Geriatric palliative care: a view of its concept, challenges and strategies.

In aging societies, the last phase of people's lives changes profoundly, challenging traditional care provision in geriatric medicine and palliative care. Both specialties have to collaborate closely and geriatric palliative care (GPC) should be conceptualized as an interdisciplinary field of care and research based on the synergies of the two and an ethics of care.Major challenges characterizing the emerging field of GPC concern (1) the development of methodologically creative and ethically sound research to promote evidence-based care and teaching; (2) the promotion of responsible care and treatment decision making in the face of multiple complicating factors related to decisional capacity, communication and behavioural problems, extended disease trajectories and complex social contexts; (3) the implementation of coordinated, continuous care despite the increasing fragmentation, sectorization and specialization in health care.Exemplary strategies to address these challenges are presented: (1) GPC research could be enhanced by specific funding programs, specific patient registries and anticipatory consent procedures; (2) treatment decision making can be significantly improved using advance care planning programs that include adequate decision aids, including those that address proxies of patient who have lost decisional capacity; (3) care coordination and continuity require multiple approaches, such as care transition programs, electronic solutions, and professionals who act as key integrators.

[Provision of palliative care for people with advanced dementia]. / Palliativversorgung von Menschen mit fortgeschrittener Demenz.

As a result of a literature-based expert process, this review provides an overview about the principles of palliative care for people with advanced dementia that are relevant for clinical practice. In particular, the indications, impact and aims of palliative care for advanced dementia are described. Life-prolonging measures and management of symptoms at the end of life are discussed. Furthermore, the overview focuses on the legal basis of decision making.

Suicide and assisted dying in dementia: what we know and what we need to know. A narrative literature review.

BACKGROUND: Evidence-based data on prevalence and risk factors of suicidal intentions and behavior in dementia are as scarce as the data on assisted dying. The present literature review aimed on summarizing the current knowledge and provides a critical discussion of the results. METHODS: A systematic narrative literature review was performed using Medline, Cochrane Library, EMBASE, PSYNDEX, PSYCINFO, Sowiport, and Social Sciences Citation Index literature. RESULTS: Dementia as a whole does not appear to be a risk factor for suicide completion. Nonetheless some subgroups of patients with dementia apparently have an increased risk for suicidal behavior, such as patients with psychiatric comorbidities (particularly depression) and of younger age. Furthermore, a recent diagnosis of dementia, semantic dementia, and previous suicide attempts most probably elevate the risk for suicidal intentions and behavior. The impact of other potential risk factors, such as patient's cognitive impairment profile, behavioral disturbances, social isolation, or a biomarker based presymptomatic diagnosis has not yet been investigated. Assisted dying in dementia is rare but numbers seem to increase in regions where it is legally permitted. CONCLUSION: Most studies that had investigated the prevalence and risk factors for suicide in dementia had significant methodological limitations. Large prospective studies need to be conducted in order to evaluate risk factors for suicide and assisted suicide in patients with dementia and persons with very early or presymptomatic diagnoses of dementia. In clinical practice, known risk factors for suicide should be assessed in a standardized way so that appropriate action can be taken when necessary.

Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care.

OBJECTIVE: The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. METHODS: Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. RESULTS: At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 ± 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. CONCLUSIONS: Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright © 2016 John Wiley & Sons, Ltd.

Decision making at the end of life--cancer patients' and their caregivers' views on artificial nutrition and hydration.

PURPOSE: Deciding on artificial nutrition and hydration (ANH) at the end of life (EoL) may cause concerns in patients and their family caregivers but there is scarce evidence regarding their preferences. Therefore, the aim of this study was to assess the impact of factors associated with ANH decision making. METHODS: Prospective, Cross-sectional survey. Adult patients admitted to hospital for symptoms of advanced cancer as well as their family caregivers completed a self-administered questionnaire. Items included personal views and concerns about ANH. Family caregivers additionally recorded their preference for their loved one and, if applicable, previous experience with ANH decisions. RESULTS: Thirty-nine out of sixty-five patients and 30/72 relatives responded. Higher age of the patient was significantly correlated with both the patient's and the relative's decision to forgo ANH (Kruskal-Wallis test, p < 0.01). Thirty-nine percent of patients, 37 % of relatives if deciding for themselves, and 24 % of relatives if deciding on behalf of their loved one opted against ANH; 36, 40 and 52 % preferred artificial hydration (AH) only (χ (2) test, p <0.001), while 23, 23 and 24 %, respectively, wished to receive ANH. Patients felt more confident about decisions on artificial nutrition (AN) than caregivers (T test, p < 0.05) and less concerned about adverse effects of forgoing ANH on pain, agitation and sensation of hunger and thirst (χ (2) test, p < 0.05). Satisfaction of patients with communication regarding forgoing ANH (5.0 ± 2.8 on a Likert scale from 0 to 10) correlated with their confidence (Spearman's rho, p < 0.01). A thorough consultation with the attending physician on ANH issues was the favoured source of support for 77 % of patients and 97 % of relatives. A majority of patients considered their relatives' opinion (67 %) and their own advance directives (62 %) as crucial for making ANH decisions, and 46 % of them had such a document completed. CONCLUSION: Cancer patients and their relatives have similar preferences regarding ANH at the EoL, but relatives are reluctant to withhold AH if deciding for their loved one. While patients seem to be confident with ANH decision making, their caregivers may particularly benefit from discussing ANH options to dissipate fears.

