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Among a group of European and Israeli ICU clinicians, perceptions of inappropriate care were frequently reported and were inversely associated with factors indicating good teamwork.

Although the effectiveness was not demonstrated, a subgroup of women treated for breast cancer can probably be supported by the program. The results of the present study are a starting point for further development and use of the program.

PurposeWhether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown.MethodsIn this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis.ResultsOf the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former.ConclusionEnhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5231-8) contains supplementary material, which is available to authorized users.

Purpose: Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of this study was to determine the relation between proteins involved in the EGFR pathway and response to (chemo)radiation and survival in a large, well-documented series of cervical cancer patients. Experimental Design: Pretreatment tissue samples of 375 consecutive International Federation of Gynecologists and Obstetricians stage Ib to IVa cervical cancer patients treated with (chemo)radiation between January 1980 and December 2006 were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. Protein expression of EGFR, phosphorylated EGFR (pEGFR), PTEN, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase (pERK) was assessed by immunohistochemistry on tissue microarrays. Results: EGFR staining was present in 35.3%, pEGFR in 19.7%, PTEN in 34.1%, phosphorylated AKT in 4.1%, and pERK in 29.2% of tumors. pEGFR staining was related to PTEN (P = 0.001) and pERK staining (P = 0.004). EGFR staining was inversely related to PTEN (P = 0.011). In multivariate analysis, membranous staining of EGFR [hazard ratio (HR), 1.84; 95% confidence interval (95% CI), 1.20-2.82; P = 0.005] and cytoplasmic staining of pEGFR (HR, 1.71; 95% CI, 1.11-2.66; P = 0.016) were independent predictors of poor response to (chemo)radiation. Membranous EGFR staining also was an independent prognostic factor for poor disease-specific survival (HR, 1.54; 95% CI, 1.09-2.17; P = 0.014). Conclusions: EGFR and pEGFR immunostainings are frequently observed and independently associated with poor response to therapy and disease-specific survival in cervical cancer patients primarily treated by (chemo)radiation. Our data present the EGFR pathway as a promising therapeutic target in already ongoing clinical trials. (Clin Cancer Res 2009;15(23):7389-97) Standard treatment of locally advanced cervical cancer has changed from radiotherapy alone to concurrent platinum-based chemoradiation. Despite this change, the 5-year survival in patients with locally advanced cervical cancer is still ∼52% (1). Currently, there are no (biological) markers available that accurately predict response to (chemo)radiation.Epidermal growth factor receptor (EGFR) is involved in the ErbB signaling pathway, which is often dysregulated in cancer. Autophosphorylation of EGFR to phosphorylated EGFR (pEGFR) leads to activation of two downstream pathways: the Ras/Raf/ mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK pathway and the phosphatidylinositol 3-kinase/ AKT pathway. PTEN (phosphatase and tensin homologue deleted on

Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)–induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)–induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.

The 32-item version of the EDMCQ might enrich the EDM climate measurement, clinicians' behaviour and the performance of healthcare organisations. This instrument offers opportunities to develop tailored ICU team interventions.

Patient-based pain educational programs may result in improvements of relevant patient-reported outcomes. However, the interventions are heterogeneous and improvement of pain was only seen in less than one third of the studies and in less than 20% of all included patients.