Attitudes and beliefs of palliative care physicians regarding communication with terminally ill cancer patients.

The subject of communication between palliative care physicians and their patients regarding their diagnosis and prognosis has not been extensively researched. The purpose of this survey was to compare the attitudes and beliefs of palliative care specialists regarding communication with the terminally ill in Europe, South America, and Canada. A sample of palliative care physicians from South America (Argentina and Brazil), French-speaking Europe, and Canada were identified, and posted a questionnaire. Physicians who stated that they practised palliative care at least 30% of their time were considered evaluable as palliative care specialists. Of a total of 272 questionnaires, 228 were returned (84%); and 182/228 (81%) respondents were considered to be palliative care specialists. Palliative care physicians in all three regions believed that cancer patients should be informed of their diagnosis and the terminal nature of their illness. Physicians reported that at least 60% of their patients knew their diagnosis and the terminal stage of their illness in 52% and 24% of cases in South America, and 69% and 38% of cases in Europe, respectively. All physicians agreed that 'do not resuscitate' orders should be present, and should be discussed with the patient in all cases. While 93% of Canadian physicians stated that at least 60% of their patients wanted to know about the terminal stage of their illness, only 18% of South American, and 26% of European physicians said this (P < 0.001). Similar results were found when the physicians were asked the percentage of families who want patients to know the terminal stage of their illness. However, almost all of the physicians agreed that if they had terminal cancer they would like to know. There was a significant association between patient based decision-making and female sex (P = 0.007), older age (P = 0.04), and physicians from Canada and South America (P < 0.001). Finally, in their daily decision making, South American physicians were significantly more likely to support beneficence and justice as compared with autonomy. Canadian physicians were more likely to support autonomy as compared with beneficence. In summary, our findings suggest that there are major regional differences in the attitudes and beliefs of physicians regarding communication at the end of life. More research is badly needed on the attitudes and beliefs of patients, families, and health care professionals in different regions of the world.

Economic evaluation of the levonorgestrel-releasing intrauterine system for the treatment of dysfunctional uterine bleeding in Spain

To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency.