[When the diagnosis came in Bereavement care in Germany in 2020/2021: Where do we stand?] / Als die Diagnose kam Wo steht die deutsche Trauerversorgung im Jahr 2020/2021?

BACKGROUND: In Germany, numerous health care providers work in the field of bereavement care. An epidemiological study of the field immediately after the introduction of the ICD-11 diagnosis "Prolonged Grief Disorder" (PGD) is pending. METHODS: The second survey of the trend study, which is designed over a total of three measurement points at intervals of one decade each, explores whether and to what extent the field of bereavement care has evolved after the introduction of the grief-specific diagnosis PGD. For this purpose, providers of bereavement care at various organizational levels were asked to participate in an online survey. The survey was conducted from October 2020 to January 2021. RESULTS: 456 questionnaires were included in the study. Data analysis was descriptive. 80.5% of the participants have an additional grief-specific qualification, 59.4% base their work on a grief-specific concept. In view of the PGD diagnosis, only a few respondents have participated in a PGD-related advanced training. Most are afraid that the topic of grief will increasingly be subsumed in the medical-psychological-therapeutic field. An increase in bereavement research and the number and quality of continuing education is also expected. DISCUSSION: Some positive trends in German bereavement care can be identified. However, there is a need for further development in the areas "designation of the activity", "diagnostics", and "intervention". Also, there is a need for training with regard to PGD. CONCLUSION: After the introduction of PGD, the field of bereavement care in Germany turns out to be slightly different. The diagnosis is viewed skeptically.

Case Report: Durable therapy response to Osimertinib in rare EGFR Exon 18 mutated NSCLC.

Up to 20% of all non-small cell lung cancer patients harbor tumor specific driver mutations that are effectively treated with tyrosine kinase inhibitors. However, for the rare EGFR deletion-insertion mutation of exon 18, there is very little evidence regarding the effectiveness of tyrosine kinase inhibitors. A particular challenge for clinicians in applying tyrosine kinase inhibitors is not only diagnosing a mutation but also interpreting rare mutations with unclear therapeutic significance. Thus, we present the case of a 65-year-old Caucasian male lung adenocarcinoma patient with an EGFR Exon 18 p.Glu709_Thr710delinsAsp mutation of uncertain therapeutic relevance. This patient initially received two cycles of standard platinum-based chemotherapy without any therapeutic response. After administration of Osimertinib as second line therapy, the patient showed a lasting partial remission for 12 months. Therapy related toxicities were limited to mild thrombocytopenia, which ceased after dose reduction of Osimertinib. To our knowledge, this is the first report of effective treatment of this particular mutation with Osimertinib. Hence, we would like to discuss Osimertinib as a viable treatment option in EGFR Exon 18 p.Glu709_Thr710delinsAsp mutated lung adenocarcinoma.

How Safe Do Dying People Feel at Home? Patients' Perception of Safety While Receiving Specialist Community Palliative Care.

BACKGROUND: There is a research gap regarding safety concerns of patients at the end of life. The aim of this study was, therefore, to explore whether patients under specialist community palliative care feel safe at home and which factors affect the perceived safety. Furthermore, we investigated if perception of safety is associated with different aspects of subsequent care. METHODS: Using a standardized questionnaire, a cross-sectional survey was conducted among 100 specialist community palliative care patients. Logistic regression was used to examine the strength of the association between clinical and socio-demographic variables and the perception of safety. After a 6-month follow-up period, we analyzed differences in various care-related outcomes between patients with unaffected and impaired perceptions of safety. RESULTS: In our study, one in five patients receiving specialist community palliative care expressed safety concerns. Subdomains of safety that were reported most frequently were physical disability (60%), physical symptoms (30%), psychological symptoms (26%), and side effects/complications of drug therapy (19%). Of the participants surveyed after the initial COVID-19 lockdown, 35.1% reported that they felt their safety had been adversely affected by the pandemic. Compromised safety perception was associated with higher levels of palliative care-related problems, and proximity to death. CONCLUSIONS: Our study uncovered relevant safety concerns of palliative care patients receiving specialist community palliative care. The insights gained into patient-reported problems may help healthcare professionals to identify situations where patients feel unsafe. Further research should address primary and secondary prevention measures to improve the quality of end-of-life care in the home environment.

