyle et de localisation de ces radicaux sur le squelette glucidique des polymères, afin d'optimiser leur efficacité et leur tolérance. L'HEA de poids moléculaire élevé et faiblement substitué n'affecte pas plus la coagulation sanguine que de l'HEA de bas poids moléculaire faiblement substitué. Nous examinons in vivo l'effet d'un abaissement du rapport C2/C6 sur les caractéristiques pharmacocinétiques et l'impact sur la coagulation sanguine d'un HEA de haut poids moléculaire faiblement substitué. Matériels et méthode: nous comparons dans une étude prospective, randomisée et parallèle l'HEA 650/0.42/2.8 avec l'HEA 650/0.42/5.6 auprès de 30 cochons. Avant, pendant et jusqu'à 630 minutes après une perfusion de 30 ml/kg d'HEA, des échantillons sanguins ont été collectés pour mesurer les concentrations d'HEA, les tests de coagulation plasmatique classiques et la coagulation sanguine par thrombélastographie (TEG®, Haemoscope Corporation, Niles, II, U.S.). Les paramètres pharmacocinétiques ont été estimés en adaptant un modèle à deux compartiments. Résultats: la constante d'élimination est de 0.009 ± 0.001 (min-1) pour l'HEA 650/0.42/2.8 et 0.007 ± 0.001 (min-1) pour l'HEA 650/0.42/5.6 (p<0.001); la surface sous la courbe de concentration est de 1374 ± 340 min*g/L pour l'HEA 650/0.42/2.8 et 1697 ± 411 min*g/L pour l'HEA 650/0.42/5.6 (p=0.026). Les concentrations mesurées d'HEA ne montrent pas de différence entre l'HEA 650/0.42/2.8 et l'HEA 650/0.42/5.6. Les deux solutions d'HEA affectent de façon identique la coagulation sanguine: l'index de coagulation thrombélastographique diminue pareillement à ta fin de la perfusion d'HEA 650/0.42/2.8 et d'HEA 650/0.42/5.6 (p=0.29). De même, le temps de thromboplastine partielle activée et le temps de prothrombine augmentent de manière similaire pour l'HEA 650/0.42/2.8 et l'HEA 650/0.42/5.6 (p=0.83). Conclusion: la réduction du rapport C2/C6 de l'HEA de poids moléculaire élevé et faiblement substitué aboutit à une élimination légèrement accélérée d'HEA. Cependant, elle ne modifie pas l'effet perturbateur sur la coagulation.

The clinical and biological impact of new pathogen inactivation technologies on platelet concentrates.

Since 1990, several techniques have been developed to photochemically inactivate pathogens in platelet concentrates, potentially leading to safer transfusion therapy. The three most common methods are amotosalen/UVA (INTERCEPT Blood System), riboflavin/UVA-UVB (MIRASOL PRT), and UVC (Theraflex-UV). We review the biology of pathogen inactivation methods, present their efficacy in reducing pathogens, discuss their impact on the functional aspects of treated platelets, and review clinical studies showing the clinical efficiency of the pathogen inactivation methods and their possible toxicity.

Treatment of congenital aortic valve stenosis: impact of the Ross operation.

GOAL: To evaluate the impact of the Ross operation, recently (1997) introduced in our unit, for the treatment of patients with congenital aortic valve stenosis. METHODS: The period from January 1997 to December 2000 was compared with the previous 5 years (1992-96). Thirty-seven children (< 16 yrs) and 49 young adults (16-50 yrs) with congenital aortic valve stenosis underwent one of these treatments: percutaneous balloon dilatation (PBD), aortic valve commissurotomy, aortic valve replacement and the Ross operation. The Ross operation was performed in 16 patients, mean age 24.5 yrs (range 9-46 yrs) with a bicuspid stenotic aortic valve, 7/10 adults with calcifications, 2/10 adults with previous aortic valve commissurotomy, 4/6 children with aortic regurgitation following PBD, and 1/6 children who had had a previous aortic valve replacement with a prosthetic valve and aortic root enlargement. RESULTS: PBD was followed by death in two neonates (fibroelastosis); all other children survived PBD. Although there were no deaths, PBD in adults was recently abandoned, owing to unfavourable results. Aortic valve commissurotomy showed good results in children (no deaths). Aortic valve replacement, although associated with good results (no deaths), has been recently abandoned in children in favour of the Ross operation. Over a mean follow-up of 16 months (2-40 months) all patients are asymptomatic following Ross operation, with no echocardiographic evidence of aortic valve regurgitation in 10/16 patients and with trivial regurgitation in 6/16 patients. CONCLUSIONS: The approach now for children and young adults with congenital aortic valve stenosis should be as follows: (1) PBD is the first choice in neonates and infants; (2) Aortic valve commissurotomy is the first choice for children, neonates and infants after failed PBD; (3) The Ross operation is increasingly used in children after failed PBD and in young adults, even with a calcified aortic valve.

