Determinants of completion of advance directives: a cross-sectional comparison of 649 outpatients from private practices versus 2158 outpatients from a university clinic.

OBJECTIVES: To compare outpatients from private practices and outpatients from a university clinic regarding the determinants of completion of advance directives (AD) in order to generalise results of studies from one setting to the other. Five determinants of completion of AD were studied: familiarity with AD, source of information about AD, prior experiences with own life-threatening diseases or family members in need of care and motives in favour and against completion of AD. DESIGN: Observational cross-sectional study. SETTING: Private practices and a university clinic in Germany in 2012. PARTICIPANTS: 649 outpatients from private practices and 2158 outpatients from 10 departments of a university clinic. OUTCOME MEASURES: Completion of AD, familiarity with AD, sources of information about AD (consultation), prior experiences (with own life-threatening disease and family members in need of care), motives in favour of or against completion of AD, sociodemographic data. RESULTS: Determinants of completion of AD did not differ between outpatients from private practices versus university clinic outpatients. Prior experience with severe disease led to a significantly higher rate of completion of AD (33%/36% with vs 24%/24% without prior experience). Participants with completion of AD had more often received legal than medical consultation before completion, but participants without completion of AD are rather aiming for medical consultation. The motives in favour of or against completion of AD indicated inconsistent patterns. CONCLUSIONS: Determinants of completion of AD are comparable in outpatients from private practices and outpatients from a university clinic. Generalisations from university clinic samples towards a broader context thus seem to be legitimate. Only one-third of patients with prior experience with own life-threatening diseases or family members in need of care had completed an AD as expression of their autonomous volition. The participants' motives for or against completion of AD indicate that ADs are considered a kind of 'negative autonomy' as instruments to prevent particular forms of therapy. Interactive, repeated and situation-based AD discussions might reach a higher percentage of patients and concurrently enable personal volitions and thereby strengthen individual 'positive autonomy'.

Complementary and Alternative Medicine: A Clinical Study in 1,016 Hematology/Oncology Patients.

INTRODUCTION: Surveys state a widespread use of complementary and alternative medicine (CAM) in patients with malignant diseases. CAM methods might potentially interfere with the metabolization of tumor-specific therapy. However, there is little communication about CAM use in hematology/oncology patients between patients, CAM providers, and oncologists. PATIENTS AND METHODS: A self-administered questionnaire was handed out to all patients attending to the hematology/oncology outpatient clinic of Regensburg University Hospital. Subsequently, a chart review of all CAM users was performed. RESULTS: Questionnaires of 1,016 patients were analyzed. Of these patients, 30% used CAM, preferably vitamins and micronutrients. Main information sources for CAM methods were physicians/nonmedical practitioners and friends/relatives. CAM therapies were provided mainly by licensed physicians (29%), followed by nonmedical practitioners (14%) and the patients themselves (13%). Although 62% of the CAM users agreed that the oncologist may know about their CAM therapy, a chart entry about CAM use was found only in 41%. CONCLUSION: CAM is frequently used by hematology/oncology patients. Systematic communication about CAM is essential to avoid possible drug interactions.

The impact of a tumor diagnosis on patients' attitudes toward advance directives.

BACKGROUND: Although advance care planning and the completion of advance directives (ADs) are important tools to avoid unwanted aggressive care once patients have lost their decision-making capacity, only a minority of cancer patients are admitted with completed ADs, and little is known about patients' wishes regarding AD consultations. METHODS: For 1 year, every new patient admitted to the hematology/oncology outpatient clinic of the University Hospital Regensburg received a self-administered questionnaire comprising a self-evaluation of AD knowledge and questions about preferences regarding consultation partners and the time of consultation. Disease-related data were collected from medical records. Statistics were calculated with SPSS. RESULTS: Of the 500 questionnaires handed out, 394 (75%) were evaluable and analyzed. Twenty-eight percent of the participants had completed an AD (living will or health care proxy). Ninety-two percent of the participants without ADs had never received a consultation offer from any professional involved. Only 20% perceived a clear relation between cancer and AD consultations. More than 50% of the participants without ADs were in favor of consultations 'now' or 'in a few weeks', while more than 40% objected to AD consultations. CONCLUSIONS: Oncology patients have a large unmet demand for AD consultations. However, a relevant percentage of these patients object to AD consultations. Structured and early AD consultation offers should be made, and early discussions about indications for aggressive treatment should take place.

Prehospital emergency treatment of palliative care patients with cardiac arrest: a retrolective investigation.

