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• Visual dipsticks for proteinuria testing have comparable accuracy to automated colorimetric readers. • Single-test accuracy is not adequate as a rule-out test for proteinuria. • Proteinuria POC testing may still be beneficial when repeated follow-up tests are performed. Objective: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. Design: Systematic review and meta -analysis. Data Sources: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. Eligibility Criteria and Data Analysis: Included studies measured the sensitivity and specificity of POC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta -analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determined heterogeneity. Main Outcome Measures: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within the subgroups test brand, reference standard, and hypertension status. Results: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta -analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. Conclusion: Visual dipsticks have comparable accuracy to automated readers, yet are not adequate as a rule-out test for proteinuria. Proteinuria POC testing may be beneficial in antenatal care when repeat follow-up tests are performed. PROSPERO Registration Number: CRD42021231914. [ABSTRACT FROM AUTHOR]

There is limited knowledge of nursing students' perspectives about engagement with special needs populations. The purpose of this study was to identify the advantages/benefits and disadvantages/challenges of nursing students' engagement experience with children with special mental and physical disabilities. Recommendations to enhance student engagement experiences were also provided. A descriptive, qualitative design was employed. Undergraduate nursing students (N = 28) responded to open-ended questions about their civic engagement experiences at a community-based, respite care program for children with special needs. Student accounts underwent directed content analysis, with coding, category and theme development according to the Theory of Planned Behavior. The Atlas.Ti computer program was used to manage the data. Advantages/Benefits : Filling cognitive and experiential learning gaps, rewarding connections/relationships, positive emotions, perceptions and interactions, and fun and stress relief. Disadvantage/challenges : Managing negative/uncomfortable emotions and uncertainty, witnessing and managing disruptive behaviors, negative perceptions of program operations/expectations. Students experienced cognitive, emotional, interpersonal and educational advantages and/or disadvantages while engaging with this defined population. To enhance engagement faculty can provide education and anticipatory guidance, detail responsibilities and expectations, and/or utilize simulation for student preparation. Nurses and researchers can utilize community based participatory methods to guide discussions with community-based organizations to collaboratively develop strategies to institute, evaluate and enhance student engagement during service learning experiences with children who have special needs. • Pedagogical strategies that involve civic engagement enhances learning • Service learning increases students' knowledge about diverse populations • Children with special needs have diverse capabilities and needs that must be known • Students must acquire knowledge about the needs of children with disabilities • Use of community based participatory research methods can facilitate collaborations and evaluation of engagement experiences [ABSTRACT FROM AUTHOR]

This work contains a description of the modified Henning operation. This technique can be proven especially useful in difficult cases of damaged meniscus (complex injuries). It consists of three stages: stable suturing of the meniscus, placement of the graft from the iliotibial band on the meniscus, and covering the graft with a collagen membrane. Stitching the meniscus provides initial stabilization, the graft from the iliotibial band provides scaffolding for the reconstructed tissue, and the collagen membrane provides biological stimulation for healing. [Display omitted] [ABSTRACT FROM AUTHOR]

• Lipid specialists may see patients with low or extremely low LDL-C. • Standard-of-care does not include genetic testing for such patients. • We used whole exome sequencing in 9 such patients. • APOB truncating mutations were the most common cause. In clinical setting, current standard-of-care does not include genetic testing for patients with low (<50 mg/dL) and extremely low (<20 mg/dL) levels of serum low-density lipoprotein-cholesterol (LDL-C). We aimed identify the underlying molecular cause – both monogenic and polygenic - of low and extremely low LDL-C levels in a cohort of patients presenting to specialty lipid clinics. Whole exome sequencing was done in patients with low or extremely low LDL-C not due to any secondary causes. Nine patients (4 women), ranging in age from 25 to 63 years old, with low or extremely low LDL-C levels were evaluated. Median LDL-C was 16 mg/dL (range undetectable - 43), total cholesterol 82 mg/dL (42 – 101), triglycerides 35 mg/dL (19–239), and high-density lipoprotein-cholesterol 45 mg/dL (24–81). Of nine patients, two carried known pathogenic variants in APOB (one stop-gain, one deletion; LDL-C range undetectable -10 mg/dL); three patients had novel APOB heterozygous mutations (two frameshift deletions and one splice site; LDL-C range undectable-13 mg/dL); two had heterozygous APOB frameshift deletions previously reported as variants of unknown significance (LDL-C 18 mg/dL in both patients); one (LDL-C 43 mg/dL) had two heterozygous mutations in PCSK9, both previously reported to be benign; and one patient (LDL-C 16 mg/dL) had the APO E2/E2 genotype along with several variants of unknown significance in genes associated with triglycerides. No patients had an LDL-C polygenic risk score below the 5th percentile (range 26th percentile to 93rd percentile). We found APOB mutations to be the most common molecular defect in patients presenting to lipid clinics with low or extremely low LDL-C. Whether clinical genetic testing and LDL-C polygenic risk scores have any utility - other than diagnostic purposes - for such patients remains unclear. In addition, further efforts may be needed to better reclassify pathogenicity of variants of unknown significance. [ABSTRACT FROM AUTHOR]