[Changing the therapeutic goal in critically ill patients. Ethical analysis of a surgical case]. / Änderung des Therapieziels bei kritisch Kranken. Ethische Analyse eines chirurgischen Falles.

We report on a 32-year-old patient, who developed septic shock, toxic shock-like syndrome, and multiple organ failure following nectrotizing fasciitis. Amputations had to be performed on all extremities. Subsequently, she developed secondary sclerosing cholangitis. Treatment goals had to be reassessed, since long-term survival seemed doubtful and, in the best case, burdened with severe handicap. We discuss the evaluation of the treatment goals, utilizing a structured model of goal-setting. In the first step the treatment goal is identified based on the patient's wishes. This goal's realistic achievability is verified considering scientific evidence and medical experience. The benefit of the aspired goal is set in relation to risks and burden of the necessary treatment measures in a third step. The resulting benefit-risk ratio must be evaluated by the patient or her representative. Treatment goals have to be reevaluated if the assessment of achievability or the benefit-risk ratio are disadvantageous. In this case, the initial therapeutic goal was retained. After an extraordinarily prolonged and complex therapy including reconstructive surgery the patient is now living independently at home.

[Prophylaxis and therapy of post-traumatic stress disorder with propranolol: evidence and ethical analysis]. / Prophylaxe und Therapie der posttraumatischen Belastungsstörung mit Propranolol : Evidenz und ethische Analyse.

The beta-antagonistic agent propranolol is increasingly being used in clinical trials for the prophylaxis and treatment of post-traumatic stress disorder (PTSD). This article discusses the evidence for the effectiveness of propranolol in the prophylaxis and treatment of PTSD and the ethical implications of research on these treatment approaches. The efficacy of a prophylactic or therapeutic use could not be shown during the last decade. Both treatment approaches raise ethical questions that should already be addressed during the clinical trials.

[Changing the treatment goal at the end of life: effects of a guideline at a hospital]. / Änderung des Therapieziels am Lebensende: Effekte einer Klinik-Leitlinie.

BACKGROUND AND OBJECTIVE: Deciding about treatment goals at the end of life is a frequent and difficult challenge to medical staff. As more health care institutions issue ethico-legal guidelines to their staff the effects of such a guideline should be investigated in a pilot project. PARTICIPANTS AND METHODS: Prospective evaluation study using the pre-post method. Physicians and nurses working in ten intensive care units of a university medical center in Germany answered a specially designed questionnaire before and one year after issuance of the guideline. RESULTS: 197 analyzable answers were obtained from the first (pre-guideline) and 251 from the second (post-guideline) survey (54 % and 58 % response rate, respectively). Initially the clinicians expressed their need for guidelines, advice on ethical problems, and continuing education. One year after introduction of the guideline one third of the clinicians was familiar with the guideline's content and another third was aware of its existence. 90% of those who knew the document welcomed it. Explanation of the legal aspects was seen as its most useful element. The pre- and post-guideline comparison demonstrated that uncertainty in decision making and fear of legal consequences were reduced, while knowledge of legal aspects and the value given to advance directives increased. The residents had derived the greatest benefit. CONCLUSION: By promoting the knowledge of legal aspects and ethical considerations, guidelines given to medical staff can lead to more certainty when making in end of life decision.

[Best interests in the 'vegetative state']. / Ärztliche Indikation beim "Wachkoma".

Treatment decisions for patients in the vegetative state often have to be based on the patient's best interests, if the patient's will is not known. Physicians are, however, highly uncertain what kind of treatment is in such a difficult situation the patient's best interests. This article presents new insights from neuroscience and shows how treatment decision making should proceed to reach an ethically justified decision. Pivotal elements are a careful diagnosis using validated behavioural scales, an informed judgment about the existence of awareness and sentience, and an early prognostic assessment. As new imaging techniques and treatment options are not yet clinical standard due to low evidence, the best interests have to be judged in the context of uncertainty. The leading question should be whether the preferred treatment goal can be achieved with a realistic probability and a justifiable benefit-harm-ratio. This has to be judged for the individual patient, considering his personality and communicating with the family members. There cannot be a general answer to the question of best interests in the vegetative state, but only an individual answer in shared responsibility and based on the particular features of a special case.

