Implementing a resuscitation policy for patients at the end of life in an acute hospital setting: qualitative study

Objective : To explore attitudes and experiences of doctors and nurses regarding cardiopulmonary resuscitation for patients with end stage illness in an acute hospital. Design : Qualitative study; thematic analysis of two audio-taped focus groups and four semi-structured interviews. Setting : Acute district hospital, Northern Ireland. Participants : Seven nurses and nine doctors; varying nationality, gender and years of professional experience; involved in cardiopulmonary resuscitation decision-making. Results : Participants reported different interpretations of resuscitation policy and of what do not attempt to resuscitate (DNAR) decisions meant in relation to practical care for patients. This confusion in translating policy into practice contributed to communication difficulties in initiating, documenting and implementing cardiopulmonary resuscitation decisions. Participants were aware of how clinical conditions could change and reported uncertainty in determining end stage illness; they expressed fears of potential consequences of DNAR decisions for patients' care. The more disease-centred approach of doctors to patients' management, compared to nurses' more patient-centred approach, contributed to inter-professional conflict within teams. Doctors identified training needs in applying resuscitation policy and ethical principles in `real life' and nurses identified a need for ongoing professional support, which was perceived as being less available to junior doctors. Personal relationships between staff and patients, cultural reluctance to address sensitive issues and local community expectations of relatives being involved in decisions added to policy implementation difficulties. Conclusions : The findings indicate a need for ongoing staff support and training in applying resuscitation policy to decisions for patients with end stage illness in an acute hospital. They support suggestions that reviews of local resuscitation policy and of national guidelines should be undertaken with openness and honesty regarding the goals, opportunities and difficulties involved in trying to deliver good end of life care in local settings. Palliative Medicine 2007; 21 : 305—312 Key Words: do not attempt resuscitation (DNAR) • end stage illness • inter-professional • policy • resuscitation decisions

Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer

Background BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative phenotype of BRCA1-mutant tumors.

Methods We used a breast cancer disease-specific microarray to identify transcripts that were differentially expressed between paraffin-embedded samples of 17 BRCA1-mutant and 14 sporadic breast tumors. We measured the mRNA levels of estrogen receptor 1 (ESR1) ( the gene encoding ER alpha), which was differentially expressed in the tumor samples, by quantitative polymerase chain reaction. Regulation of ESR1 mRNA and ER alpha protein expression was assessed in human breast cancer HCC1937 cells that were stably reconstituted with wild-type BRCA1 expression construct and in human breast cancer T47D and MCF-7 cells transiently transfected with BRCA1-specific short-interfering RNA ( siRNA). Chromatin immunoprecipitation assays were performed to determine if BRCA1 binds the ESR1 promoter and to identify other interacting proteins. Sensitivity to the antiestrogen drug fulvestrant was examined in T47D and MCF-7 cells transfected with BRCA1-specific siRNA. All statistical tests were two-sided.

Results Mean ESR1 gene expression was 5.4-fold lower in BRCA1-mutant tumors than in sporadic tumors ( 95% confidence interval [CI]=2.6-fold to 40.1-fold, P =.0019). The transcription factor Oct-1 recruited BRCA1 to the ESR1 promoter, and both BRCA1 and Oct-1 were required for ER alpha expression. BRCA1-depleted breast cancer cells expressing exogenous ER alpha were more sensitive to fulvestrant than BRCA1-depleted cells transfected with empty vector ( T47D cells, the mean concentration of fulvestrant that inhibited the growth of 40% of the cells [IC40] for empty vector versus ER alpha: > 10(-5) versus 8.0 x 10(-9) M [ 95% CI=3.1x10(-10) to 3.2 x 10(-6) M]; MCF-7 cells, mean IC40 for empty vector versus ER alpha : > 10(-5) versus 4.9 x 10(-8) M [ 95% CI=2.0 x 10(-9) to 3.9 x 10(-6) M]).

Conclusions BRCA1 alters the response of breast cancer cells to antiestrogen therapy by directly modulating ER alpha expression.

A measure of satisfaction with food-related life

A measure of satisfaction with food-related life is developed and tested in three studies in eight European countries. Five items are retained from an original pool of seven; these items exhibit good reliability as measured by Cronbach's alpha, good temporal stability, convergent validity with two related measures, and construct validity as indicated by relationships with other indicators of quality of life, including the Satisfaction With Life and the SF-8 scales. It is concluded that this scale will be useful in studies trying to identify factors contributing to satisfaction with food-related life.

Randomised controlled trial of home-based walking programmes at and below current recommended levels of exercise in sedentary adults

Objectives: To determine, using unsupervised walking programmes, the effects of exercise at a level lower than currently recommended to improve cardiovascular risk factors and functional capacity.