Fibrinogen-Coated Albumin Nanospheres Prevent Thrombocytopenia-Related Bleeding.

Thrombocytopenia (TCP) may cause severe and life-threatening bleeding. While this may be prevented by platelet transfusions, transfusions are associated with potential complications, do not always work (platelet refractory) and are not always available. There is an urgent need for a synthetic alternative. We evaluated the ability of fibrinogen-coated nanospheres (FCNs) to prevent TCP-related bleeding. FCNs are made of human albumin polymerized into a 100-nm sphere and coated with fibrinogen. We hypothesized that FCNs would bind to platelets through fibrinogen-GPIIb/IIIa interactions, contributing to hemostasis in the setting of TCP. We used two murine models to test these effects: in the first model, BALB/c mice received 7.25 Gy total-body irradiation (TBI); in the second model, lower dose TBI (7.0 Gy) was combined with an anti-platelet antibody (anti-CD41) to induce severe TCP. Deaths in both models were due to gastrointestinal or intracranial bleeding. Addition of antiplatelet antibody to 7.0 Gy TBI significantly worsened TCP and increased mortality compared to 7.0 Gy TBI alone. FCNs significantly improved survival compared to saline control in both models, suggesting it ameliorated TCP-related bleeding. Additionally, in a saphenous vein bleeding model of antibody-induced TCP, FCNs shortened bleeding times. There were no clinical or histological findings of thrombosis or laboratory findings of disseminated intravascular coagulation after FCN treatment. In support of safety, fluorescence microscopy suggests that FCNs bind to platelets only upon platelet activation with collagen, limiting activity to areas of endothelial damage. To our knowledge, this is the first biosynthetic agent to demonstrate a survival advantage in TCP-related bleeding.

The Online Sharing of Instagram Images for Rheumatoid Arthritis.

Social media use related to chronic disease has become pervasive, yet little research has been done to examine how social media is currently used by healthcare consumers or how to best use various social media platforms to improve health outcomes. The purpose of this study was to gain an understanding of Instagram use for image sharing related to #rheumatoidarthritis. A visual ethnography approach using content analysis was completed. Images for analysis (n = 106) were randomly selected, using the Instagram public search feature, during seven distinct periods. Content analysis, conducted by two coders, was used to identify categories and provide a sentiment analysis of the images. Approximately 75% of the images were determined to be positive by both coders. Social interaction and self-expression were the most frequently identified categories, suggesting that individuals use Instagram primarily for sharing awareness, sharing encouragement, and self-expression regarding rheumatoid arthritis. This finding is consistent with the use of Instagram for social networking and self-promotion. This study reveals new insights about how Instagram serves as a social, personal, and health-related information sharing platform particularly for those who may be socially isolated due to rheumatoid arthritis.

Perceived vs actual knowledge and risk of heart disease in women: findings from a Canadian survey on heart health awareness, attitudes, and lifestyle.

BACKGROUND: Heart disease is a leading cause of morbidity and mortality in men and women. Our understanding of heart disease stems chiefly from clinical trials on men, but key features of the disease differ in women. This article reports findings from the first Canadian national survey of women that focuses on knowledge, perceptions, and lifestyle related to heart health. METHODS: A cross-country survey using an adaptation of an instrument used in the United States was undertaken in spring of 2013. Based on online (208) and telephone (1446) responses from a randomly selected sample of women aged 25 or older, a total sample of 1654 weighted percentage estimates were produced. The overall response rate was 12.5%. RESULTS: Just under half of women were able to name smoking as a risk factor of heart disease, and less than one quarter named hypertension or high cholesterol. Fewer than half of women knew the major symptoms of heart disease. Most women prefer to receive information on heart health from their doctor, but only slightly more than half report that their doctor includes discussion of prevention and lifestyle during clinical consultations. CONCLUSIONS: Most women lack knowledge of heart disease symptoms and risk factors, and significant proportions are unaware of their own risk status. The findings underscore the opportunity for patient education and intervention regarding risk and prevention of heart disease.

