bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards the harmonization of outcome measures in children with mitochondrial disorders
Authors: Koene Saskia , Jansen Merel , Verhaak Chris M , De Vrueh Remco LA , De Groot Imelda JM , Smeitink Jan AM 
Published: March 2013

AimA clinical trial is only as reliable as its outcomes, therefore the careful and systematic selection of outcome measures is extremely important. Currently, the selection of outcome measures for clinical trials designed to evaluate new drugs in patients with mitochondrial disorders is inefficient and has not been addressed systematically. Given that meaningful data can be obtained only from trials in which outcomes are assessed using valid instruments, one should first focus on the validation of a set of selected instruments in the target population. The aim of this review is to systematically select a ‘toolbox’ of robust outcome measures that are relevant to all patients.MethodUsing an extensive search of published literature, we systematically compiled a toolbox with outcome measures based on a primary search for possible instruments Subsequently, we reduced this toolbox using strict criteria that were adapted from the United States Food and Drug Administration.ResultsA toolbox with clinically relevant and psychometrically robust instruments for performing clinical research in children with mitochondrial disorders was compiled.InterpretationIn coming years, more experience using these outcome measures in children with various mitochondrial disease phenotypes must be obtained before reliable conclusions regarding the validity of these instruments can be drawn.
Cardiovascular safety of the dipetidyl peptidase‐4 inhibitor alogliptin in type 2 diabetes mellitus
Authors: White W. B. , Pratley R. , Fleck P. , Munsaka M. , Hisada M. , Wilson C. , Menon V. 
Published: March 2013

AimAs there have been concerns that some classes or agents for the treatment of type 2 diabetes may increase CV risk, we evaluated the cardiovascular profile of the dipeptidyl peptidase‐4 inhibitor alogliptin.MethodsWe evaluated the incidence of CV events in patients treated with alogliptin, placebo or comparator antihyperglycaemic drugs in the clinical trial database for alogliptin using the composite major adverse cardiovascular event (MACE) endpoints of CV death, non‐fatal myocardial infarction and non‐fatal stroke.ResultsThe pooled analysis included 4168 patients exposed to alogliptin 12.5 and 25 mg daily for 2023 patient‐years compared to 691 patients treated with placebo for 263 patient‐years and 1169 patients treated with other antidiabetic agents (metformin, sulfonylureas and thiazolidinediones) for 703 patient‐years. CV events were adjudicated by an expert endpoint committee blinded to treatment allocation. The incidence rates of the combined MACE were not significantly different between patients treated with alogliptin and comparator therapies (hazard ratio=0.635, 95% confidence interval, 0.0, 1.41). Additionally, other types of serious CV events were not significantly different between patients treated with alogliptin and comparator therapies.ConclusionThese analyses have not shown a signal of increased CV risk with alogliptin in patients with type 2 diabetes. Future results from the adequately powered EXAMINE trial will definitively assess the CV safety profile of aloglipin in patients with type 2 diabetes mellitus.
Independent Role of Left Ventricular Global Longitudinal Strain in Predicting Prognosis of Chronic Heart Failure Patients
Authors: Iacoviello Massimo , Puzzovivo Agata , Guida Pietro , Forleo Cinzia , Monitillo Francesco , Catanzaro Raffaella , Lattarulo Maria Silvia , Antoncecchi Valeria , Favale Stefano 
Published: March 2013

