Incidence of febrile neutropenia and neutropenic infections in elderly patients receiving anthracycline-based chemotherapy for breast cancer without primary prophylaxis with colony-stimulating factors

There is concern about the potential increase of hematological toxicity in elderly patients treated with chemotherapy. Recently, primary prophylaxis with colony-stimulating factors (CSFs) was proposed for elderly patients receiving moderately toxic chemotherapy. However, evidence for the benefits of this primary prophylaxis for elderly breast cancer patients is currently lacking. We retrospectively analyzed the incidence of febrile neutropenia (FN) and neutropenic infections in elderly breast cancer patients receiving anthracycline-based chemotherapy without primary prophylaxis with colony-stimulating factors. In addition, we assessed the direct costs of hospitalization for these complications. Febrile neutropenia or neutropenic infection occurred in 13% of the 46 patients. Further studies are needed to adequately evaluate the risk of neutropenic complications (NC) in elderly patients receiving standard-dose chemotherapy for breast cancer and the potential benefits of primary prophylaxis with colony-stimulating factors. © 2004 Elsevier Ireland Ltd. All rights reserved.

Extending the capabilities of the buildingEXODUS evacuation model to cater for hospital evacuations

This paper describes the extension of the building EXODUS evacuation model in order to: allow occupants to be assigned a limited set of tasks, display co-operation

The collection of pre-evacuation times from evacuation trials involving a Hospital Outpatient area and a University Library facility

This paper presents data relating to occupant pre-evacuation times from a university and a hospital outpatient facility. Although the two structures are entirely different they do employ relatively similar procedures: members of staff sweeping areas of the structure to encourage individuals to evacuate. However, the manner in which the dependent population reacts to these procedures is quite different. In the hospital case the patients only evacuated once a member of the nursing staff had instructed them to do so while in the university evacuation the students were less dependent upon the actions of the staff with over 50% of them evacuating with no prior prompting. Although this data may be useful in a variety of areas, it was collected primarily for use within evacuation models.

Survival in 176 patients with inoperable non small cell lung cancer treated initially with chemotherapy in a district general hospital

In advanced non-small cell lung cancer (NSCLC) platinum based chemotherapy with second generation drugs improves median survival (MS) to 8 months and 29% and 10% at 1 and 2 years. Platinum with a third generation drug can improve survival further (BMJ 1995;311: 899) (Spiro et al. Thorax 2004;59:828 Big Lung Trial; N Engl J Med 2003;346:92 ECOG study). NICE now recommends chemotherapy with platinum and a third generation drug for inoperable NSCLC as the first treatment modality. Methods: We audited survival of 176/461 consecutive patients referred for at least 3 courses of platinum and either gemcitabine or vinorelbine from July 2001 to December 2005. Minimal follow up 17 months. Chemotherapy was given on site. Radical radiotherapy for stage IIIA, palliative radiotherapy and second line drugs were given as felt appropriate. Results: 64% were male. 30 (17%) were <55 years ; 66 (37.5%) age 55–65 years; 63 (35.8%) aged 66–75 and 16 (9.1%) >75 years. 5 (2.8%) were stage II; 46 (26%) stage IIIA; 68 (38%) stage IIIB and 55 (30.8%) stage IV. 68 (38%) had 0– 2 courses; 63 (36%) 3 courses and 44 (25%) had 4 or more.

Demographic and temporal trends in out of hospital sudden cardiac death in belfast

Objective: To determine the epidemiology of out of hospital sudden cardiac death (OHSCD) in Belfast from 1 August 2003 to 31 July 2004.

Design: Prospective examination of out of hospital cardiac arrests by using the Utstein style and necropsy reports. World Health Organization criteria were applied to determine the number of sudden cardiac deaths.

Results: Of 300 OHSCDs, 197 (66%) in men, mean age (SD) 68 (14) years, 234 (78%) occurred at home. The emergency medical services (EMS) attended 279 (93%). Rhythm on EMS arrival was ventricular fibrillation (VF) in 75 (27%). The call to response interval (CRI) was mean (SD) 8 (3) minutes. Among patients attended by the EMS, 9.7% were resuscitated and 7.2% survived to leave hospital alive. The CRI for survivors was mean (SD) 5 (2) minutes and for non-survivors, 8 (3) minutes (p < 0.001). Ninety one (30%) OHSCDs were witnessed; of these 91 patients 48 (53%) had VF on EMS arrival. The survival rate for witnessed VF arrests was 20 of 48 (41.7%): all 20 survivors had VF as the presenting rhythm and CRI ? 7 minutes. The European age standardised incidence for OHSCD was 122/100 000 (95% confidence interval 111 to 133) for men and 41/100 000 (95% confidence interval 36 to 46) for women.