Incorporating national priorities into the curriculum.

There are many aspects of care that need an overhaul to function safely, efficiently, and effectively. There needs to be a new culture in health care that focuses on safety and quality, and it will take many shareholders working together to make this possible. The National Priorities Partnership is a group of 28 national organizations from across the health care spectrum collaborating to change the health care delivery system. The Partners acknowledged four challenges individuals face in the current U.S. system: harm, disparity, disease burden, and waste. To meet these challenges and improve performance, the Partners identified six priorities: patient and family engagement, population health, safety, care coordination, palliative and end-of-life care, and overuse (National Priorities Partnership). It is hopeful that when put into practice, these essentials will have a significant impact on improving health care. It comes down to creating a culture of safety and quality. This culture should start during entry-level education for health care providers, such as nursing schools. The priorities and goals provide a framework that can be incorporated into the curriculum so future nurses are aware of the issues and challenges in health care today. Each challenge needs evidence-based strategies for achieving the desired results. It is time to create a culture of safety and quality in health care.

Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.

INTRODUCTION: Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions concerning the duration of anticoagulant therapy. OBJECTIVES: In this exploratory study, we investigated whether whole blood gene expression data could distinguish subjects with single venous thromboembolism from subjects with recurrent venous thromboembolism. METHODS: 40 adults with venous thromboembolism (23 with single event and 17 with recurrent events) on warfarin were recruited. Individuals with antiphospholipid syndrome or cancer were excluded. Plasma and serum samples were collected for biomarker testing, and PAXgene tubes were used to collect whole blood RNA samples. RESULTS: D-dimer levels were significantly higher in patients with recurrent venous thromboembolism, but P-selectin and thrombin-antithrombin complex levels were similar in the two groups. Comparison of gene expression data from the two groups provided us with a 50 gene probe model that distinguished these two groups with good receiver operating curve characteristics (AUC 0.75). This model includes genes involved in mRNA splicing and platelet aggregation. Pathway analysis between subjects with single and recurrent venous thromboembolism revealed that the Akt pathway was up-regulated in the recurrent venous thromboembolism group compared to the single venous thromboembolism group. CONCLUSIONS: In this exploratory study, gene expression profiles of whole blood appear to be a useful strategy to distinguish subjects with single venous thromboembolism from those with recurrent venous thromboembolism. Prospective studies with additional patients are needed to validate these results.

A patient and carer survey in a community clinical nurse specialist service.

The community clinical nurse specialist (CNS) team provides specialist palliative care to clients with cancer and non-malignant, life-limiting diseases in clients' homes, community hospitals, and residential and nursing homes. CNSs are based in health centres, community hospitals (geographically spread around the county) or at the local hospice. There has been no systematic review of patient and carer levels of satisfaction since the conception of the CNS service in 1984. Accredited as a nursing development unit (Flint and Wright, 2001) by Leeds University, the team has been encouraged to obtain service users' views. National guidelines in the UK (National Institute for Health and Clinical Excellence (NICE), 2004) also recommend that systems be put in place to enable clients to make their voices heard in a variety of ways. The principle aim was to identify the level of patient and carer satisfaction and to highlight aspects of care that warranted alteration or improvement. The CNS team were also keen to identify the aspects of their role most helpful to patients and carers, enabling CNSs to spend their time in a way that is most beneficial to clients.

Phase II study of neoadjuvant docetaxel, vinorelbine, and trastuzumab followed by surgery and adjuvant doxorubicin plus cyclophosphamide in women with human epidermal growth factor receptor 2-overexpressing locally advanced breast cancer.

