Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen­induced BimEL dependent apoptosis in ER+ breast cancer cells.

The epidermal growth factor receptor (EGFR) is commonly upregulated in multiple cancer types, including breast cancer. In the present study, evidence is provided in support of the premise that upregulation of the EGFR/MEK1/MAPK1/2 signaling axis during antiestrogen treatment facilitates the escape of breast cancer cells from BimEL­dependent apoptosis, conferring resistance to therapy. This conclusion is based on the findings that ectopic BimEL cDNA overexpression and confocal imaging studies confirm the pro­apoptotic role of BimEL in ERα expressing breast cancer cells and that upregulated EGFR/MEK1/MAPK1/2 signaling blocks BimEL pro­apoptotic action in an antiestrogen­resistant breast cancer cell model. In addition, the present study identified a pro­survival role for autophagy in antiestrogen resistance while EGFR inhibitor studies demonstrated that a significant percentage of antiestrogen­resistant breast cancer cells survive EGFR targeting by pro­survival autophagy. These pre­clinical studies establish the possibility that targeting both the MEK1/MAPK1/2 signaling axis and pro­survival autophagy may be required to eradicate breast cancer cell survival and prevent the development of antiestrogen resistance following hormone treatments. The present study uniquely identified EGFR upregulation as one of the mechanisms breast cancer cells utilize to evade the cytotoxic effects of antiestrogens mediated through BimEL­dependent apoptosis.

Enterprise Imaging Governance: HIMSS-SIIM Collaborative White Paper.

Enterprise imaging governance is an emerging need in health enterprises today. This white paper highlights the decision-making body, framework, and process for optimal enterprise imaging governance inclusive of five areas of focus: program governance, technology governance, information governance, clinical governance, and financial governance. It outlines relevant parallels and differences when forming or optimizing imaging governance as compared with other established broad horizontal governance groups, such as for the electronic health record. It is intended for CMIOs and health informatics leaders looking to grow and govern a program to optimally capture, store, index, distribute, view, exchange, and analyze the images of their enterprise.

Bacterial and viral infections associated with influenza.

Influenza-associated bacterial and viral infections are responsible for high levels of morbidity and death during pandemic and seasonal influenza episodes. A review was undertaken to assess and evaluate the incidence, epidemiology, aetiology, clinical importance and impact of bacterial and viral co-infection and secondary infection associated with influenza. A review was carried out of published articles covering bacterial and viral infections associated with pandemic and seasonal influenza between 1918 and 2009 (and published through December 2011) to include both pulmonary and extra-pulmonary infections. While pneumococcal infection remains the predominant cause of bacterial pneumonia, the review highlights the importance of other co- and secondary bacterial and viral infections associated with influenza, and the emergence of newly identified dual infections associated with the 2009 H1N1 pandemic strain. Severe influenza-associated pneumonia is often bacterial and will necessitate antibiotic treatment. In addition to the well-known bacterial causes, less common bacteria such as Legionella pneumophila may also be associated with influenza when new influenza strains emerge. This review should provide clinicians with an overview of the range of bacterial and viral co- or secondary infections that could present with influenza illness.

Investigation of outbreaks: epidemiology.

Outbreaks of Legionnaires' disease create high levels of public anxiety and media interest and inevitably consume a great deal of public health resources. Investigations should begin as early as possible in order to rapidly identify suspected sources of infection, control the outbreak and prevent further cases occurring. The investigations should be coordinated by an outbreak control team who work collaboratively within local/national/international public health guidelines and with clear terms of reference. The actions carried out by epidemiologists when investigating community-, hospital-, or travel-associated outbreaks are comprehensively outlined in this chapter. The microbiological and environmental actions that complement this work are discussed in the accompanying chapters.

Wet cooling systems as a source of sporadic Legionnaires' disease: a geographical analysis of data for England and Wales, 1996-2006.

BACKGROUND: The source of infection for most sporadic cases of Legionnaires' disease remains unknown. This study aims quantify the relationship between cases and wet cooling systems (WCS), a potential source of aerosolised legionella bacteria. METHODS: The study analysed data on 1163 sporadic, community-acquired cases of Legionnaires' disease in England and Wales with onset between 1996 and 2006, and 11630 postcode controls randomly sampled in proportion to population size and matched on region, age group and sex. The relationship between risk of Legionnaires' disease and distance from a WCS was analysed by conditional logistic regression. RESULTS: Cases and controls had a mean age of 56.3 years; 79.3% were male. Cases lived appreciably closer to WCS than their controls (mean distance of cases=2.11 km, controls=2.58 km; mean difference 0.47 km (95% CI 0.28 to 0.65)). The OR for disease within 1 km of a WCS compared with over 6 km (a distance taken to reflect background rates of Legionnaires' disease) was 1.59 (95% CI 1.26 to 2.01) when adjusted for socio-economic deprivation, and 1.33 (95% CI 1.04 to 1.71) when additionally adjusted for population density. The results suggest that residential proximity to a WCS may account for 19.6% of sporadic community-acquired cases. CONCLUSIONS: WCS may be an important source of sporadic, community-acquired cases of Legionnaires' disease, an observation that has important implications for health protection, especially given the likely increase in such systems as a component of strategies to improve energy efficiency in buildings.

Windscreen wiper fluid without added screenwash in motor vehicles: a newly identified risk factor for Legionnaires' disease.

A source of infection is rarely identified for sporadic cases of Legionnaires' disease. We found that professional drivers are five times more commonly represented among community acquired sporadic cases in England and Wales than expected. We therefore investigated possible risk exposures in relation to driving or spending time in a motor vehicle. A case control study including all surviving community acquired sporadic cases in England and Wales with onset between 12 July 2008 and 9 March 2009 was carried out. Cases were contacted by phone and controls were consecutively recruited by sequential digital dialling matched by area code, sex and age group. Those who consented were sent a questionnaire asking questions on driving habits, potential sources in vehicles and known risk factors. The results were analysed using logistic regression. 75 cases and 67 controls were included in the study. Multivariable analysis identified two exposures linked to vehicle use associated with an increased risk of Legionnaires' disease: Driving through industrial areas (OR 7.2, 95%CI 1.5-33.7) and driving or being a passenger in a vehicle with windscreen wiper fluid not containing added screenwash (OR 47.2, 95%CI 3.7-603.6). Not adding screenwash to windscreen wiper fluid is a previously unidentified risk factor and appears to be strongly associated with community acquired sporadic cases of Legionnaires' disease. We estimated that around 20% of community acquired sporadic cases could be attributed to this exposure. A simple recommendation to use screenwash may mitigate transmission of Legionella bacteria to drivers and passengers.

Program at home: a Veterans Affairs Healthcare Program to deliver hospital care in the home.

The Portland Veterans Affairs Medical Center (PVAMC) participated in a research-based National Demonstration and Evaluation Study of Hospital at Home Care for Elderly Patients. PVAMC continued hospital at home care in a modified form based on the results of that research phase and feedback from patients, families, and staff. The modified clinical program (referred to as Program @ Home) provided care for the same diagnoses (exacerbation of congestive heart failure, exacerbation of chronic obstructive pulmonary disease, community-acquired pneumonia, cellulitis) but differed from the research-based demonstration project in that it accepted patients of all ages, accepted early-discharge patients from the hospital, and provided a less-intensive physician and nursing model. In the first 42 months, 290 patients were admitted; 23% came from the emergency room, 54% were early hospital discharge, and the remainder came from an outpatient clinic or home care. Average length of stay was 3.2 days, and 37% were younger than 65. The results describe how a home hospital program has been integrated into the clinical care offerings of a managed care health system and how it supports inpatient, primary, emergency, and home care programs.

Aiming to improve care of older adults: an innovative faculty development workshop.

INTRODUCTION/AIMS: Internists care for older adults and teach geriatrics to trainees, but they often feel ill-prepared for these tasks. The aims of our 1-day Continuing Medical Education workshop were to improve the knowledge and self-perceived competence of general internists in their care of older adults and to increase their geriatrics teaching for learners. SETTING: Two internal medicine training programs encompassing University, Veterans Affairs, and a community-based hospital in Portland, OR, USA. PROGRAM DESCRIPTION: Course faculty identified gaps in assessment of cognition, function, and decisional capacity; managing care transitions; and treatment of behavioral symptoms. To address these gaps, our workshop provided geriatric content discussions followed by small group role plays to apply newly learned content. Forty teaching faculty participated. PROGRAM EVALUATION: Participants completed 13-item multiple-choice pre- and post-workshop geriatric knowledge tests, pre- and post-workshop surveys of self-perceived competence to care for older adults, and completed an open-ended 'commitment to change' prompt after the intervention. Knowledge scores improved following the intervention (61% to 72%, p < .0001), as did self-perceived competence (11 of 14 items significant). Seventy-one percent of participants reported success in meeting their commitment to change goals. DISCUSSION: A 1-day intervention improved teaching faculty knowledge and self-perceived competence to care for older patients and led to self-perceived changes in teaching behaviors.