AimsTo evaluate the independent prognostic role of two‐dimensional (2D) strain measures reflecting global longitudinal left ventricular (LV) systolic function in outpatients affected by chronic heart failure (CHF).Methods and resultsGlobal longitudinal LV systolic strain (GLS) was assessed in 308 outpatients affected by CHF, by analyzing standard views with 2D speckle tracking technique. During a mean follow‐up of 26 ± 13 months 37 patients died (29 due to cardiovascular causes), 10 patients underwent heart transplantation, and 75 patients experienced at least 1 episode of hospitalization due to acute decompensated heart failure (ADHF). Thirty‐one patients without a history of major ventricular arrhythmic events experienced the occurrence of ventricular fibrillation and/or tachycardia or sudden death was observed. Multivariate Cox regression analysis showed that GLS was significantly associated with all‐cause mortality (HR: 1.15; 95%CI: 1.02–1.30; P: 0.026), cardiovascular death (HR: 1.20; 95%CI: 1.04–1.39; P: 0.011), cardiovascular death or heart transplantation (HR: 1.24; 95%CI: 1.09–1.41; P: 0.001), ADHF‐related hospitalizations (HR: 1.15; 95%CI: 1.05–1.25; P: 0.003), and arrhythmic events (HR: 1.17; 95%CI: 1.03–1.33; P: 0.018).ConclusionsQuantifying LV longitudinal systolic function in CHF outpatients on the basis of 2D speckle tracking analysis provides a new parameter that independently predicts patient outcome, thus, strengthening its possible role in current clinical practice.
Left Ventricular Dyssynchrony Predicts Clinical Response to CRT – A Long‐Term Follow‐Up Single‐Center Prospective Observational Cohort Study
Authors: Prinz Christian , Lehmann Roman , Schwarz Maria , Prinz Eva‐Maria , Bitter Thomas , Vogt Jürgen , van Buuren Frank , Bogunovic Nikola , Lamp Barbara , Horstkotte Dieter , Faber Lothar 
Published: March 2013

BackgroundUntil now, there is no consensus regarding the definition of a clinical response to cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF) and systolic left ventricular (LV) dysfunction. The aim of this study was to evaluate if echocardiography is predictive for an objective improvement in exercise capacity during long‐term follow‐up of CRT.MethodsEach patient underwent echocardiography and spiroergometry both at baseline and at last follow‐up. Left ventricular dyssynchrony (LVD) before CRT was defined by tissue Doppler imaging (TDI) as intra‐LV delay ≥40 msec (septal‐lateral or anterior‐posterior). Clinical response to CRT was defined as increase of peakVO2 or as increase of maximal workload >10% as compared to baseline.ResultsMean follow‐up was 69 ± 37 months. From the 238 consecutive patients included in the study, 141 (59%) were classified as clinical responders and 97 (41%) as nonresponders. Baseline data of responders and nonresponders were comparable. However, clinical responders showed more often LVD (64%) than nonresponders (42%, P = 0.004). On multivariate regression analysis, nonischemic origin of CHF (β‐coefficient in the final model 0.1, P = 0.04) and LVD at baseline (β‐coefficient in the final model 0.2, P < 0.001) were independently associated with clinical response during long‐term follow‐up. Patients with LVD at baseline had significant more often an improvement of left ventricular ejection fraction >10% (P = 0.02) and a reduction of left ventricular end‐diastolic diameter (LVEDD) >10% (P < 0.01) than patients without LVD at baseline.ConclusionsLVD at baseline as assessed by a straightforward echocardiographic approach predicts the long‐term clinical response to CRT and is associated with a more pronounced reverse LV remodeling.
Patients With Severe Aortic Stenosis and Reduced Ejection Fraction: Earlier Recovery of Left Ventricular Systolic Function After Transcatheter Aortic Valve Implantation Compared With Surgical Valve Replacement
Authors: Bauer Fabrice , Coutant Véronique , Bernard Mathieu , Stepowski Dimitri , Tron Christophe , Cribier Alain , Bessou Jean‐Paul , Eltchaninoff Hélène 
Published: March 2013