The article describes a system analysis, in the scope of conducting a personality assessment based on questionnaires and comparing it with choices made in the designed interactive story. As an effect, the authors propose an appropriate IT solution architecture, which enables two things. Gathering the data through interaction with the user and analysing the obtained results. In the visual and story part, the presented approach is using a form of comic books. The authors assume that the proposed IT solution can significantly improve the process of research about the relation between two different approaches in a personality assessment; 1) explicit text questions in questionnaires, 2) inexplicit - choices in the visual interactive story. The paper's objective is to describe the architecture of the information system in the context of psychometrics and present the current stage of the progress in designing the intelligent narration system. [ABSTRACT FROM AUTHOR]

Nutrition therapy, by enteral, parenteral, or both routes combined, is a key component of the management of critically ill, surgical, burns, and oncology patients. Established evidence indicates overfeeding (provision of excessive calories) results in increased risk of infection, morbidity, and mortality. This has led to the practice of "permissive underfeeding" of calories; however, this can often lead to inadequate provision of guideline-recommended protein intakes. Acutely ill patients requiring nutritional therapy have high protein requirements, and studies demonstrate that provision of adequate protein can result in reduced mortality and improvement in quality of life. However, a significant challenge to adequate protein delivery is the current lack of concentrated protein solutions. Patients often have fluid administration restrictions and existing protein solutions are frequently not sufficiently concentrated to deliver a patient's protein requirements. This has led to the development of new enteral and parenteral nutrition solutions incorporating higher levels of protein in smaller volumes. This review article summarizes current evidence supporting the role of higher protein intakes, especially during the early phases of nutrition therapy in acute illness, methods for assessing protein requirements, as well as, the currently available high-protein enteral and parenteral nutrition solutions. There is sufficient evidence (albeit limited from true randomized, controlled studies) to indicate that earlier provision of guideline-recommended protein intakes may be key to improving patient outcomes and that nutritional therapy that tailors caloric and protein intake to the patients' needs should be considered a desired standard of care. • Critically ill, surgical, burns, and oncology patients require nutritional therapy. • Overfeeding is detrimental to patient outcomes. • Adequate protein intakes improve morbidity, mortality, and quality of life. • Optimizing type/timing of nutrition therapy is required to improve patient outcomes. [ABSTRACT FROM AUTHOR]

In this study, we present Swift Linked Data Miner, an interruptible algorithm that can directly mine an online Linked Data source (e.g., a SPARQL endpoint) for OWL 2 EL class expressions to extend an ontology with new SubClassOf: axioms. The algorithm works by downloading only a small part of the Linked Data source at a time, building a smart index in the memory and swiftly iterating over the index to mine axioms. We propose a transformation function from mined axioms to RDF Data Shapes. We show, by means of a crowdsourcing experiment, that most of the axioms mined by Swift Linked Data Miner are correct and can be added to an ontology. We provide a ready to use Protégé plugin implementing the algorithm, to support ontology engineers in their daily modeling work. [ABSTRACT FROM AUTHOR]