PURPOSE: To evaluate the combination of docetaxel, vinorelbine, and trastuzumab as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)--overexpressing breast cancer. PATIENTS AND METHODS: Patients with stage IIB or III breast cancer, including inflammatory disease, and HER2 overexpression (determined by fluorescent in situ hybridization) were treated with six cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 administered every 14 days with granulocyte colony-stimulating factor and quinolone prophylaxis. Trastuzumab was administered as a 4 mg/kg loading dose followed by 2 mg/kg weekly for 12 weeks. The primary efficacy end point was pathologic complete response (pCR) in the breast. RESULTS: Of 31 enrolled patients, 68% had T3 or T4 tumors and 90% were clinically node positive. Twelve patients (39%; 95% CI, 21.6% to 55.9%) achieved pCR in the breast and lymph nodes and 14 patients (45%; 95% CI, 27.6% to 62.7%) achieved pCR in the breast alone, and 19 patients (61%; 95% CI, 44.1% to 78.4%) were node negative after neoadjuvant therapy. Clinical response was documented in 29 patients (94%; 95% CI, 78.6% to 99.2%) with 26 complete responses (84%; 95% CI, 70.9% to 96.8%). The most commonly reported grade 3/4 toxicities were neutropenia (97%), febrile neutropenia (22%), anemia (6%), mucositis/stomatitis (6%), constipation (6%), and skin rash (6%). CONCLUSION: With clinical response and pCR rates of 94% and 39%, respectively, docetaxel, vinorelbine, and trastuzumab is a highly active neoadjuvant therapy for HER2-overexpressing locally advanced breast cancer. Although well tolerated overall, significant febrile neutropenia was observed despite prophylactic measures; therefore, evaluating a similar regimen using lower docetaxel and/or vinorelbine doses is warranted.

Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.

BACKGROUND: The purpose of this study was to evaluate the combination of docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally advanced breast cancer. PATIENTS AND METHODS: Eligible women with stage IIA-IIIB or locoregional stage IV breast cancer were treated before surgery with 6 cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every 2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic complete response (pCR), viewed as an early surrogate for disease-free and overall survival, was the primary efficacy endpoint. Sixty patients were enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and 52% were hormone receptor positive. RESULTS: Fifty-nine patients were evaluable for pathologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX), 20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5 mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical response rate was 98% (59 of 60 patients), including 38 complete responses (63%). Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%) occurred in >or= 5% of patients. Constipation was seen early but became insignificant after incorporating a prophylactic laxative regimen. Other toxicities have been minimal. CONCLUSION: With a clinical response rate of 98% and an in-breast pCR rate of 27%, docetaxel/vinorelbine is among the most active neoadjuvant regimens reported for locally advanced breast cancer. Docetaxel/vinorelbine can be administered in a dose-dense fashion while maintaining relative dose intensity. However, there was a significant incidence of fever and neutropenia despite the use of prophylactic growth factors and quinolones, indicating that lower doses of docetaxel/vinorelbine should be evaluated in future studies.

Caring Connection: Internet resources for family caregivers of children with cancer.

This poster will describe the evaluation of a family-focused web-based resource, the "Caring Connection", designed to provide individualized clinical information, patient-centric information resources, and access to online family-to-provider and family-to-family communication for caregivers of children with cancer. Data from structured interviews with family caregivers describe their Internet use and information needs. The interview data further provide information regarding the information and communication needs of family caregivers of children with cancer. Website server logs provide data to corroborate the interview findings.

Caring connection: developing an Internet resource for family caregivers of children with cancer.

This article describes the development of a family-focused Internet resource, the Caring Connection Web site, designed to provide individualized clinical information, patient-centered information, and access to online communication for caregivers of children with cancer. Data from surveys with family caregivers described the scope and characteristics of their current Internet use. Web site prototype development and user testing provided additional insights that inform the ongoing design of the Caring Connection Web site. The family caregivers and oncology healthcare providers who participated are active users of Internet health information. The preliminary data they provided support the feasibility and usability of the Caring Connection prototype. Ongoing development of the Caring Connection Web site will provide an innovative approach to assist these family caregivers in meeting currently unmet information and communication needs, and will provide evidence regarding "best practice" in design and development of Internet resources to support communication and information sharing.

Identification of DNA markers for a transmissible Pseudomonas aeruginosa cystic fibrosis strain.