BackgroundOnly 50% of patients with aortic stenosis (AS) and low ejection fraction (EF) improve their contractility after surgical aortic valve replacement (AVR). Long‐term prognosis of these patients is strongly correlated to EF recovery after the surgery. The aim of this study was to compare the postoperative left ventricular function recovery in patients with severe AS and reduced EF after AVR and transcatheter aortic valve implantation (TAVI).Methods and ResultsTwenty‐one patients undergoing AVR for severe AS (<1 cm²) and reduced EF (<45%) were echocardiographically compared with 31 patients treated with TAVI by conventional and two‐dimensional (2D) strain method. TAVI patients were older (83 ± 6 vs. 74 ± 13 years, P < 0.001), had more comorbidities (Euroscore 26 ± 15% vs. 16 ± 12%, P < 0.001) and no differences in ischemic heart disease (16.1% vs. 9.5%, P = 0.39). EF was similar in both groups at baseline. Aortic valve area significantly increased (P = 0.01) while pressure gradient decreased (P = 0.009) after both procedures but TAVI was associated with a better EF recovery compared with AVR at day 7. Regional function assessed by radial 2D strain increased in TAVI group but was transiently deteriorated in AVR patients (P < 0.05). Longitudinal as well as circumferential 2D strain progressively increased at follow‐up in both groups (P < 0.05). EF was similar in both groups at 3‐month follow‐up.ConclusionIn patients with severe AS and reduced EF, TAVI is associated with faster and better recovery of LV function compared with AVR.
The Diagnostic Utility of Transthoracic Echocardiography for the Diagnosis of Infective Endocarditis in the Real World of the Italian Registry on Infective Endocarditis
Authors: Cecchi Enrico , Chirillo Fabio , Faggiano Pompilio , Imazio Massimo , Cecconi Moreno , Moreo Antonella , Cialfi Alessandro , Rinaldi Mauro , Ponte Stefano Del , Squeri Angelo , Gaddi Oscar , Enia Francesco , Ferro Silvia , Costanzo Piera , Zuppiroli Alfredo , Bergandi Gianluigi , Bologna Flavio , Ciampani Nino , De Rosa Francescogiuseppe , Belli Riccardo ,   for the Italian Registry on Infective Endocarditis (RIEI) Investigators
Published: March 2013

BackgroundThe choice of the imaging modality (transthoracic [TTE] vs. transesophageal echocardiography [TEE]) for the diagnosis of infective endocarditis (IE) depends on different variables. Aim of the present study is to provide updated data on the diagnostic sensitivity and the clinical usefulness of TTE vs. TEE from the Italian Registry on IE (RIEI).MethodsThe RIEI has enrolled consecutive cases of IE in every participating centre, evaluating diagnostic and therapeutic data from a real world practice perspective.ResultsFrom July 2007 to October 2010, 658 consecutive cases with definite IE according to Duke criteria have been enrolled in the RIEI (483 males). The following diagnostic echocardiographic exams were performed: 616 TTE (94%) and 476 TEE (72%). A positive TTE was recorded in 399 cases (65%), an uncertain TTE in 108 cases (17%), and a negative TTE in 109 cases (18%). For TEE, a positive study was reported in 451 cases (95%), uncertain in 13 cases (2.7%), and negative in 12 cases (2.5%) (P < 0.001). This difference is not evident in patients with tricuspid valve IE or i.v. drug addiction, and in Streptococcus bovis or Streptococcus viridans IE. TTE was significantly more performed before the admission and earlier than TEE during admission (P = 0.000). TTE was mainly responsible for the initial diagnosis in 59%. TEE contributed to changing the therapeutic approach in 42%.ConclusionsIn the real world, TTE is performed earlier and more commonly, and it is the major echocardiographic tool for the initial diagnosis. TEE confirms its superior diagnostic sensitivity in most cases, although it is relatively underused.
Insight and suicidality in first‐episode psychosis: understanding the influence of suicidal history on insight dimensions at first presentation
Authors: López‐Moríñigo Javier D. , Wiffen Benjamin , O'Connor Jennifer , Dutta Rina , Di Forti Marta , Murray Robin M. , David Anthony S. 
Published: March 2013