A concentric analysis of the impact of urbanization on the threatened European tree frog in an agricultural landscape

Pond-breeding amphibians are affected by site-specific factors and regional and landscape-scale patterns of land use. Recent anthropogenic landscape modifications (drainage, agriculture intensification, larger road networks, and increased traffic) affect species by reducing the suitable habitat area and fragmenting remaining populations. Using a robust concentric approach based on permutation tests, we evaluated the impact of recent landscape changes on the presence of the endangered European tree frog (Hyla arborea.) in wetlands. We analyzed the frequency of 1 traffic and 14 land-use indices at 20 circular ranges (from 100-m up to 2-km radii) around 76 ponds identified in western Switzerland. Urban areas and road surfaces had a strong adverse effect on tree frog presence even at relatively great distances (from 100 m up to 1 km). When traffic measurements were considered instead of road surfaces, the effect increased, suggesting a negative impact due to a vehicle-induced effect. Altogether, our results indicate that urbanization and traffic must be taken into account when pond creation is an option in conservation management plans, as is the case for the European tree frog in western Switzerland. We conclude that our easy-to-use and robust concentric method of analysis can successfully assist managers in identifying potential sites for pond creation, where probability of the presence of tree frogs is maximized.

Impact of preoperative central neurologic dysfunction on patients undergoing emergency surgery for type a dissection.

BACKGROUND: Preoperative central neurologic deficits in the context of acute type A dissection are a complex comorbidity and difficult to handle. The aim this study was to analyze this subgroup of patients by comparing them with neurologically asymptomatic patients with type A dissection. Results may help the surgeon in preoperative risk assessment and thereby aid in the decision-making process. METHODS: We reviewed the data of patients admitted for acute type A dissection during the period from 1999 to 2010. Associated risk factors, time to surgery from admission, extension of the dissection, localization of central nervous ischemic lesions, and the influence of perioperative brain protective strategies were analyzed in a comparison of preoperative neurologically deficient to nondeficient patients. RESULTS: Forty-seven (24.5%) of a total of 192 patients had new-onset central neurologic symptoms prior to surgery. Concomitant myocardial infarction (OR 4.9, 95% CI 1.6-15.3, P = 0.006), renal failure (OR 5.9, 95% CI 1.1-32.8, P = 0.04), dissected carotid arteries (OR 9.2, 95% CI 2.4-34.7, P = 0.001), and late admission to surgery at >6 hours after symptom onset (OR 2.7, 95% CI 1.1-6.8, P = 0.04) were observed more frequently in neurologically deficient patients. These patients had a higher 30-day in-hospital mortality on univariate analysis (P = 0.01) and a higher rate of new postoperative neurologic deficits (OR 9.2, 95% CI 2.4-34.7, P = 0.02). Neurologic survivors had an equal hospital stay, and 67% of them had improved symptoms. CONCLUSIONS: The predominance of neurologic symptoms at admission may be responsible for an initial misdiagnosis. The concurrent central nervous system ischemia and myocardial infarction explains a higher mortality rate and a more extensive "character" of the disease. Neurologically deficient patients are at higher risk of developing new postoperative neurologic symptoms, but prognosis for the neurologic evolution of survivors is generally favorable.

The impact of carotid plaque screening on motivation for smoking cessation.

