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Objective To examine if transradial approach (TRA) negates the increased risk associated with femoral access in lean and morbidly obese patients undergoing percutaneous coronary intervention (PCI). Background Patients at extremes of body mass are at increased risk of bleeding after PCI. TRA has been associated with lower overall rates of bleeding compared to femoral approach. Methods and Results We studied patients undergoing emergent and elective PCI from 2010 to 2012 across 47 hospitals in Michigan who participate in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium PCI registry. The primary outcomes were the incidences of bleeding and postprocedure transfusion. Propensity matching (PM) was used to adjust for nonrandomized use of TRA. TRA was used in 10,235 procedures. In PM analyses, use of TRA was associated with a reduction in bleeding (0.80 vs. 1.9%, odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.32–0.54, P

Mortality from cerebrovascular disease increases in winter but the cause is unclear. Ireland's oceanic climate means that it infrequently experiences extremes of weather. We examined how weather patterns relate to stroke mortality in Ireland. Seasonal data for Sunshine (% of average), Rainfall (% of average) and Temperature (degrees Celsius above average) were collected for autumn (September-November) and winter (December-February) using official Irish Meteorological Office data. National cerebrovascular mortality data was obtained from Quarterly Vital Statistics. Excess winter deaths were calculated by subtracting (nadir) 3rd quarter mortality data from subsequent 1st quarter data. Data for 12 years were analysed, 2002-2014. Mean winter mortality excess was 24.7%. Winter mortality correlated with temperature (r=.60, p=0.04). Rise in winter mortality correlated strongly with the weather in the preceding autumn (Rainfall: r=-0.19 p=0.53, Temperature: r=-0.60, p=0.03, Sunshine, r=0.58, p=0.04). Winter cerebrovascular disease mortality appears higher following cool, sunny autumns.

To examine if transradial approach (TRA) negates the increased risk associated with femoral access in lean and morbidly obese patients undergoing percutaneous coronary intervention (PCI).Patients at extremes of body mass are at increased risk of bleeding after PCI. TRA has been associated with lower overall rates of bleeding compared to femoral approach.We studied patients undergoing emergent and elective PCI from 2010 to 2012 across 47 hospitals in Michigan who participate in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium PCI registry. The primary outcomes were the incidences of bleeding and postprocedure transfusion. Propensity matching (PM) was used to adjust for nonrandomized use of TRA. TRA was used in 10,235 procedures. In PM analyses, use of TRA was associated with a reduction in bleeding (0.80 vs. 1.9%, odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.32-0.54, P 0.001) and need for transfusion (1.4 vs. 2.5%, OR = 0.56, 95% CI = 0.45-0.69, P 0.001) compared with femoral access. The absolute difference in bleeding and transfusion associated with TRA was largest in patients with lean body mass (BMI 25 kg/m(2)) and morbid obesity (BMI ≥ 40 kg/m(2)): Lean patients undergoing TRA had a rate of bleeding of 1.2 versus 2.8% for femoral access (OR = 0.43, 95% CI = 0.24-0.77, P = 0.002); and rate of transfusion of 2.4 versus 3.9% (OR = 0.61, 95% CI = 0.40-0.94, P = 0.019). The morbidly obese had a rate of bleeding of 0.8% for TRA versus 2.4% for femoral access (OR = 0.33, 95% CI = 0.44-0.72, P = 0.004); and rate of transfusion of 1.7 versus 3.0%, (OR = 0.55, 95% CI = 0.30-1.0, P = 0.051).Compared with the femoral approach, TRA is associated with a reduction in bleeding across all patients undergoing PCI and the absolute benefit was greatest in those with extremely low or high BMI.

In-hospital stroke (IS) made up 6.5% of strokes recorded in the Irish National Stroke Register in 2012. International research has demonstrated poorer outcomes post IS compared to out of hospital stroke (OS). We aimed to profile all IS and OS over a 22 month period and compare the two groups by gathering data from the HIPE portal stroke register. The study site is a primary stroke centre. IS represented 11% (50/458) of total strokes with over half (27/50, 54%) admitted initially with medical complaints. IS patients had a significantly longer length of stay (79.2 +/- 87.4 days vs. 21.9 +/- 45.9 days, p0.01) and higher mortality (13/50 vs. 39/408, p0.01). Patients in the IS group were also less likely to receive stroke unit care (1/50 vs. 136/408, p0.01). This study demonstrates the significant morbidity and mortality associated with IS and highlights the need for efforts to be made to optimize identification and management of acute stroke in this cohort.