AbstractAimLack of insight is a cardinal feature of psychosis with crucial implications for outcome. Concerns have been raised regarding a link between insight and suicidality. This study aimed to test the relationship between suicidal behaviour preceding first‐episode psychosis (FEP) and insight dimensions at treatment onset.MethodsA total of 112 FEP inpatients were recruited. Suicidal events prior to admission were recorded. Insight was assessed multidimensionally with the Schedule for the Assessment of Insight – Expanded version shortly after admission. Suicidal and non‐suicidal patients were compared regarding scores on ‘total insight’ and three insight domains: ‘awareness of mental illness’, ‘relabeling of psychotic experiences as abnormal’ and ‘compliance’. This analysis was also adjusted for a set of sociodemographic, clinical, neurocognitive and psychopathological variables.ResultsBivariate analyses demonstrated a direct association between previous suicidality and all insight domains. However, these associations did not survive multivariable regression models, which demonstrated gender (female), shorter duration of untreated psychosis (DUP) and psychopathological symptoms – depression and disorganization – to mediate the influence of suicidal history on insight, and therefore to underlie the latter.ConclusionsInsight dimensions in FEP patients are influenced by having suicidal antecedents through some mediating variables such as gender, DUP and depression. Further prospective studies are needed to clarify the potential implications of these findings on the management of insight in FEP. As suicidal history is associated with greater levels of both depression and insight at first presentation, these three variables might be useful in predicting further suicidal events.
Improving vocational outcomes of service users in an Early Intervention in Psychosis service
Authors: Dudley Robert , Nicholson Marsha , Stott Pauline , Spoors George 
Published: March 2013

AbstractAimPeople with psychotic symptoms have poor social and occupational functioning. The aim of this research was to improve the engagement in meaningful education, training or employment for young people with psychosis. This was undertaken by introducing a vocational specialist into the early intervention service to implement the individual placement and support (IPS) model.MethodsTwo early intervention services provided information about the vocational status of their service users 6 and 1 months prior to the introduction of the vocational specialist into one of the services. Data were collected again 12 months following the intervention and then 6 months following the end of the intervention.ResultsUnemployment was high in both services during the baseline period (approximately 75% in both), but in the service receiving the intervention this reduced to 62% whereas it remained high in the service that did not introduce the vocational specialist. Following the withdrawal of the vocational specialist the improvement was lost.ConclusionsTo enable people in first‐episode services to live meaningful and valued lives occupational functioning needs to be considered a key performance indicator. Services can improve outcome by implementing and maintaining the IPS model.
Dynamics of the continent‐wide spread of a Drosophila defensive symbiont
Authors: Cockburn Sarah N. , Haselkorn Tamara S. , Hamilton Phineas T. , Landzberg Elizabeth , Jaenike John , Perlman Steve J. 
Published: March 2013

AbstractFacultative symbionts can represent important sources of adaptation for their insect hosts and thus have the potential for rapid spread. Drosophila neotestacea harbours a heritable symbiont, Spiroplasma, that confers protection against parasitic nematodes. We previously found a cline in Spiroplasma prevalence across central Canada, ending abruptly at the Rocky Mountains. Resampling these populations 9 years later revealed that Spiroplasma had increased substantially across the region, resembling a Fisherian wave of advance. Associations between Spiroplasma infection and host mitochondrial DNA indicate that the increase was due to local increase of Spiroplasma‐infected flies. Finally, we detected Spiroplasma west of the Rocky Mountains for the first time and showed that defence against nematodes occurs in flies with a western genetic background. Because nematode infection is common throughout D. neotestacea's range, we expect Spiroplasma to spread to the Pacific coast.
Platelet transfusion in thrombocytopenic horses
Authors: Dunkel B. 
Published: March 2013

SummaryPlatelet transfusions might be indicated in horses with thrombocytopenia. The need for a transfusion cannot be determined by platelet numbers alone, as primary or co‐existing disease processes, platelet function and age of the recipient also need to be considered. In patients with no co‐morbidities, relevant bleeding is uncommonly observed with platelet counts >10 x 109/l and a therapeutic approach with initiation of treatment when signs of bleeding are observed might be justified.
Pulmonary and hepatic eosinophilic granulomas and epistaxis in a horse suggestive of multi‐systemic eosinophilic epitheliotropic disease
Authors: Horan E. M. , Metcalfe L. V. A. , de Swarte M. , Cahalan S. D. , Katz L. M. 
Published: March 2013

