Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

Historical trends in survival of hospitalized heart failure patients: 2000 versus 1995

BACKGROUND: Population-based secular trends in survival of patients with congestive heart failure (CHF) are central to public health research on the burden of the syndrome. METHODS: Patients 35–79 years old with a CHF discharge code in 1995 or 2000 were identified in 22 Minneapolis-St. Paul hospitals. A sample of the records was abstracted (50% of 1995 records; 38% of 2000 records). A total of 2,257 patients in 1995 and 1,825 patients in 2000 were determined to have had a CHF-related hospitalization. Each patient was followed for one year to ascertain vital status. RESULTS: The risk profile of the 2000 patient cohort was somewhat worse than that of the 1995 cohort in both sex groups, but the distributions of age and left ventricular ejection fraction were similar. Within one year of admission in 2000, 28% of male patients and 27% of female patients have died, compared to 36% and 27% of their counterparts in 1995, respectively. In various Cox regression models the average year effect (2000 vs. 1995) was around 0.75 for men and 0.95 to 1.00 for women. The use of angiotensin converting-enzyme inhibitors and beta-blockers was associated with substantially lower hazard of death during the subsequent year. CONCLUSION: Survival of men who were hospitalized for CHF has improved during the second half of the 1990s. The trend in women was very weak, compatible with little to no change. Documented benefits of angiotensin converting-enzyme inhibitors and beta-blockers were evident in these observational data in both men and women

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Audit and feedback and clinical practice guideline adherence: Making feedback actionable

BACKGROUND: As a strategy for improving clinical practice guideline (CPG) adherence, audit and feedback (A&F) has been found to be variably effective, yet A&F research has not investigated the impact of feedback characteristics on its effectiveness. This paper explores how high performing facilities (HPF) and low performing facilities (LPF) differ in the way they use clinical audit data for feedback purposes. METHOD: Descriptive, qualitative, cross-sectional study of a purposeful sample of six Veterans Affairs Medical Centers (VAMCs) with high and low adherence to six CPGs, as measured by external chart review audits. One-hundred and two employees involved with outpatient CPG implementation across the six facilities participated in one-hour semi-structured interviews where they discussed strategies, facilitators and barriers to implementing CPGs. Interviews were analyzed using techniques from the grounded theory method. RESULTS: High performers provided timely, individualized, non-punitive feedback to providers, whereas low performers were more variable in their timeliness and non-punitiveness and relied on more standardized, facility-level reports. The concept of actionable feedback emerged as the core category from the data, around which timeliness, individualization, non-punitiveness, and customizability can be hierarchically ordered. CONCLUSION: Facilities with a successful record of guideline adherence tend to deliver more timely, individualized and non-punitive feedback to providers about their adherence than facilities with a poor record of guideline adherence. Consistent with findings from organizational research, feedback intervention characteristics may influence the feedback's effectiveness at changing desired behaviors

Surveillance of the short-term impact of fine particle air pollution on cardiovascular disease hospitalizations in New York State

<p>Abstract</p> <p>Background</p> <p>Studies have shown that the effects of particulate matter on health vary based on factors including the vulnerability of the population, health care practices, exposure factors, and the pollutant mix.</p> <p>Methods</p> <p>We used time-stratified case-crossover to estimate differences in the short-term impacts of PM_2.5on cardiovascular disease hospital admissions in New York State by geographic area, year, age, gender, co-morbid conditions, and area poverty rates.</p> <p>Results</p> <p>PM_2.5had a stronger impact on heart failure than other cardiovascular diagnoses, with 3.1% of heart failure admissions attributable to short-term PM_2.5exposure over background levels of 5 ug/m³. Older adults were significantly more susceptible to heart failure after short-term ambient PM_2.5exposure than younger adults.</p> <p>Conclusion</p> <p>The short-term impact of PM_2.5on cardiovascular disease admissions, and modifications of that impact, are small and difficult to measure with precision. Multi-state collaborations will be necessary to attain more precision to describe spatiotemporal differences in health impacts.</p

Identifying priorities in methodological research using ICD-9-CM and ICD-10 administrative data: report from an international consortium

BACKGROUND: Health administrative data are frequently used for health services and population health research. Comparative research using these data has been facilitated by the use of a standard system for coding diagnoses, the International Classification of Diseases (ICD). Research using the data must deal with data quality and validity limitations which arise because the data are not created for research purposes. This paper presents a list of high-priority methodological areas for researchers using health administrative data. METHODS: A group of researchers and users of health administrative data from Canada, the United States, Switzerland, Australia, China and the United Kingdom came together in June 2005 in Banff, Canada to discuss and identify high-priority methodological research areas. The generation of ideas for research focussed not only on matters relating to the use of administrative data in health services and population health research, but also on the challenges created in transitioning from ICD-9 to ICD-10. After the brain-storming session, voting took place to rank-order the suggested projects. Participants were asked to rate the importance of each project from 1 (low priority) to 10 (high priority). Average ranks were computed to prioritise the projects. RESULTS: Thirteen potential areas of research were identified, some of which represented preparatory work rather than research per se. The three most highly ranked priorities were the documentation of data fields in each country's hospital administrative data (average score 8.4), the translation of patient safety indicators from ICD-9 to ICD-10 (average score 8.0), and the development and validation of algorithms to verify the logic and internal consistency of coding in hospital abstract data (average score 7.0). CONCLUSION: The group discussions resulted in a list of expert views on critical international priorities for future methodological research relating to health administrative data. The consortium's members welcome contacts from investigators involved in research using health administrative data, especially in cross-jurisdictional collaborative studies or in studies that illustrate the application of ICD-10