Family members of critically ill patients report dissatisfaction with family-clinician communication about withdrawing life support, yet limited data exist to guide clinicians in this communication. The hypothesis of this analysis was that increased proportion of family speech during ICU family conferences would be associated with increased family satisfaction.Cross-sectional study.We identified family conferences in intensive care units of four Seattle hospitals during which discussions about withdrawing life support were likely to occur.Participants were 214 family members from 51 different families. There were 36 different physicians leading the conferences, as some physicians led more than one conference.Fifty-one conferences were audiotaped.We measured the duration of time that families and clinicians spoke during the conference. All participants were given a survey assessing satisfaction with communication.The mean conference time was 32.0 mins with an sd of 14.8 mins and a range from 7 to 74 mins. On average, family members spoke 29% and clinicians spoke 71% of the time. Increased proportion of family speech was significantly associated with increased family satisfaction with physician communication. Increased proportion of family speech was also associated with decreased family ratings of conflict with the physician. There was no association between the duration of the conference and family satisfaction.This study suggests that allowing family members more opportunity to speak during conferences may improve family satisfaction. Future studies should assess the effect of interventions to increase listening by critical care clinicians on the quality of communication and the family experience.

Towards the development of iron oxide nanoparticles with intrinsically incorporated radionuclides for dual Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) and more recently of Single Photon Emission Computed Tomography/Magnetic Resonance Imaging (SPECT/MRI), we have developed intrinsically radiolabeled [(59)Fe]-superparamagnetic iron oxide nanoparticles ([(59)Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. (59)Fe was incorporated into Fe3O4 nanoparticle crystal lattice with 92±3% efficiency in thermal decomposition synthesis. Multidentate poly(acrylic acid)-dopamine-poly(ethylene-glycol-2000) (PAA-DOP-PEG) ligands were designed and synthesized based on facile EDC chemistry and utilized to functionalize the [(59)Fe]-SPIONs. The transverse relaxivity of [(59)Fe]-SPIONs (97±3 s(-1)mM(-1)) was characterized and found to be similar to non-radioactive SPIONs (72±10 s(-1)mM(-1)), indicating that (59)Fe incorporation does not alter the SPIONs' MRI contrast properties. [(59)Fe]-SPIONs were used to evaluate the nanoparticle biodistribution by ex vivo gamma counting and MRI. Nude mice (n=15) were injected with [(59)Fe]-SPIONs and imaged at various time points with 7T small animal MRI scanner. Ex vivo biodistribution was evaluated by tissue-based gamma counting. MRI signal contrast qualitatively correlates with the %ID/g of [(59)Fe]-SPIONs, with high contrast in liver (45±6%), medium contrast in kidneys (21±5%), and low contrast in brain (4±6%) at 24 hours. This work demonstrates the synthesis and in vivo application of intrinsically radiolabeled [(59)Fe]-SPIONs for bimodal detection and provides a proof of concept for incorporation of both gamma- and positron-emitting inorganic radionuclides into the core of metal based MRI contrast agent nanoparticles.

Fibrin thrombi form at sites of injury, where leukocytes release a variety of oxidants. To determine whether oxidants might affect proteins of the fibrinolytic system, we examined the effects of various oxidants on plasmin. Plasmin was not inhibited by micromolar concentrations of hypochlorous acid, chloramine T, or H2O2. Neither Fe nor Cu affected plasmin alone or in the presence of H2O2. However, incubation of plasmin with 5 mumol/L Cu(I or II) in the presence of the reducing agent ascorbic acid resulted in a loss of its hydrolytic activity towards proteins as well as towards small synthetic substrates. The addition of EDTA, but not mannitol, prevented its inactivation. Inactivation was prevented by the addition of catalase and accelerated by hydrogen peroxide. Preincubation of plasmin with the competitive inhibitor alpha-N-acetyl-L-lysine methyl ester prevented inactivation by Cu(II) and ascorbate. These results together suggest site-specific oxidation of plasmin's active site. Treatment of the plasminogen activators tissue plasminogen activator and two-chain urokinase-type plasminogen activator, as well as trypsin, neutrophil elastase, and thrombin with Cu(II) and ascorbate resulted in a loss of their amidolytic and proteolytic activity, indicating the general susceptibility of serine proteases to this type of oxidation. Oxidation of the zymogens Glu-plasminogen and single-chain urokinase-type plasminogen activator by Cu(II) and ascorbate resulted in the failure of these molecules to generate active enzymes when treated with plasminogen activators or plasmin, respectively. The active site His residue may be the target of oxidative inactivation, as evidenced by the partial protection afforded plasmin by the addition of Zn(II), histidine, or the platinum derivative, platinum(II) (2,2′:6′,2″- terpyridine) chloride. Because platelets contain micromolar concentrations of Cu and leukocytes are rich in ascorbate, Cu-dependent site-specific oxidation might play a role in modulating proteolytic events and the life span of thrombi formed at sites of tissue injury.