BACKGROUND: Today, prehospital emergency medical teams (EMTs) are confronted with emergent situations of cardiac arrest in palliative care patients. However, little is known about the out-of-hospital approach in this situation and the long-term survival rate of this specific patient type. The aim of the present investigation was to provide information about the strategic and therapeutic approach employed by EMTs in outpatient palliative care patients in cardiac arrest. METHODS: During a period of 2 years, we retrolectively analysed emergency medical calls with regard to palliative care emergency situations dealing with cardiac arrest. We evaluated the numbers of patients who were resuscitated, the prevalence of an advance directive or other end-of-life protocol, the first responder on cardiac arrest, the return of spontaneous circulation (ROSC) and the survival rate. RESULTS: Eighty-eight palliative care patients in cardiac arrest were analysed. In 19 patients (22%), no resuscitation was started. Paramedics and prehospital emergency physicians began resuscitation in 61 cases (69%) and in 8 cases (9%), respectively. A total of 10 patients (11%) showed a ROSC; none survived after 48 h. Advance directives were available in 43% of cases. The start of resuscitation was independent of the presence of an advance directive or other end-of-life protocol. CONCLUSIONS: Strategic and therapeutic approaches in outpatient palliative care patients with cardiac arrest differ depending on medical qualification. Although many of these patients do not wish to be resuscitated, resuscitation was started independent of the presence of advance directive. To reduce legal insecurity and to avoid resuscitation and a possible lengthening of the dying process, advance directives and/or "Do not attempt resuscitation" orders should be more readily available and should be adhered to more closely.

Preferential targeting of CD4-CCR5 complexes with bifunctional inhibitors: a novel approach to block HIV-1 infection.

Two receptors, CD4 and one of several chemokine receptors, are required for cellular HIV-1 infection, with CCR5 being the main coreceptor for macrophage-tropic strains. We have designed bifunctional fusion proteins, consisting of RANTES/CCL5 and a single-chain Fv Ab fragment against CD4 to simultaneously block CD4 and CCR5. The fusion proteins bind to both receptors, compete with RANTES/CCL5 binding, and induce down-modulation of CCR5 approximately 10 times more efficiently on CD4+ compared with CD8+ T cells. Moreover, after short incubation and subsequent washout, a significant down-modulation of CCR5 was only seen with the fusion proteins and only on CD4+ cells, but not with unmodified RANTES or on CD4- cells, indicating a preferential targeting of CCR5 on CD4+ T cells. The fusion proteins block M-tropic HIV infection more efficiently than RANTES/CCL5 and CD4 Abs alone or in combination. To our knowledge this is the first report of simultaneous blockade of an HIV-1 receptor and coreceptor with bifunctional inhibitors.

Roles of SLC/CCL21 and CCR7 in human kidney for mesangial proliferation, migration, apoptosis, and tissue homeostasis.

The release of chemokines by intrinsic renal cells is an important mechanism for the regulation of leukocyte trafficking during renal inflammation. The expression of chemokine receptors by intrinsic renal cells such as mesangial cells (MC) suggests an expanded role for chemokine-chemokine receptor biology in local immunomodulation and potentially glomerular homeostasis. By immunohistochemistry we found the chemokine receptor CCR7 expressed in a mesangial pattern while the CCR7 ligand SLC/CCL21 showed a podocyte-specific expression. CCR7 expression was further characterized by RT-PCR, RNase protection assays, and FACS analysis of cultured human MC, and was found to be constitutively present. Real-time PCR of microdissected glomeruli confirmed the expression of SLC/CCL21. A functional role for CCR7 was demonstrated for human MC migration and proliferation. A protective effect of SLC/CCL21 was shown for MC survival in Fas Ab-induced apoptosis. Finally, "wound healing" was enhanced in the presence of SLC/CCL21 in an in vitro injury model. The constitutive glomerular expression of CCR7 and its ligand SLC/CCL21 in adjacent cell types of the human kidney suggests novel biological functions of this chemokine/chemokine receptor pair and a potential role in processes involved in glomerular homeostasis and regeneration.

Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes.

The sequestration of chemokines on the surface of microvascular endothelium is an early event in the selective recruitment of leukocytes. The sequestration and presentation of chemokines must be tightly controlled to confine the extravasation of leukocytes and to prevent uncontrolled inflammation. We investigated whether soluble molecules released under physiological conditions could control chemokine immobilization on cell surfaces and function as regulatory chemokine binding molecules. We determined that human serum contains a molecule that suppresses RANTES (CCL5) binding to endothelial cells, PBMC and CHO cells. Using platelet-rich and platelet-free plasma, serum from patients with thrombocytopenia, and purified platelets, we identified platelets as the source of the chemokine-binding molecule and further identified it as chondroitin sulfate A. In contrast to platelet-derived fully-sulfated chondroitin sulfate A, low-sulfated chondroitin sulfate A present in plasma was almost inactive. Under physiological flow conditions chondroitin sulfate A was found to block RANTES-mediated firm adhesion of monocytes to endothelial cells. It also prevented RANTES-mediated influx of calcium in CCR5-transfected CHO cells while internalization of CCR5 was only marginally reduced. Taken together, chondroitin sulfate A released from platelets appears to act as an important regulatory molecule for cellular responses to chemokines.