Lyophilised reconstituted human platelets increase thrombus formation in a clinical ex vivo model of deep arterial injury

Platelets are the principal component of the innate haemostatic system that protect from traumatic bleeding. We investigated whether lyophilised human platelets (LHPs) could enhance clot formation within platelet-free and whole blood environments using an ex vivo model of deep arterial injury. Lyophilised human platelets were produced from stored human platelets and characterised using conventional, fluorescent and electron microscopic techniques. LHPs were resuspended in platelet-free plasma (PFP) obtained from citrated whole human blood to form final concentrations of 0, 20 and 200 x 10? LHPs/L. LHPs with recalcified PFP or whole blood were perfused through the chamber at low (212 s?1) and high (1,690 s?1) shear rates with porcine aortic tunica media as thrombogenic substrate. LHPs shared morphological characteristics with native human platelets and were incorporated into clot generated from PFP or whole blood. Histomorphometrically measured mean thrombus area increased in a dose-dependent manner following the addition of LHPs to PFP under conditions of high shear [704 μm2 ± 186 μm2 (mean ± SEM), 1,511 μm2 ± 320 μm2 and 2,378 μm2 ± 315 μm2, for LHPs at 0, 20 and 200 x 10? /l, respectively (p= 0.012)]. Lyophilised human platelets retain haemostatic properties when reconstituted in both PFP and whole blood, and enhance thrombus formation in a model of deep arterial injury. These data suggest that LHPs have the potential to serve as a therapeutic intervention during haemorrhage under circumstances of trauma, and platelet depletion or dysfunction.     

Major motives in non-acceptance of A/H1N1 flu vaccination: the weight of rational assessment

Recent efforts of health authorities to promote vaccination against influenza A/H1N1 were met with low compliance rates in most industrialized countries. Here we analyzed the attitudes of the Israeli public towards A/H1N1 vaccination based on a telephone survey conducted several months after the peak of the outbreak. The findings attest to the low uptake of the A/H1N1 vaccine (17%) in Israel, and identify the socio-demographic characteristics associated with non-compliance. In addition, the survey reveals passiveness, fear and distrust as motives leading to non-compliance. Most importantly, the study identified the substantial weight of reflective assessment in the attitude of lay individuals towards the A/H1N1 vaccine. As many as 30% of the non-vaccinated responders provided reasoned arguments for rejecting the vaccine, based mainly on assessment of threat versus actual risk. These observations highlight the need to consider the opinion of the lay public when implementing new vaccination programs.     

Identifying Tyrosine Kinase Inhibitor Nonadherence in Chronic Myeloid Leukemia: Subanalysis of TAKE-IT Pilot Study

Background

There are inconsistencies in reports on correlates for nonadherence (NA) to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). The diagnostic accuracy of subjective adherence measures using electronic monitoring (EM) as the reference standard is yet to be determined. This study aimed to evaluate correlates of TKI NA using EM and test the diagnostic accuracy of subjective adherence measures.

Victims of dating violence among high school students. Are the predictors different for males and females?

This study explores the gender differences in the experience of dating violence by using a multivariate approach and sampling a racially/ethnically and socioeconomically diverse population. The social learning theory and feminist theory were the theoretical frameworks used to guide this study. The final sample included 939 students (385 boys and 554 girls) in public high schools in the Los Angeles area. The data revealed that gender differences are not significant to the total dating violence experienced. Males reported physical abuse (e.g., being slapped and hit with a fist or object) more often than females, while females reported significantly more sexual abuse than males. Both males and females reported that males were more frequently the initiators of dating violence. With regard to perceived causes of dating violence, victims in both sexes indicated that the most frequent reason for their partners? violence was jealousy. For many males, females? use of physical aggression in dating relationships is not taken seriously, possibly because difference in physical strength. The females? responses to violence indicated greater emotional and psychological injury. Finally, this study identified 4 predictor variables that differ significantly by gender; namely, race, self-esteem, justification of violence, and infliction of dating violence.     

Cognitive endpoints as disease biomarkers: optimizing the congruency of preclinical models to the clinic

Cognition is a complex set of processes, including attention, learning and memory, that refers to the capacity to encode, consolidate, store and retrieve recent and remotely stored fact (semantic) and experience-based (episodic) memory. The development of cognitive enhancers is of particular importance to society and the pharmaceutical industry, as cognitive dysfunctions are observed across a wide range of neuropsychiatric and neurodegenerative disorders; however, developing such therapeutics has proven difficult. There is poor congruency between the abundance of positive results observed in animal studies compared with clinical outcome. For example, from 1982 to 2002 there was a 6000% increase in studies on cognitive processing in rodents that had little or no impact on the outcome of phase II and III clinical trials. The effects of therapeutics on models of cognition that demonstrate the potential to improve preclinical-to-clinical congruency, focusing on attention, impulsivity and episodic memory, are summarized in this review. Changes in attention, impulsivity and episodic memory are tractable 'disease biomarkers' that correlate with the disease phenotypes that are potential therapeutic targets. In the context of the development of cognitive enhancing drugs, one of the major goals of translational medicine is to improve the congruency between preclinical models and clinical results. Improved translatability could improve discovery, validation and implementation of biomarkers to inform clinical outcome studies and decision making, and to establish proof-of-concept for efficacy and safety based on targeted mechanisms of action.     

Acute chest pain — identification of patients at low risk for coronary events. The impact of symptoms, medical history and risk factors

BACKGROUND: The evaluation of patients with acute chest pain remains challenging, as it implies the risk of fatal misdiagnosis. It is well recognized that typical angina does not specifically identify patients at high risk. We investigated the predictive value of characteristics atypical for myocardial ischemia for exclusion of acute or subacute coronary events, focusing on patients' symptoms, medical history and risk factors. METHODS: We prospectively studied 1288 consecutive patients presenting with acute chest pain at a non-trauma emergency department. Patients' symptoms, history and risk factors were evaluated using seven predefined criteria and assigned as typical or atypical for ischemic coronary chest pain. Positive predictive value (PPV) and 95% confidence intervals (95% CI) were calculated to predict or exclude acute myocardial infarction (AMI) and major adverse cardiac events (MACE: cardiovascular death, percutaneous coronary interventions, bypass surgery, or myocardial infarction) within six months. RESULTS: AMI occurred in 168 patients (13%), and 6-months MACE (including AMI) overall in 240 patients (19%). Presence of four or more criteria typical for myocardial ischemia was associated with a PPV of 0.21 (0.17 to 0.25) for predicting AMI and 0.30 (0.25 to 0.35) for 6-months MACE. Presence of four or more criteria atypical for coronary ischemia was associated with a PPV of 0.94 (0.91 to 0.96) for excluding AMI and 0.93 (0.90 to 0.96) for excluding 6-months MACE. In 165 of 476 patients under 40 years of age (35%), four or more atypical criteria excluded AMI and 6-months MACE with PPVs of 0.98 (0.96 to 1.0). CONCLUSION: Evaluation of criteria atypical for myocardial ischemia with acute chest pain may help to identify candidates for early discharge, whereas typical characteristics have very little diagnostic value.     

Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws

Objectives:  To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated.
Design:  Retrospective case review.
Methods:  The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants ( n  = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis.
Main outcome measures:  The McNemar, Kruskall–Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity.
Results:  Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla ( P  < 0.001) but not in the mandible ( P  = 0.178). The total number of radiographic signs per patient increased with BONJ stage.
Conclusion:  Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis.