La spectaculaire Jaclyn Case

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La spectaculaire Jaclyn Case
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La relation médecin-malade a évolué au cours des dernières décennies vers un rôle croissant du patient dans les décisions médicales. Dans le domaine de la fin de vie, deux lois en dix ans sont venues renforcer l’autonomie des malades. L’accroissement des capacités et des pouvoirs de la médecine a conduit à créer des situations inédites. Dans certaines de ces situations, l’ensemble des possibilités médicales sont déployées pour une prolongation artificielle de la vie, sans que le bénéfice pour le patient ne soit clair alors que les nuisances peuvent être insoutenables. On parle alors d’obstination déraisonnable ou d’acharnement thérapeutique.Cette évolution globale de la médecine se retrouve pour les traitements médicaux des cancers. L’évolution récente des thérapeutiques médicales a été considérable faisant naitre puis croitre une forte demande de prolongation de vie et de guérison chez les patients. Pourtant, la plupart des cancers en situation métastatique demeurent incurables et sont fréquemment mortels. Le parcours du malade incurable en cancérologie, du diagnostic à la fin de vie, va comporter de nombreuses décisions pour lesquelles différents arguments peuvent être mis en balance. La prise de décision dans ce contexte est souvent complexe et difficile. Des études internationales montrent un niveau élevé de soins agressifs en fin de vie et ce phénomène s’amplifie au cours des dernières années.Le contraste est saisissant entre, d’un côté la demande de la société civile se traduisant par les évolutions législatives récentes renforçant les droits des malades en fin de vie, et de l’autre côté le haut niveau d’agressivité dans le soin en fin de vie ainsi que son augmentation. Ce contraste témoigne d’une tension persistante dans le processus décisionnel, y compris en fin de vie. Cette tension est particulièrement forte en cancérologie où les décisions médicales en fin de vie sont nombreuses.Cette thèse, dans le cadre d’une démarche éthique, explicite le cadre du soin et les spécificités de la cancérologie puis cherche à définir et à caractériser l’obstination déraisonnable en cancérologie. Les études réalisées proposent des moyens de lutter contre l’obstination déraisonnable. D’abord en renforçant la place du patient dans les décisions en fin de vie, dans le cadre de discussions anticipées. Puis en limitant le risque d’erreur dans le processus décisionnel du cancérologue grâce à une médecine intégrée. Enfin, une action sur le discours du cancérologue, semble être une voie de recherche prometteuse.
Résumé

Objectif
Dans le cadre, d’un projet de compagnonnage à destination des soignants du domicile, notre Equipe Mobile de Soins Palliatifs a souhaité évaluer leur niveau de qualification en soins palliatifs.

Matériel et méthode
Un QCM de 20 questions a été créé afin d’explorer le niveau de formation, d’expérience et de connaissances en soins palliatifs. Il a été soumis à toutes les infirmières libérales installées sur la communauté de commune du Grand Pontarlier, soit 20 infirmières. Ce travail original a fait l’objet d’un mémoire de DIU soins palliatifs.

Résultats
Le taux de réponse est de 85 %. Le niveau de formation et d’expérience est très faible. Aucune infirmière n’a de diplôme universitaire ou d’expérience en équipe mobile ou unité de soins palliatifs. La prise en charge des symptômes et les lois de soins palliatifs sont peu connues.

Conclusion
La méthode est simple. Elle peut être utilisée par d’autres équipes pour évaluer d’autres professionnels de santé. Ce travail a suscité un vif intérêt de la part des infirmières libérales, sans doute parce que si elles suivent peu de patients en soins palliatifs chaque année, leurs difficultés sont réelles. Ces difficultés, révélées dans d’autres travaux, peuvent être mises en lien avec le faible niveau de formation et d’expérience mis en évidence. Notre travail de formation devra permettre une meilleure qualité de prise en charge du patient.
Background Although advance care planning (ACP) is recognised as intégral to quality cancer care, it remains poorly integrated in many settings. Given cancer patients' unpredictable disease trajectories and equivocal treatment options, a disease specific ACP model may be necessary.
Aims To examine how Australian cancer patients consider ACP and inform the development of an Australian Cancer Centre's ACP programme.
Methods A constructivist research approach drawing on the Medical Research Council framework for complex interventions. Participants described their initial understanding of ACP, received ACP information, and finally completed a semi-structured interview assisted by the vignette technique. Qualitative inter-rater reliability was integrated.
Results Twenty-nine patients from the lung and gastro-intestinal tumour streams were approached with 18 completing the study. Participants initially had scant knowledge of ACP. On obtaining further information, their responses indicated that: For cancer patients, ACP is an individualised, dynamic, and shared process characterised by myriad variations in choices to actualise, relinquish, and/or reject its individual components. Actualisation of each component involves considering, possibly conversing about, planning, and communicating a decision, usually iteratively. Reactions can change over time and are informed by values, memories, personalities, health perceptions, appreciation of prognoses, and trust or doubts in their substitute decision makers.
Discussion/Conclusion Findings endorse the value of routinely, though sensitively discussing ACP with cancer patients at various times points across their disease trajectory. Nonetheless, ACP may also be relinquished or rejected and ongoing offers for ACP in some patients may be offensive to their value system.
Background:
Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

Methods:
Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

Findings:
2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

Interpretation:
Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

Funding:
Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.
Purpose:
To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer.

Patients and methods:
This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences.

Results:
Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses.

Conclusion:
Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship.
Background:
Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.

Methods:
We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.

Results:
A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.

Conclusions:
Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).
BACKGROUND: On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer. METHODS: We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival. RESULTS: A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects. CONCLUSIONS: Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer.
To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients' subsequent intensive medical care and place of death.
Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer.
Eight outpatient oncology clinics in the United States.
386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died.
Primary outcomes: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients' place of death (for example, intensive care unit). Secondary outcomes: survival, late hospice referrals (≤1 week before death), and dying in preferred place of death.
216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% v 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% v 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% v 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% v 66%; -10.8%, -1.0% to -20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% v 80%; adjusted risk difference -9.4%, -0.8% to -18.1%).
The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients' attainment of their goals.
PURPOSEThis study tested the efficacy of an intervention on end-of-life decision making for patients with advanced cancer. PATIENTS AND METHODS
One hundred twenty patients with metastatic cancer who were no longer being treated with curative intent (and 87 caregivers) were randomly assigned to the intervention (n = 55) or treatment as usual (n = 65). Primary outcome measures were the proportion of patients with do-not-resuscitate (DNR) orders, timing of DNR orders, and place of death. Secondary outcome measures were completed at study enrollment, 3 weeks later, and 3 months later, including patients' knowledge, mood, and caregiver burden.ResultsHigh, but equivalent, rates of DNR orders were observed in both groups. In per-protocol analyses, DNR orders were placed earlier for patients who received the intervention (median, 27 v 12.5 days; 95% CI, 1.1 to 5.9; P = .03) and they were more likely to avoid a hospital death (19% v 50% (95% CI, 11% to 50%; P = .004). Differences between the groups over time were evident for estimates of cardiopulmonary rehabilitation (CPR) success rates (P = .01) but not knowledge of CPR (P = .2). There was no evidence that the intervention resulted in more anxious or depressive symptoms. Caregivers experienced less burden in terms of disruption to schedule if the patient received the intervention (P = .05). CONCLUSION
An intervention, consisting of an informational pamphlet and discussion, was associated with earlier placement of DNR orders relative to death and less likelihood of death in hospital. There was no negative impact of the intervention on secondary outcomes, although the sample may have been too small to detect differences.
PURPOSEEmerging evidence suggests muscle depletion predicts survival of patients with cancer. PATIENTS AND METHODS
At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models.ResultsBody mass index (BMI) distribution was 17% obese, 35% overweight, 36%
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