Managing chronic, nonhealing wounds using a research-based protocol.

The physical, emotional, and financial costs of caring for patients with chronic, nonhealing leg wounds are substantial. In fiscal year 2001, the home care department of a large Veterans Affairs medical center in the Pacific Northwest spent nearly half of its annual budget on veterans needing wound care. In this article, the authors describe a practice improvement project designed to improve the wound care management of homebound veterans with chronic, nonhealing lower extremity wounds using a research-based protocol and consultation by a certified wound care specialist, as well as the effect of this program on home care expenditures.

Inequalities in uptake of influenza vaccine by deprivation and risk group: time trends analysis.

The aim of this study was to investigate influenza immunisation rates in the United Kingdom over a 6-year period and examine trends in uptake by deprivation, ethnicity, rurality and risk group. Influenza immunisation rates were determined from 1999/2000 to 2004/2005 using a large general practice database (QRESEARCH). There was a relative increase of 59.5% in the overall influenza vaccination rate over the study period. In 2004/2005, 70.2% of all patients aged 65 and over were vaccinated, compared with 29.3% of patients in a clinical risk group aged less than 65. Males, patients from deprived areas and from areas with a higher proportion of non-White residents had slightly lower vaccination rates overall. This general practice based study suggests that substantial increases in influenza vaccination rates have occurred across all risk groups, but that increased focus should be given to immunising high-risk patients below the age of 65.

From development to success: the European surveillance scheme for travel associated Legionnaires' disease.

BACKGROUND: EWGLINET, the European surveillance scheme for travel associated Legionnaires' disease, was established in 1987 following the identification of the disease in 1976. In 1998, the European Commission's Decision 2119/98/EC provided a legal framework for EWGLINET's operation, and its aims and objectives were formalised. Since its inception, the scheme has encountered a number of challenges which have influenced its development as a Disease Specific Network. The solutions to these challenges, and their successes, may be of interest to similar schemes. AIM: This article traces the development of the scheme and its responses to the challenges it has encountered. RESULTS: One especially significant document developed by the scheme is the European Guidelines for Control and Prevention of Travel Associated Legionnaires' Disease;(1) its history is explored. In addition, EWGLINET's relationship with collaborating centres and other groups such as tour operators is highlighted. CONCLUSIONS: Despite changing over time, the collaborations and partnerships have been maintained and continue to ensure a close cooperation, maximizing public health effects.

Uncovering frustrations. A qualitative needs assessment of academic general internists as geriatric care providers and teachers.

BACKGROUND: General internists commonly provide medical care for older adults and geriatric education to trainees, but lack the necessary knowledge and skills to fulfill these tasks. OBJECTIVE: Assess the geriatric training needs of academic general internists in 3 hospital systems in Portland, OR. DESIGN: Ten focus groups and 1 semi-structured interview. Interview transcripts were analyzed using thematic analysis, a well-recognized qualitative technique. PARTICIPANTS: A convenience sample of 22 academic general internists and 8 geriatricians from 3 different teaching hospitals. MEASUREMENTS: We elicited stories of frustration and success in caring for elderly patients and in teaching about their care. We asked geriatricians to recount their experiences as consultants to general internists and to comment on the training of Internists in geriatrics. RESULTS: In addition to deficits in their medical knowledge and skills, our Internists reported frustration with the process of delivering care to older adults. In particular, they felt ill prepared to guide care transitions for patients, use multidisciplinary teams effectively, and were frustrated with health care system issues. Additionally, general internists' approach to medical care, which largely relies on the medical model, is different from that of geriatricians, which focuses more on social and functional issues. CONCLUSIONS: Although our findings may not be broadly representative, improving our general internists' abilities to care for the elderly and to teach learners how to do the same should address deficits in medical knowledge and skills, barriers to the processes of delivering care, and philosophical approaches to care. Prioritizing and quantifying these needs and measuring the effectiveness of curricula to address them are areas for future research.

Influenza vaccine uptake in adults aged 50-64 years: policy and practice in England 2003/2004.