Showing smokers their own atherosclerotic plaques might increase motivation for smoking cessation, since they underestimate their own risk for smoking-related diseases. To assess the feasibility and optimal processes of studying the impact of carotid atherosclerotic plaque screening in smokers, we enrolled 30 daily cigarette smokers, aged 40-70 years, in an observational pre-post pilot study. All smokers underwent smoking cessation counseling, nicotine replacement therapy, a carotid ultrasound, an educational tutorial on atherosclerosis, baseline and 2-month motivation to change assessment, and assessment of smoking cessation at 2 months. Participants had a mean smoking duration of 34 years (SD = 7). Carotid plaques were present in 22 smokers (73%). Between baseline and 2 months after plaque screening, motivation for smoking cessation increased from 7.4 to 8.4 out of 10 (p = .02), particularly in those with plaques (7.2 to 8.7, p = .008). At 2 months, the smoking quit rate was 63%, with a quit rate of 73% in those with plaques vs. 38% in those without plaques (p = .10). Perceived stress, anxiety, and depression did not increase after screening. 96% of respondents answered correctly at least 80% of questions regarding atherosclerosis knowledge at baseline and after 2 months. In conclusion, studying the process of screening for carotid plaques for the purpose of increasing motivation for smoking cessation, in addition to counseling and drug therapy for smoking cessation in long-term smokers, appears feasible. The impact of carotid plaque screening on smoking cessation should be examined in larger randomized controlled trials with sufficient power to assess the impact on long-term smoking cessation rates.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Transitions in social complexity along elevational gradients reveal a combined impact of season length and development time on social evolution.

Eusociality is taxonomically rare, yet associated with great ecological success. Surprisingly, studies of environmental conditions favouring eusociality are often contradictory. Harsh conditions associated with increasing altitude and latitude seem to favour increased sociality in bumblebees and ants, but the reverse pattern is found in halictid bees and polistine wasps. Here, we compare the life histories and distributions of populations of 176 species of Hymenoptera from the Swiss Alps. We show that differences in altitudinal distributions and development times among social forms can explain these contrasting patterns: highly social taxa develop more quickly than intermediate social taxa, and are thus able to complete the reproductive cycle in shorter seasons at higher elevations. This dual impact of altitude and development time on sociality illustrates that ecological constraints can elicit dynamic shifts in behaviour, and helps explain the complex distribution of sociality across ecological gradients.

Impact of voting advice applications on voters's decision-making

So-called online Voting Advice Applications (VAAs) have become very popular all over Europe. Millions of voters are using them as an assistance to make up their minds for which party they should vote. Despite this popularity there are only very few studies about the impact of these tools on individual electoral choice. On the basis of the Swiss VAA smartvote we present some first findings about the question whether VAAs do have a direct impact on the actual vote of their users. In deed, we find strong evidence that Swiss voters were affected by smartvote. However, our findings are somewhat contrary to the results of previous studies from other countries. Furthermore, the quality of available data for such studies needs to be improved. Future studies should pay attention to both: the improvement of the available data, as well as the explanation of the large variance of findings between the specific European countries.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania.

OBJECTIVE: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. METHODS: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.

Impact of clinical practice guidelines on priorisation for intensive care beds allocation in high-risk acute coronary syndrome patients: does age play a role?

QUESTION UNDER STUDY: To assess which high-risk acute coronary syndrome (ACS) patient characteristics played a role in prioritising access to intensive care unit (ICU), and whether introducing clinical practice guidelines (CPG) explicitly stating ICU admission criteria altered this practice. PATIENTS AND METHODS: All consecutive patients with ACS admitted to our medical emergency centre over 3 months before and after CPG implementation were prospectively assessed. The impact of demographic and clinical characteristics (age, gender, cardiovascular risk factors, and clinical parameters upon admission) on ICU hospitalisation of high-risk patients (defined as retrosternal pain of prolonged duration with ECG changes and/or positive troponin blood level) was studied by logistic regression. RESULTS: Before and after CPG implementation, 328 and 364 patients, respectively, were assessed for suspicion of ACS. Before CPG implementation, 36 of the 81 high-risk patients (44.4%) were admitted to ICU. After CPG implementation, 35 of the 90 high-risk patients (38.9%) were admitted to ICU. Male patients were more frequently admitted to ICU before CPG implementation (OR=7.45, 95% CI 2.10-26.44), but not after (OR=0.73, 95% CI 0.20-2.66). Age played a significant role in both periods (OR=1.57, 95% CI 1.24-1.99), both young and advanced ages significantly reducing ICU admission, but to a lesser extent after CPG implementation. CONCLUSION: Prioritisation of access to ICU for high-risk ACS patients was age-dependent, but focused on the cardiovascular risk factor profile. CPG implementation explicitly stating ICU admission criteria decreased discrimination against women, but other factors are likely to play a role in bed allocation.

Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden.

A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.