Conclusion: Despite a 37% reduction in heart attack mortality in Ireland over the past 20 years, the incidence of OHSCD in Belfast has not fallen. In this study, 78% of OHSCDs occurred at home.

A Home from Hospital service for older people.

Current policy and practice emphasises much more than ever before a need for purchasers and providers to reduce appropriately the length of hospital stay. Consequently, a number of early discharge “schemes” have been developed. This paper presents the findings from an evaluation of a “home from hospital” (HFH) scheme. The HFH service provides a maximum of six weeks intensive domiciliary care for older people on their discharge from hospital. The aim of the service is to facilitate early discharge from hospital and to assist patients to regain independence. The study reported here elicited the views and perceptions of clients and professionals involved in the HFH scheme about the quality, efficiency and effectiveness of the service. Seventy-five clients were discharged from hospital to the HFH scheme during a two month period and those who consented to participate in the study were interviewed after discharge from the HFH service (n = 40). Participants had attended hospital for various conditions but the largest group were fracture patients. Hospital staff and community based professionals completed a questionnaire about the service. Overall, clients and professionals perceived the HFH scheme as a beneficial service, though some minor problems existed at an individual level. Clients’ dependency levels generally decreased during their time on the scheme. Research using a controlled design is necessary in order to draw firm conclusions about the cost-effectiveness of a HFH service. Overall, home-from-hospital appears to be an effective model of an early discharge scheme worthy of further attention.

GP views about a home from hospital service

This paper reports the results of an investigation, by postal questionnaire, of the views of 30 General Practitioners about a model of out of hospital care – the home from hospital (HFH) service, which mainly provides social care and rehabilitation for patients in their own home. The GPs, who all worked within one of the Health and Social Services Board areas in Northern Ireland during the time of the study (March-April 1998), indicated that the introduction of the HFH service, unlike other models of out of hospital care, did not increase their workload. Therefore, it is suggested that the HFH model of care should be given more attention in terms of research evaluation and service development.

ROLE OF MULTIPLE TOLL-LIKE RECEPTOR ACTIVATION IN REGULATING CYTOTOXIC T CELL PRIMING TO LYMPOCYTIC CHORIOMENINGITIS VIRUS INFECTIONS

Foreign pathogens are recognized by toll-like receptors (TLR), present on various immune cells such as professional antigen-presenting cells (pAPCs). On recognition of its ligand, these receptors activate pAPCs, which may in turn influence naïve CD8+ T cell activation and affect their abilities to clear viral infection. However, how TLR ligands (TLR-L) can regulate CD8+ T cell responses have not been fully elucidated. This thesis will focus on examining how the presence of components from foreign pathogens, e.g. viral or bacterial infection, can contribute to shaping host immunity during concurrent viral infections. Since nitric oxide (NO), an innate effector immune molecule, was recently suggested to regulate proteasome activity; we sought to examine if NO can influence MHC-I antigen presentation during viral infections. The data in this section of the thesis provides evidence that combined TLR engagement can alter the presentation of certain CD8+ epitopes due to NO-induced inhibition in proteasome activity. Taken together, the data demonstrate that TLR ligation can influence the adaptive immune response due to induction of specific innate effector molecules such as NO. Next, the influence of combined TLR engagement on CD8+ T cell immunodominance hierarchies during viral infections was examined. In this section, we established that dual TLR2 and TLR3 stimulation alters immunodominance hierarchies of LCMV epitopes as a result of reduced uptake of cell-associated antigens and reduced cross-presentation of NP396 consequently suppressing NP396-specific CD8+ T cell responses. These findings are significant as they highlight a new role for TLR ligands in regulating anti-viral CD8+ T cell responses through impairing cross-presentation of cell-associated antigens depending on the type of TLR present in the environment during infections. Finally, we addressed TLR ligand induced type I interferon production and the signalling pathways that regulate them in two different mouse macrophage populations – those derived from the spleen or bone marrow. In this study, we observed that concomitant TLR2 stimulation blocked the induction of type I IFN induced by TLR4 in bone marrow-derived macrophages, but not spleen-derived macrophages in SOCS3-dependent manner. Taken together, the data presented in this thesis have defined new facets of how anti-viral responses are regulated by TLR activation, especially if multiple receptors are engaged simultaneously.