Fibrin thrombi form at sites of injury, where leukocytes release a variety of oxidants. To determine whether oxidants might affect proteins of the fibrinolytic system, we examined the effects of various oxidants on plasmin. Plasmin was not inhibited by micromolar concentrations of hypochlorous acid, chloramine T, or H2O2. Neither Fe nor Cu affected plasmin alone or in the presence of H2O2. However, incubation of plasmin with 5 mumol/L Cu(I or II) in the presence of the reducing agent ascorbic acid resulted in a loss of its hydrolytic activity towards proteins as well as towards small synthetic substrates. The addition of EDTA, but not mannitol, prevented its inactivation. Inactivation was prevented by the addition of catalase and accelerated by hydrogen peroxide. Preincubation of plasmin with the competitive inhibitor alpha-N-acetyl-L-lysine methyl ester prevented inactivation by Cu(II) and ascorbate. These results together suggest site-specific oxidation of plasmin's active site. Treatment of the plasminogen activators tissue plasminogen activator and two-chain urokinase-type plasminogen activator, as well as trypsin, neutrophil elastase, and thrombin with Cu(II) and ascorbate resulted in a loss of their amidolytic and proteolytic activity, indicating the general susceptibility of serine proteases to this type of oxidation. Oxidation of the zymogens Glu-plasminogen and single-chain urokinase-type plasminogen activator by Cu(II) and ascorbate resulted in the failure of these molecules to generate active enzymes when treated with plasminogen activators or plasmin, respectively. The active site His residue may be the target of oxidative inactivation, as evidenced by the partial protection afforded plasmin by the addition of Zn(II), histidine, or the platinum derivative, platinum(II) (2,2′:6′,2″- terpyridine) chloride. Because platelets contain micromolar concentrations of Cu and leukocytes are rich in ascorbate, Cu-dependent site-specific oxidation might play a role in modulating proteolytic events and the life span of thrombi formed at sites of tissue injury.

Objectif Rapporter la premiere experience francaise d’utilisation, en vie reelle, d’une nouvelle patch-pompe (Cellnovo) prochainement commercialisee en France. Patients et methodes Cinq patients (3♀, 2♂) diabetiques de type 1 (43,4 ± 4,5 ans, diabetiques depuis 20,6 ± 14,7 ans, mis sous pompe depuis 4,2 ± 1,3 ans) bien equilibres (HbA1c 6,8 ± 0,6 %), sans antecedents d’hypoglycemies graves et peu compliques (1 retinopathie debutante, 1 arterite distale) ont mis en place, apres une matinee de formation, le nouveau systeme mobile de gestion du diabete Cellnovo compose d’une patch-pompe unique et d’une tablette tactile envoyant, automatiquement et continuellement, par le reseau telephonique mobile, toutes les donnees du patient sur un site web securise. Ces donnees (glycemies, debits de base, boli, changement de catheter, dietetique et score d’activite physique) ont ete suivies, en temps reel, durant 2 semaines sur le site web dedie par le medecin responsable. A l’issue de cette periode, un questionnaire a ete adresse a chaque patient et une interview realisee. Resultats Les cinq questionnaires ont pu etre analyses. Sur une echelle de 1-7 (1 = pas d’accord, 7 completement d’accord), ont ete cotees les caracteristiques et facilite d’utilisation : pompe : 4,5, mesure de la glycemie : 4,2, tablette tactile : 4,1, definition des debits d’insuline : 3,6, site web securise : 4,6, base alimentaire et activite physique : 5,7, jugement global : 5. Tous les patients souhaitent garder ce systeme et le preferent au precedent. Ont ete unanimement apprecies, confort et discretion du systeme, tablette tactile, disponibilite en temps reel des donnees sur le site web et acces des donnees au medecin. Aucun incident, n’a ete rapporte durant cette periode d’observation. Conclusion Cette premiere experience met en evidence l’interet des patients et la securite du systeme pour les professionnels de sante. Declaration d’interet Les auteurs declarent avoir un interet avec un organisme prive, industriel ou commercial en relation avec le sujet presente. CellNovo.