Objective Obesity is associated with kidney defects. Physical activity is a key element in the treatment of obesity. The aim of this study was to compare the effect of endurance and endurance-strength training on kidney function in abdominally obese women. Methods Forty-four abdominally obese women were randomized to endurance training or endurance-strength training, three times a week for 3 months. Before and after the intervention, kidney function was assessed by measuring blood creatinine, urine creatinine, and urine albumin levels, and the albumin-to-creatinine ratio and glomerular filtration rate (GFR) were calculated. Results Renal hyperperfusion was present in both groups before the study. Following both types of physical activity, similar modifications of the investigated parameters were observed, but with no significant between-group differences. Both courses of training led to a significant increase in blood creatinine and a subsequent decrease in the GFR. A significant increase in urine creatinine and album levels, though not exceeding the range for microalbuminuria, was not accompanied by any difference in the albumin-to-creatinine ratio after endurance-strength training alone. Conclusion Three months of either endurance or endurance-strength training has a favorable and comparable effect on renal function in abdominally obese women with renal hyperfiltration. [ABSTRACT FROM AUTHOR]

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations. [ABSTRACT FROM AUTHOR]

Summary Background We analyzed the effect of peri-transplant prophylaxis on the epidemiology of bacteremia in a 12-year contemporary cohort of allogeneic HSCT recipients at our center. Methods This was an observational study of 1052 consecutive adult HSCT from 2000 to 2011. Formal prophylaxis with vancomycin only, fluoroquinolone (FQ) only, or vancomycin + FQ was implemented in 2006. The cumulative incidence of day 100 bacteremia was compared between the Early Period (2000–2005) and the Recent Period (2006–2011). Predictors for pre-engraftment bacteremia were analyzed with Cox-proportional hazard models in a subcohort of 821 HSCT who received myeloablative or reduced intensity conditioning (MA/RIC). Results The incidence of bacteremia decreased in the Recent Period (32% vs 27%; P = 0.002), whereas the rates of resistance in gram-negative rods (GNR) and vancomycin-resistant enterococci (VRE) were similar between the two Periods ( P values are not statistically significant.) In multivariate analyses, prophylaxis with vancomycin only or vancomycin + FQ was protective (HR = 0.5; CI = 0.30–0.72) and (HR = 0.3; CI = 0.12–0.52, P < 0.01). Vancomycin or vancomycin + FQ eliminated viridans streptococcal bacteremia (VSB); vancomycin + FQ decreased GNR bacteremia (HR = 0.35; CI = 0.15–0.85). Conclusions Vancomycin-based prophylaxis peri-transplant in MA/RIC HSCT was associated with elimination of VSB and may be considered at centers with high incidence of this infection. [ABSTRACT FROM AUTHOR]

This paper will systematically analyze the concept of resilience using an integrated review of literature. The historical perspective, attributes, antecedents, and consequences of resilience will be reviewed. A theoretical and operational definition will be provided. The Walker and Avant method will be used to describe the cases. Finally, the use of concept map will capture the relationships among the attributes, antecedents, consequences, and empirical indicators through clustering and chaining. [ABSTRACT FROM AUTHOR]

Abstract: Arteriovenous malformations (AVMs) are typically present at birth but may not become clinically significant till later in life. The rarity of AVMs leads to misdiagnosis, as they can be confused in young patients with infantile hemangioma (IH). Small vessel-rich AVM can be radiologically consistent with an IH, while the clinical presentation is that of a slowly growing vascular anomaly. These cases highlight the clinical dilemma that while a vascular anomaly may appear by imaging studies to be the common and generally innocuous IH, an atypical growth pattern should raise clinical suspicion for an AVM. [Copyright &y& Elsevier]