SummaryMulti‐systemic eosinophilic epitheliotropic disease (MEED) is a relatively uncommon disease characterised by eosinophilic infiltration of more than one organ system, with the skin and gastrointestinal tract most commonly affected. This case report describes a gelding that presented for weight loss, increased respiratory rate and effort and chronic intermittent epistaxis. Duringpost mortemexamination diffuse eosinophilic granulomatous lesions were identified in the lung and liver, leading to a diagnosis ofMEED. Veno‐occlusive pulmonary remodelling was also discovered, believed to be the cause of the chronic epistaxis and a result of the pulmonary fibrosis and eosinophilic granulomas.
Effect of simvastatin on the antihypertensive activity of losartan in hypertensive hypercholesterolemic animals and patients: Role of nitric oxide, oxidative stress, and high‐sensitivity C‐reactive protein
Authors: Abdel‐Zaher Ahmed O. , Elkoussi Alaa Eldin A. , Abudahab Lotfy H. , Elbakry Mohammed H. , Elsayed Elsayed Abu‐Elwafa 
Published: March 2013

AbstractThis study investigated whether simvastatin has antihypertensive activity and can enhance the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Hypertension and hypercholesterolemia were induced in rats by L‐NAME and cholesterol‐enriched diet, respectively. In these animals, repeated administration of simvastatin decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of losartan, and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, losartan, or simvastatin in combination with losartan to these animals increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high‐sensitivity C‐reactive protein (hs‐CRP) levels. Effects of combined treatment were greater than those of simvastatin or losartan alone. In hypertensive hypercholesterolemic patients, repeated administration of losartan decreased systolic and diastolic blood pressure, increased NO production, and decreased the elevated serum MDA and hs‐CRP levels. Addition of simvastatin to losartan therapy enhanced these effects and corrected the compromised lipid profile. Simvastatin inhibited the contractile responses of isolated aortic rings induced by angiotensin II and enhanced the inhibitory effect of losartan on this preparation. l‐arginine and acetylcholine enhanced, while L‐NAME inhibited the effects of simvastatin, losartan, and their combination on these contractile responses. Thus, simvastatin exerts antihypertensive effect in hypertensive hypercholesterolemic animals and enhances the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Besides, its cholesterol‐lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation may play an important role in these effects.
Community assembly processes shape an altitudinal gradient of forest biodiversity
Authors: Mori Akira S , Shiono Takayuki , Koide Dai , Kitagawa Ryo , Ota Aino T , Mizumachi Eri 
Published: March 2013

AbstractAimSpatial patterns in biodiversity along environmental gradients are a central theme in ecology. However, the ways in which local assembly processes control changes in species turnover (β‐diversity) along broader gradients have been less well documented. In this study, we aimed to elucidate factors and processes governing the altitudinal gradients in the β‐diversity of woody plants and ground‐dwelling oribatid mites.LocationShiretoko National Park in Hokkaido, Japan.MethodsThe diversity of plants and oribatids was investigated in seven plots (each containing 10 subplots) at different altitudes, and the β‐diversity of the two organism groups was calculated for each altitude. The dependence of β‐diversity on the size of the species pool (γ‐diversity) is an issue of long‐standing importance. We therefore used null modelling, which randomly shuffles individuals among subplots while preserving the γ‐diversity, the relative abundance of each species per plot and the number of individuals per subplot. This approach enabled us to estimate how much the observed β‐diversity deviates from the expected β‐diversity under stochastic assembly processes. Environmental data were collected to evaluate the possible effects of habitat condition/heterogeneity on community processes.ResultsIn plants, deterministic processes dominated in the low‐productivity, high‐altitude stands because of the finer‐scale niche partitioning seen among small individuals within less‐stratified stands. In the structurally developed, low‐altitude stands, the community structure was more strongly affected by stochasticity, probably resulting from one‐sided competition such that the canopy trees intercept the majority of light, a primary resource for plants, and therefore the small understorey individuals had limited access to light. Among the oribatids, the altitudinal gradient of β‐diversity was less evident than among the studied plants. However, this nonlinearity does not support the notion that local assembly processes contribute little to the spatial pattern of β‐diversity. Indeed, local‐scale environmental heterogeneity favoured a more deterministic assembly of oribatids at a given altitude.Main conclusionThe biogeographical patterns of β‐diversity are not independent of community processes and, in reality, are shaped by local stochastic/deterministic factors that change within a landscape.