The death of hundreds of thousands of women due to pregnancy-related complications casts a shadow over the modern obstetrical world. This paper examines the potential roles and responsibilities of professional obstetrical and midwifery associations in addressing this tolerated tragedy of maternal deaths. We examine the successes and challenges of obstetrical and midwifery associations and encourage the growth and development of active associations to address maternal mortality within their own borders. Professional associations can play a vital role in the reduction of maternal mortality worldwide. Their roles include lobbying for women's health and rights, setting standards of practice, raising awareness and team building. Associations from developed countries can influence and strengthen their colleagues within developing countries; for example, the FIGO Save the Mothers initiative. Professional associations should be encouraged to play an active role in reducing maternal mortality within their own country and abroad.

Evidence on the use of clinical practice guidelines to aid in the legal determination of negligence is increasing, specifically where they affect determinations of the standard of care and causation. So too is evidence that some clinical practice guidelines are of poor quality. An action alleging the negligent failure to diagnose and treat gestational diabetes in 1988, in which the neonate suffered permanent brachial plexus injury, entered into evidence a 1984 clinical practice guideline authored by the Society of Obstetricians and Gynaecologists of Canada. No "experts" were called to adjudicate the quality of this guideline, which cited no evidence or rationale in support of its recommendations. The standard as laid out in the guideline was judged by the court to reflect a prevailing standard of care, and a finding of negligence was rendered. As the courts pay increased attention to clinical practice guidelines, critical appraisal by the professional organizations developing these documents must occur to assure methodological rigour. Further, the quality of clinical practice guidelines should receive critical scrutiny by the courts if they are to be relied upon, even partially, to assist with legal determinations of the standard of care or issues under causation.

Objective: To review the methodologic quality of all obstetrical clinical practice guidelines developed by the Society of Obstetricians and Gynaecologists of Canada (SOGC) from 1992 to August 2001. Methods: Three reviewers independently assessed each of 37 guidelines according to a validated and reliable 37-item appraisal tool. A mean "global" score as well as three "dimension" scores were calculated for each guideline. The appraisal tool assessed each document according to three dimensions, which related to the rigour of its development (Dimension 1), its context and content (Dimension 2), and its application (Dimension 3). A repeated-measures analysis of variance was used to derive the interclass correlation coefficient. Results: Mean global quality scores ranged from 8.1 % to 54.0%. Only two guidelines were given a mean global score above 50% and 21 of the guidelines (56.8%) had mean global scores of less than 30%. Mean dimension scores were 19.9% for Dimension 1, relating to rigour of development, 47.3% for Dimension 2, relating to context and content, and 27.2% for Dimension 3, relating to application. The interclass correlation coefficient using a fixed-effects model was 0.72, reflecting reasonable agreement between the reviewers. Conclusion: Both the mean global scores and mean dimension-specific scores for the obstetrical clinical practice guidelines were lower than optimal. We were unable to reveal statistically significant improvements in guideline quality over time given the limited number of documents, but the scores for more recently drafted guidelines appear generally higher than earlier guidelines. This finding is consistent with new editorial policy adopted by the SOGC regarding guideline development. A broader review should be conducted by the SOGC on guidelines in development and under revision.

We set out to assess current understanding of MRSA among the lay public prior to writing an information booklet for relatives of patients in the ICU.

Plasma fibronectin (cold insoluble globulin) is a multiple domain glycoprotein composed of two nearly identical disulphide bridged polypeptide chains with molecular weight of 220,000. It is a substrate for factor XIIIa and binds to gelatin and heparin. After digestion of bovine fibronectin with plasmin, four fragments with Mr 29,000, 170,000, 23,000 and 6,000 have been isolated. The N-terminal 29,000 Mr fragment (259 residues) has 10 disulphide bridges within five mutually homologous domains, called “fingers”. The sequence

Since 2014, the European Bioanalysis Forum organizes a Young Scientist Symposium. The meeting format was created to provide development opportunities for young scientists to engage in international discussions. Creating a peer community of young scientists has been a proven recipe to lower the threshold and promote engagement in this community of young talents. At the same time, the meeting is aimed at stimulating collaboration between the European Bioanalysis Forum and academia.