Background: Despite the increasing use of anesthesiologist-administered sedation for monitored anesthesia care (MAC) or general anesthesia in patients undergoing ERCP, limited prospective data exist on the effectiveness, safety, and cost of this approach. Objective: To prospectively assess sedation-related adverse events (SRAEs), patient- and procedure-related risk factors associated with SRAEs, and endoscopist and patient satisfaction with anesthesiologist-administered sedation. Design: Single-center, prospective cohort study. Setting: Tertiary-care referral center. Patients: A total of 528 consecutive patients undergoing ERCP. Interventions: Anesthesiologist-administered MAC or general anesthesia. Main Outcome Measurements: SRAEs, endoscopist and patient satisfaction. Results: There were 120 intraprocedure SRAEs during 109 of the 528 ERCPs (21% of cases). Intraprocedure SRAEs included hypotension (38 events), arrhythmia (20 events), O2 desaturation to less than 85% (66 events), unplanned intubation (16 events), and procedure termination (1 event). Thirty postprocedure SRAEs occurred in a total of 22 patients (4% of cases), including hypotension (5 events), endotracheal intubation (2 events), and arrhythmia (12 events). Patient-related variables associated with adverse intraprocedure events were American Society of Anesthesiologists class (P = .004) and body mass index (kg/m2) (P = .02). On a 10-point scale, mean endoscopist satisfaction with sedation was 9.2 (standard deviation 1.8) and patient satisfaction with sedation was 9.9 (standard deviation 0.7). Limitations: The approach to sedation was not randomized. Conclusions: Higher American Society of Anesthesiologists class and body mass index are associated with an increased rate of cardiac and respiratory events during ERCP. Cardiac and respiratory events are generally minor, and MAC can be considered a safe option for most ERCP patients. Despite the frequency of minor sedation-related events, procedure interruption or premature termination was rare in the setting of anesthesiologist-administered sedation. [Copyright &y& Elsevier]

The use of medication to relieve pain and inflammation after removal of third molars has been explored thoroughly in the literature. Narcotic analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, and combinations of these all have a role in the postoperative management of pain and swelling within this group of patients. This article addresses the use of NSAIDs and corticosteroids after third molar surgery, along with a review of the literature, which is incorporated to provide practitioners helpful, quick, and reliable information regarding patients undergoing third molar surgery. [Copyright &y& Elsevier]

Background and Aims: Tumor necrosis factor (TNF) superfamily members have attracted attention as new therapeutic targets for treating inflammatory disease. TNF-like weak inducer of apoptosis (TWEAK) is a unique, multifunctional TNF family cytokine that signals through its receptor, fibroblast growth factor–inducible molecule 14 (Fn14). The role of this pathway in the intestine has not been previously reported. Methods: The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model was conducted in TWEAK- or Fn14-deficient mice or in normal mice treated with a TWEAK-blocking monoclonal antibody, and clinical severity, histopathology, immunohistochemistry for cell infiltrates, TWEAK and Fn14, gene expression profiling in the colon, and systemic adaptive immunity were assessed. The effect of TWEAK on colon epithelial cell production of inflammatory mediators was analyzed in vitro. The γ-irradiation injury model was conducted in TWEAK- or Fn14-deficient mice, and crypt epithelial death was assessed. Results: Colitis severity and histologic scores were significantly reduced by TWEAK pathway deficiency or TWEAK-blocking monoclonal antibody. Neutrophil and macrophage infiltrates, chemokines, cytokines, and matrix metalloproteinase expression were reduced in the TWEAK-deficient colon after TNBS administration; however, systemic adaptive immune responses to trinitrophenyl were not altered. Fn14 is expressed on colon epithelial cells in TNBS colitis, and TWEAK induces epithelial production of pathogenic mediators. TWEAK also regulates intestinal epithelial turnover, as evidenced by reduced epithelial cell death after γ-irradiation injury in TWEAK and Fn14 knockout mice. Conclusions: Our studies elucidate a nonredundant TWEAK-intestinal epithelial cell axis and suggest that blocking TWEAK may dampen chronic intestinal inflammation and allow normal epithelial repair. [Copyright &y& Elsevier]