A small national study was carried out in England in 2003/2004 to ascertain the views of primary care trusts (PCTs) and general practitioners (GPs) on whether influenza immunisation should be extended to all people aged 50-64 years from the current recommendation of 65 years or more. Results showed that as many primary care trusts would be in favour, as would not be in favour. A similarly divided view was expressed by general practitioners. Vaccine uptake rates for high-risk (HR) and low-risk (LR) adults aged 50-64 years in the study population were higher in those practices where the GP was in favour of a more inclusive policy of offering flu vaccine to all persons aged 50 years or more, compared with those that did not favour this policy (60% versus 54% HR (p=0.02) and 16% versus 11% LR (p=0.02)). Higher rates of vaccine uptake for low-risk patients aged 50-64 years were also reported from practices where GPs perceived a greater health benefit of immunisation for this age group. Although policy for recommending vaccine to all patients aged 50 years or more is established elsewhere, opinion on whether such a policy should be adopted in England is currently divided amongst those providing local health services.

Influenza vaccine uptake and distribution in England and Wales using data from the General Practice Research Database, 1989/90-2003/04.

BACKGROUND: Routinely collected data from patients registered with general practices participating in the General Practice Research Database (GPRD) were used to analyse influenza vaccine uptake and distribution in England and Wales between 1989/90 and 1996/97. Major changes to influenza immunization policy were introduced in 1998 and 2000 when immunization of the elderly became age related rather than risk related. This new study examines trends in vaccine uptake for high- and low-risk patients and the impact of the policy changes on uptake in the elderly. METHODS: Between 0.5 and 2.7 million patients registered with practices participating in the GPRD from 1989 to 2004 were included. Data were examined by age group, medical risk group and evidence of vaccination per study year. RESULTS: Vaccine uptake among high-risk persons aged 65 or more increased from 36.7 per cent in 1989/90 to 72.1 per cent in 2003/04. For the same period, uptake rates for high-risk persons under 65 years increased from 10.8 to 24.3 per cent. For those at high risk, uptake by females was higher in all age groups up to 65 years. Of those that were vaccinated, a higher proportion of the 65 and over were vaccinated in October each year compared with the high risk under 65 (p < 0.001). CONCLUSIONS: Coverage among high-risk patients in younger age groups continues to fall well below satisfactory levels, especially among the youngest groups. Government policy should now focus on ways to improve uptake in these patients.

Healthy aging demonstration project: nurse coaching for behavior change in older adults.

The Healthy Aging Project (HAP) tested nurse coaching as a method to support healthy behavior change in older adults. The sample included 111 individuals randomized to a nurse coaching group or usual-care control group. Participants in the intervention group chose the health behaviors they wanted to change and received coaching by nurses in a single in-person session followed by telephone calls or email contact for 6 months. Nurses were trained in motivational interviewing (MI). The intervention group had significantly less illness intrusiveness and health distress than the control group at 6 months, although it is not known whether these health outcomes resulted from behavior changes. This clinical demonstration project showed that nurse-delivered MI, primarily using the telephone and email, is a feasible method to discuss behavioral change with older adults. However, future clinical trials will be needed to evaluate the efficacy of nurse-delivered MI on actual behavioral changes in older adults.

Infectious disease outbreaks in nursing homes: an unappreciated hazard for frail elderly persons.

The common occurrence and dire consequences of infectious disease outbreaks in nursing homes often go unrecognized and unappreciated. Nevertheless, these facilities provide an ideal environment for acquisition and spread of infection: susceptible residents who share sources of air, food, water, and health care in a crowded institutional setting. Moreover, visitors, staff, and residents constantly come and go, bringing in pathogens from both the hospital and the community. Outbreaks of respiratory and gastrointestinal infection predominate in this setting, but outbreaks of skin and soft-tissue infection and infections caused by antimicrobial-resistant bacteria also occur with some frequency.

Influenza vaccine uptake in the elderly: results from a rapid assessment of the effectiveness of new government policy in England for the winters 2000/2001 and 2001/2002.

Immunisation against influenza is an important means of reducing morbidity and mortality amongst high-risk groups, and especially the elderly. Although immunisation has been recommended for these groups for many years, no timely or comprehensive monitoring at the national level was carried out in England before the beginning of this century. Annual numbers of doses administered were available, but not to whom they were given. This paper describes the results of a national rapid reporting scheme for England that was introduced by the Department of Health (DH) and PHLS Communicable Disease Surveillance Centre (CDSC). The scheme collected monthly data on influenza immunisation uptake among people aged 65 or more during the winters of 2000/2001 and 2001/2002. Results showed that DH annual targets of 60 and 65%, respectively were both met, although considerable variation occurred at the local levels. The feasibility of this method of monitoring immunisation uptake in the elderly is discussed.