The challenge of patients’ unmet palliative care needs in the final stages of chronic illness.

Background: There is consensus in the literature that the end of life care for patients with chronic illness is suboptimal, but research on the specific needs of this population is limited. Aim: This study aimed to use a mixed methodology and case study approach to explore the palliative care needs of patients with a non-cancer diagnosis from the perspectives of the patient, their significant other and the clinical team responsible for their care. Patients (n 18) had a diagnosis of either end-stage heart failure, renal failure or respiratory disease. Methods: The Short Form 36 and Hospital and Anxiety and Depression Questionnaire were completed by all patients. Unstructured interviews were (n 35) were conducted separately with each patient and then their significant other. These were followed by a focus group discussion (n 18) with the multiprofessional clinical team. Quantitative data were analysed using simple descriptive statistics and simple descriptive statistics. All qualitative data were taped, transcribed and analysed using Colaizzi’s approach to qualitative analysis. Findings: Deteriorating health status was the central theme derived from this analysis. It led to decreased independence, social isolation and family burden. These problems were mitigated by the limited resources at the individual’s disposal and the availability of support from hospital and community services. Generally resources and support were perceived as lacking. All participants in this study expressed concerns regarding the patients’ future and some patients described feelings of depression or acceptance of the inevitability of imminent death. Conclusion: Patients dying from chronic illness in this study had many concerns and unmet clinical needs. Care teams were frustrated by the lack of resources available to them and admitted they were ill-equipped to provide for the individual’s holistic needs. Some clinicians described difficulty in talking openly with the patient and family regarding the palliative nature of their treatment. An earlier and more effective implementation of the palliative care approach is necessary if the needs of patients in the final stages of chronic illness are to be adequately addressed. Pa

Two functionally linked amino acids in the stem 2 region of measles virus haemagglutinin determine infectivity and virulence in the rodent central nervous system.

Rodent brain-adapted measles virus (MV) strains, such as CAM/RB and recombinant MVs based on the Edmonston strain containing the haemagglutinin (H) of CAM/RB, cause acute encephalitis after intracerebral infection of newborn rodents. We have demonstrated that rodent neurovirulence is modulated by two mutations at amino acid positions 195 and 200 in the H protein, one of these positions (200) being a potential glycosylation site. In order to analyse the effects of specific amino acids at these positions, we introduced a range of individual and combined mutations into the open reading frame of the H gene to generate a number of eukaryotic expression plasmids. The functionality of the mutant H proteins was assessed in transfected cells and by generating recombinant viruses. Interestingly, viruses caused acute encephalitis only if the amino acid Ser at position 200 was coupled with Gly at position 195, whereas viruses with single or combined mutations at these positions, including glycosylation at position 200, were attenuated. Neurovirulence was associated with virus spread and induction of neuronal apoptosis, whereas attenuated viruses failed to infect brain cells. Similar results were obtained by using primary brain-cell cultures. Our findings indicate that a structural alteration in the stem 2 region of the H protein at position 195 or 200 interferes with infectivity of rodent neurons, and suggest that the interaction of the viral attachment protein with cellular receptors on neurons is affected.

A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

The coronavirus main protease, Mpro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential Mpro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed Mpro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a Ki value of 35.3 M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.