This paper provides a review of research on robotics in crises, disasters, and crisis management, and identifies research gaps and directions for future research. The paper analyses 74 English-language publications between 2000 and 2020 identified through the Scopus database. Seven research domains were identified: "Robot", "Human", "Public Administration", "Guards and inspections", "Private Companies", "External environment" and "Education, Training and Research". Most of the research is devoted to robots in the general context of emergencies, earthquakes, fires, and floods. Most publications are conceptual. Empirical papers mainly provide the results of experiments and case studies. A significant part of the empirical research is related to Asia-Pacific countries. This is the first study to systematically analyse scientific publications on robotics in crisis management. • Provides a review of research on robotics in crises, disasters, and crisis management. • Reviews 74 English-language publications in Scopus between 2000 and 2020. • Most of the research is devoted to robots in the general context of emergencies, earthquakes, fires, and floods. • Empirical papers mainly adopt experiments and case studies. • A significant part of the empirical research is related to Asia-Pacific countries. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide concentrations [H2O2] have been measured over the last two decades in multiple studies in surface waters in coastal, estuarine and oceanic systems. Diurnal cycles consistent with a photochemical production process have frequently being observed, with [H2O2] increasing by two orders of magnitude over the course of the day, from low nM levels in the early morning to 102 nM in late afternoon. Production rates range from <10 for off-shore ocean waters to 20–60nMh−1 for near-shore coastal and estuarine environments. Slow night-time loss rates (<10nMh−1) have been attributed to biological and particle mediated processes. Diurnal cycles have also frequently been observed in fecal indicator bacteria (FIB) levels in surf zone waters monitored for microbial water quality. Measured peak peroxide concentrations in surface coastal seawaters are too low to directly cause FIB mortality based on laboratory studies, but likely contribute to oxidative stress and diurnal cycling. Peroxide levels in the surf zone may be increased by additional peroxide production mechanisms such as deposition, sediments and stressed marine biota, further enhancing impacts on FIB in marine bathing waters. [Copyright &y& Elsevier]

Health technology assessment provides a means to assess the technical properties, safety, efficacy, cost-effectiveness, and ethical/legal/social impact of a novel technology. An important component of health technology assessment is the cost-effectiveness analysis (CEA), which can be performed using model-based CEA. This study used the CEA model to compare the cost-effectiveness of a novel ligament augmentation device with the standard technique for primary repair of complete ulnar collateral ligament (UCL) tears. A model was developed for complete UCL tear requiring acute surgical repair, comparing the cost-effectiveness of standard technique primary repair and repair using a ligament augmentation device from a societal perspective. Primary outcomes included quality-adjusted life years (QALYs), cost, net monetary benefit (NMB) and incremental NMB. A cost-effectiveness threshold of CAD $50,000/QALY was used to compare the 2 techniques. Sensitivity analyses were conducted to assess the parameter uncertainty, specifically the impact of device cost, time off work, probability of complication, and postoperative outcome. The NMB for the standard technique was CAD $42,598, and the NMB for repair using the ligament augmentation device was CAD $41,818. The standard technique was the preferred strategy for primary repair of complete UCL tears. One-way sensitivity analyses demonstrated that the ligament augmentation device became cost-effective if individuals return to work in <18 days (base case 23 days). The device was also favored when the cost was less than CAD $50 and the difference in time to return to work was at least 1 day. Our model demonstrates that there may be significant costs associated with the introduction of novel health technologies, and certain conditions, such as an earlier return to work, must be met for some devices to be a cost-effective option. This study provides an example of how model-based CEA is a useful tool to assess the cost-effectiveness of a novel device. Economic/Decision Analysis II. [ABSTRACT FROM AUTHOR]

Luminescent solar concentrators (LSCs) have attracted considerable attention in recent years for their advantages in absorbing diffusive light and increasing the cost-effectiveness of solar cells; however, the compatibility with flexible photovoltaics and the energy transfer (ET) efficiency still require improvement. In this work, amphiphilic polymer conetworks (APCNs) are employed as polymer matrices for wearable LSCs owing to their flexibility and wearability. Furthermore, with the assistance of APCNs' nanophase separated hydrophobic and hydrophilic domains, hydrophobic (Lumogen Red, acceptor) and hydrophilic (fluorescein, donor) luminescent materials are loaded in adjacent nanometer-separated domains. This results in high ET rates and broaden the acceptor's absorption range, rendering a more efficient down conversion emission. The re-emitted photons are monitored via geometry photoluminescence measurement and Monte Carlo ray tracing simulation, indicating the APCNs LSC vertically-tandem attached to the flexible photovoltaics can effectively increase the light absorbing area and be beneficial to the optimal utilization of incident light. Image 1 • Nanophase-separated amphiphilic polymers (APCNs) with a straightforward loading process enable high energy transfer between immiscible dyes. • The nano-morphology of APCNs allowed two energy transfer mechanisms, confirmed by steady-state and dynamic photoluminescence methods. • For the first time, a wearable polymer matrix for LSCs was developed that could match the requirements of wearable/ textile solar cells. [ABSTRACT FROM AUTHOR]