A number of transmissible Pseudomonas aeruginosa strains have been identified which potentially constitute an emerging threat to patients with cystic fibrosis (CF). We sought to identify DNA markers that were specific to a transmissible P. aeruginosa CF clone and evaluate these probes on a large collection of genotypically distinct P. aeruginosa strains. Using subtractive DNA hybridization, in combination with analysis using the P. aeruginosa PAO1 genome chip, DNA markers specific for or absent from the Manchester transmissible CF strain (MA) were identified. Five subtractive DNA hybridization markers (MA15, MA18, MA21, MA22, and MA30) were found to be specific to strain MA and were located within a novel 13,318-bp genomic island, designated the MA island. The MA island encoded 18 genes and consisted of two bacteriophage-like regions; one region encoded the MA-specific subtractive hybridization markers, while the other bacteriophage-like region contained a Vibrio cholera-like toxin gene. Probes MA15, MA18, MA21, MA22, and MA30 were all found to be specific to strain MA when a collection of 141 P. aeruginosa strains was examined by hybridization with each DNA marker. In contrast, a previously isolated DNA marker for the Liverpool transmissible CF strain, PS21, was not found to be specific, detecting two additional strain types in the collection screened. Both the Manchester and Liverpool strain types were not encountered in CF populations outside the United Kingdom. The MA genomic island and Vibrio cholera-like toxin gene within it constitute novel genetic factors associated with a transmissible P. aeruginosa strain and their role in pathogenesis remains to be determined.

Caring Connection: developing an Internet resource for family caregivers of children with cancer.

This poster will describe the development of a family-focused, web-based resource, the "Caring Connection", designed to provide individualized clinical information, patient-centered information resources, and access to online family-provider and family-to-family communication for caregivers of children with cancer. Data from structured interviews with family caregivers and healthcare providers describe their current Internet use and information needs. Website prototype development and user testing provide additional insights that are informing the ongoing design of the "Caring Connection" website.

Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene.

BACKGROUND: Denys-Drash syndrome (DDS) is associated with mutations of the Wilms' tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive glomerulopathy, and the development of Wilms' tumour. More than 90% of patients with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%) for the development of Wilms' tumour. WT1 is a signalling protein with 90% of WT1 mutations occurring in the WT1 zinc finger region as single nucleotide polymorphisms, the majority of which are missense mutations. METHODS: Constitutional DNA was extracted from peripheral blood. Direct sequencing and restriction enzymes were employed to analyse mutations. RESULTS: Two children, 46XY males who had evidence of pseudohermaphroditism, hypogonadism and renal failure with a glomerulopathy atypical for DDS, but no Wilms' tumour or nephroblastomatosis, on investigation, prior to transplant, were identified with missense mutations in the WT1 gene, in exons 8 and 9, respectively. The decision to do prophylactic nephrectomies was based on the genetic identification of WT1 mutations supporting a diagnosis of incomplete DDS, with the potential for increased risk of malignancy with the development of Wilms' tumour. The nephrectomy specimens demonstrated nephrogenic rests (nephroblastomatosis), which have a potential for malignant transformation. CONCLUSIONS: WT1 missense mutations in exons 8 and 9 can be regarded as having the potential for malignant change supporting prophylactic nephrectomy in apparent incomplete DDS patients with end-stage renal disease.

Computers in patient education.

Nurses in practice have an increasing need to become aware of the computer-based resources available and the evidence regarding their use in the process of patient education. This synthesis of the literature examines research related to computer-based patient education. A particular focus is placed on the nurse clinician's perspective and the role of the nurse as a patient educator in the digital age. Two primary healthcare database resources, MEDLINE and CINAHL, were selected for review of the current literature. A listing of articles related to the use of computer technology in patient education was obtained from both of these databases. The search strategy included exploding the subject heading terms "computer" and "patient education," and included articles from 1971 to 2001. Computer-based patient education is an effective strategy for improving healthcare knowledge and clinical outcomes. Computer-based learning can be tailored to the individual's age and specific learning needs. Furthermore, although access to computer-based resources continues to be a barrier for some, socioeconomic disparities have no reported impact on patients' abilities to use computer-based technologies effectively.