A new law on advance directives in Germany.

This article presents the new German law on advance directives from 1 September 2009. The history of the parliamentary process of this law is described, the present regulations are explained, their relevance for medical practice discussed and shortcomings are identified. Finally, the new law is compared with other regulations in the international context. Previously established legal practice in Germany has now become largely confirmed by the new law: An advanced directive must be respected in any decision concerning medical treatment, regardless of the stage of the illness. It can be informally revoked at any time, even with limited decision-making capacity. Nobody may be obliged to issue a directive in any way. Advance directives do not need notarisation or routine updating after certain time intervals. Provided that the patient, who is no longer mentally competent, has issued a lasting power of attorney (Bevollmächtiger), or provided that the patient has been appointed a healthcare proxy by the courts (Betreuer), this authorized surrogate must assert the patient's will. The role of the guardianship court is clarified: it only needs to be involved in cases of disagreement as to the patient's will. The new German law thus combines more legal certainty with a liberal emphasis on patient autonomy and flexible, adaptable regulations.

[End-of-life decisions, powers of attorney, and advance directives]. / Entscheidungen am Lebensende, Vorsorgevollmacht und Patientenverfügung.

In modern medicine, decisions about the kind of treatment at life's end are often inevitable. According to German law, powers of attorney and advance directives can be of help in these decisions. When a patient in a state of competence has issued a lasting power of attorney, there is no need for courts to appoint a proxy, and physicians immediately have a legally empowered decision-maker they can address. According to current German law, advance directives are legally valid and binding expressions of a patient's will. They are, however, more powerful when issued after consultation with a physician. If treatment at life's end no longer complies with the patient's will or loses its medical indication, the goal of treatment should be redirected towards palliation. This implies that life-sustaining treatment may be withdrawn or withheld, which is best accomplished with sensitivity to the needs of patients, relatives, and health care professionals.

Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN.

Inhibition of bcl-2 expression by antisense oligodeoxynucleotides (ODN) might render bcl-2 overexpressing malignant B cells more susceptible to chemotherapy. ODN containing unmethylated CG dinucleotides (CpG) are known to activate B cells. We studied the effects of two bcl-2 antisense ODN, with (G3139) or without CG dinucleotides (NOV 2009) within the sequence, and the effects of a nonantisense, CpG-containing ODN (ODN 2006) on activation and apoptosis of malignant B cell lines and primary B-CLL cells. Without cationic lipids, no antisense-mediated inhibition of bcl-2 synthesis was achieved with G3139 and NOV 2009. Instead, G3139, but not NOV 2009, induced similar changes as ODN 2006 in proliferation, expression of costimulatory and antigen-presenting molecules, as well as in bcl-2 and bcl-xL levels of primary B-CLL cells. G3139 and ODN 2006 inhibited in vitro, spontaneous apoptosis in B-CLL cells of patients with high serum thymidine kinase activity (s-TK, marker for proliferative activity of malignant B cells), whereas in patients with low s-TK activity, apoptosis was induced. In conclusion, our results suggest that modulation of malignant B cell apoptosis by G3139 depends on its immunostimulatory properties rather than on antisense-mediated reduction of bcl-2 expression. Immunostimulatory CpG ODN may have a therapeutic potential in patients with B-CLL, especially those with low s-TK activity.

Shock waves: a novel method for cytoplasmic delivery of antisense oligonucleotides.

Intracytoplasmic delivery of oligonucleotides (ODN) can improve ODN-based strategies such as the antisense approach and the use of immunostimulatory CpG dinucleotide containing ODN. Shock waves are established for the treatment of nephrolithiasis and other diseases. Here we describe the use of shock waves as a new physical method for the direct transport of antisense ODN into the cytoplasm and the nucleus of cells. Human peripheral blood mononuclear cells together with antisense ODN were exposed to shock waves generated by an electrohydraulic lithotripter. ODN uptake was examined by flow cytometry and fluorescence microscopy. By optimization of physical parameters we achieved the transfer of high amounts of ODN which were detected within less than 5 min after shock wave exposure, with viability of cells higher than 95%. Transfection of human peripheral blood mononuclear cells with an antisense ODN directed against tumor necrosis factor (TNF) alpha resulted in a reduction in lipopolysaccharide-induced TNF production by 62% (n=5, P=0.006). Specificity of TNF suppression was confirmed with a four-mismatch oligonucleotide. Positive atmospheric pressure abolished antisense-mediated inhibition of TNF synthesis by blocking shock wave-induced cavitation and formation of oscillating air bubbles. Electroporation was less effective. The use of shock waves is thus an efficient physical tool for ODN delivery to cells. Shock waves may allow the evaluation of target proteins in cell types difficult to transfect with other methods and thus may improve the antisense technique for the analysis of unknown genes.