Allele specific real-time PCR and next-generation sequencing (NGS) are widely used to detect somatic mutation in non-small cell lung cancer (NSCLC). Both methods commonly use formalin-fixed paraffin-embedded (FFPE) tissues as diagnostic materials. Real-time PCR has the advantage of being easy to use and more tolerant of variable DNA quality, but has limited multiplex capability. NGS, in contrast, allows simultaneous analysis of many genomic loci while revealing the exact sequence changes; it is, however, more technically demanding and more expensive to employed. A challenge for both platforms is the varied limit of detection (LoD) for target genomic loci, even within the same gene. The variability of detection sensitivity may be problematic if well-known actionable somatic mutations are missed. We compared LoDs between real-time PCR and targeted NGS tests for some commonly observed EGFR mutations in NSCLC specimens. The FDA-approved real-time PCR test was superior to the NGS in detecting low level EGFR exon 19 deletion (near 1% variant allele fraction (VAF)). The cancer hotspot NGS detects low level EGFR c.2369C > T, p.T790M (2–5% VAF) better than the FDA-approved real-time PCR method. We conclude that the real-time PCR and hotspot NGS methods have complementary strengths in accurately determining clinically important EGFR mutations in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Variability in response to thienopyridines has led to the development of point-of-care devices to assess adenosine diphosphate (ADP)-induced platelet aggregation. These tests need to be evaluated in comparison to reference measurements of P2Y12 function during different thienopyridine treatments. Methods: After a run-in on 75 mg aspirin, 110 subjects were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD. Antiplatelet effects were evaluated by VerifyNow P2Y12 (VN-P2Y12) device (Accumetrics, San Diego, CA), vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, and light transmission aggregometry (LTA). Prasugrel''s and clopidogrel''s active metabolite concentration were also determined. Results: Dose- and time-dependent inhibition of P2Y12 was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y12 function. At high levels of P2Y12 inhibition, platelet function measured by VN-P2Y12 was maximally inhibited and could not reflect further changes seen with VASP or LTA methods. Correlation was also observed between exposure to clopidogrel''s active metabolite and VN-P2Y12 during MD and LD, whereas it was observed only with prasugrel MD. Conclusion: The VN-P2Y12 correlated strongly with inhibition of P2Y12 function, as measured with either VASP or LTA. VN-P2Y12 also correlated to exposure to the active metabolite of prasugrel and clopidogrel up to levels associated with assumed saturation of the P2Y12 receptor. [Copyright &y& Elsevier]

Background: The aim of this study was to compare rate of onset, magnitude, and consistency of platelet inhibition after administration of prasugrel or clopidogrel and to relate platelet inhibition to systemic exposure to each active metabolite. Thienopyridines are prodrugs, metabolized in vivo to active metabolites that inhibit the platelet P2Y12 adenosine diphosphate (ADP) receptor. Methods: This was an open-label, 2-way, crossover study that randomized healthy subjects (n = 68) to an oral loading dose (LD) of prasugrel 60 mg or clopidogrel 300 mg. Platelet aggregation response to 5 and 20 μmol/L of ADP was measured by turbidometric aggregometry. Plasma concentrations of the active metabolites of prasugrel and clopidogrel were quantified by liquid chromatography with tandem mass spectrometry detection methods. Results: Inhibition of platelet aggregation (IPA) after prasugrel was significantly higher (P < .01) than that after clopidogrel from 15 minutes through 24 hours (5 μmol/L ADP) and from 30 minutes through 24 hours (20 μmol/L ADP). For 20 μmol/L ADP, the median time to reach ≥20% IPA was 30 minutes for prasugrel and 1.5 hours for clopidogrel (P < .001). The maximum IPA was 84.1% ± 9.5% with prasugrel versus 48.9% ± 27.0% with clopidogrel for 5 μmol/L ADP and 78.8% ± 9.2% versus 35.0% ± 24.5%, respectively, for 20 μmol/L ADP (P < .001). Response to prasugrel was more consistent compared to clopidogrel (P < .01). The lower IPA response to clopidogrel was associated with lower plasma concentrations of its active metabolite (P < .001). Conclusions: Prasugrel 60 mg LD results in more rapid, potent, and consistent inhibition of platelet function than clopidogrel 300 mg LD. Lower IPA responses to clopidogrel were associated with lower concentrations of its active metabolite. [Copyright &y& Elsevier]