Assisted Peritoneal Dialysis for Older People with End-Stage Renal Disease: The French and Danish Experience

Older people are the largest and fastest growing group of patients with end-stage renal disease (ESRD), and, due to advanced age and a heavy burden of comorbidities, they are usually not candidates for renal transplantation or home-based dialysis treatment. Some of the barriers for home treatment are non-modifiable, but the majority of physical disabilities and psychosocial problems can be overcome provided that assistance is offered to the patients at home.In the present review, we describe the programs for assisted peritoneal dialysis (PD) in France and Denmark, respectively. In both nations, assisted PD is totally publicly funded, and the cost of assisted PD is comparable to the cost of in-center HD. Assisted continuous ambulatory PD (aCAPD) is the preferred modality in France whereas assisted automated PD (aAPD) is the preferred modality in Denmark. Assistants are professional nurses or healthcare technicians briefly educated by expert PD nurses from the dialysis unit.The establishment of a program for assisted PD may increase the number of patients actually treated with PD and may reduce the risk of PD technique failure and prolong PD duration. Compared with autonomous PD patients, patients on assisted PD may have shorter patient survival and peritonitis-free survival indicating that, besides advanced age and the burden of comorbidities, dependency on help may be an independent risk factor for poorer outcome.Assisted PD is an evolving dialysis modality, and may in the future prove to be a feasible complementary alternative to in-center hemodialysis (HD) for the growing group of dependent older patients with ESRD.     

Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8⁺ tumours formed multiple liver and spleen metastases, while Tspan8⁻ tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up-regulation of E-cadherin and down-regulation of Twist, p120-catenin, and β-catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8⁺ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several-fold increase in EV number in cell culture and the circulation of tumour-bearing animals. We observed increased protein levels of E-cadherin and p120-catenin in these EVs; furthermore, Tspan8 and p120-catenin were co-immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Vorsorgedokumente in der präklinischen Notfallmedizin

Background

The handling of advance directives (AD) in prehospital emergency treatment in Germany is characterized by instability. In the project “Advance directives in preclinical emergency medical aid” (“Patientenverfügungen in der präklinischen Notfallmedizin”) the frequency and quality of ADs in emergency situations was investigated.

Aim

The aim of this study was to fill the gaps in research and to collate data on how consideration of the self-determination of patients in emergency situations can be optimized.

Material and methods

Over a period of 12 months from December 2007 to December 2008 a questionnaire was included in the emergency documentation of the medical emergency service in Aachen. Emergency patients were asked by emergency physicians to provide an AD and the quantitative as well as qualitative features of these ADs were examined. Furthermore, the study recorded what kinds of problems occurred with ADs in emergency situations and what measures were needed to correct this deficiency. The reactions of patients were documented on a numeral rating scale with a score of 1 reflecting a negative and 10 reflecting a positive reaction. In the 12-month period emergency doctors recorded 1,321 missions and after application of the exclusion criteria (e.g. missing signature, incomplete documentation and late delivery) 1,047 documented questionnaires were available for the analysis.

Results

A total of 127 out of 1,047 emergency patients provided an AD, 44 had a durable power of attorney and 27 had appointed a legal representative for healthcare. Of the emergency patients 20 had a legal attendant and 43 out of the 127 ADs could be presented to the emergency team during the emergency mission. The emergency team often encountered difficulties regarding the handling of the ADs due to the time factor and unclear wording. The latter included the following problems: misleading formulation (19.1?%), difficulty with the complexity (14.9?%) and contradicting information (4?%). Only 29 (61.7?%) of the durable powers of attorney were signed and legally binding. From the view of the emergency physicians the following information was lacking but would be helpful in emergency situations: emergency plan, hierarchy of those given power of attorney, knowledge of risks regarding ADs and medication requirements.

Conclusion

The results show that for an AD to apply in an emergency situation certain standards are necessary that assure the practicability, especially if a patient does not wish to be resuscitated. Most difficulties with ADs occurred with imprecise formulation, text length and inconsistency of statements. The following instructions were usually missing: hierarchy of those given power of attorney and specification on medication, information about the scope of the ADs, statement about resuscitation, extent and limitations of the desired treatment, especially with patients certified as terminally ill and instructions on who should decide about medical treatment in a conflict situation. A so-called emergency instruction which gives on a single page the patient’s statement on resuscitation would have been very helpful in individual cases. The results suggest that patients may need more information and education about AD to guarantee patients rights and self-determination.     

Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration

Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, we evaluated single-dose digoxin kinetics along with repeated measurements of intraerythrocytic sodium concentration in eight healthy subjects before and during verapamil coadministration. Verapamil reduced mean total body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg and prolonged digoxin biologic t1/2 from 33.5 +/- 2.4 to 41.4 +/- 2.3 hr. These kinetic changes were associated with a greater elevation of intraerythrocytic sodium concentration than controls. Verapamil had no effect on intraerythrocytic sodium content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular sodium concentration has proved to correlate closely with clinical signs of digoxin toxicity, our indicate that verapamil is likely to increase the risk of digoxin-induced arrhythmias.