Outpatient palliative care during the COVID-19 pandemic: a retrospective single centre analysis in Germany.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide. In Germany, patients in a palliative care setting have the opportunity to receive treatment by a specialised mobile outpatient palliative care team (OPC). The given retrospective single centre analysis describes the use of OPC structures for terminally ill COVID-19 patients during the height of the pandemic in Germany and aims to characterise this exceptional OPC patient collective. METHODS: First, death certificates were analysed in order to collect data about the place of death of all deceased COVID-19 patients (n = 471) within our local governance district. Second, we investigated whether advance care planning structures were established in local nursing homes (n = 30) during the height of the COVID-19 pandemic in 2020. Third, we examined patient characteristics of COVID-19 negative (n = 1579) and COVID-19 positive (n = 28) patients treated by our tertiary care centre guided OPC service. RESULTS: The analysis of death certificates in our local district revealed that only 2.1% of all deceased COVID-19 patients had succumbed at their home address (n = 10/471). In contrast, 34.0% of COVID-19 patients died in nursing homes (n = 160/471), whereas 63.5% died in an inpatient hospital setting (n = 299/471). A large proportion of these hospitalised patients died on non-intensive care unit wards (38.8%). Approximately 33.0% of surveyed nursing homes had a palliative care council service and 40.0% of them offered advance care planning (ACP) structures for their nursing home residents. In our two OPC collectives we observed significant differences concerning clinical characteristics such as the Index of Eastern Cooperative Oncology Group [ECOG] (p = 0.014), oncologic comorbidity (p = 0.004), as well as referrer and primary patient location (p = 0.001, p = 0.033). CONCLUSIONS: Most COVID-19 patients in our governance district died in an inpatient setting. However, the highest number of COVID-19 patients in our governance district who died in an outpatient setting passed away in nursing homes where palliative care structures should be further expanded. COVID-19 patients who died under the care of our OPC service had considerably fewer oncologic comorbidities. Finally, to relieve conventional health care structures, we propose the expansion of established OPC structures for treating terminally ill COVID-19 patients.

[Grieving in high-speed society. An acceleration-focused temporal perspective]. / Trauer in der beschleunigten Gesellschaft. Eine zeitanalytische Perspektive.

Grieving in high-speed society. An acceleration-focused temporal perspective Objectives: How long does it take the bereaved to cope with a loss of a significant other? Early findings assume weeks. Later studies speak of years. Nevertheless, the grace period for the bereaved in the modern world seems to be constantly shortening, despite objectively constant time, multiple time gains and savings. Methods: The process of acceleration described by Hartmut Rosa offers an explanation for this paradoxical disproportion. From a time-analytic perspective, it becomes clear that coping with loss runs counter to the dynamization of society. Results: Grief as a bio-psychological process cannot be accelerated as such. Instead of therapy-immanent solutions, changes are needed that are reflected on a societal level. Conclusions: The approaches 'grief literacy' and 'compassionate communities' can help to implement bereavement into the society as a whole.

Palliative care of older glioblastoma patients in neurosurgery.

PURPOSE: The care of older neurosurgical patients at the end life is a particularly demanding challenge. Especially, the specific needs of very old patients with glioblastoma at the end of life are at risk of being deprived of adequate care. METHODS: Based on a narrative literature review, this article aims to explore key issues of the thematic intersection of geriatric glioblastoma patients, palliative care and neurosurgery. RESULTS AND DISCUSSION: Four key issues were identified: patient-centeredness (need orientation and decision making), early palliative care, advance care planning, and multi-professionalism. Possible benefits and barriers are highlighted with regard to integrating these concepts into neurosurgery. CONCLUSIONS: Palliative care complements neurosurgical care of geriatric glioblastoma multiforme patients to optimise care for this highly vulnerable category of patients.

[Before the diagnosis was established A retrospective analysis of bereavement care in Germany]. / Bevor die Diagnose kam Eine Retrospektive der Trauerversorgung in Deutschland.

INTRODUCTION: In Germany, many health care providers work in bereavement care. An epidemiological study of this field of work has not yet been conducted. METHODS: In the initial survey of this three-phase trend study the situation of grief-specific health care in Germany in 2009/2010 is examined, i. e., at the time before the introduction of the new ICD-11 diagnosis of Prolonged Grief Disorder. For this purpose, bereavement care providers at different organizational levels participated in an online survey. RESULTS: 410 questionnaires were included in the study. Data analysis was descriptive. The most frequent reason for using grief-specific support services was the loss of a partner. In more than half of all cases of bereavement, people experienced a loss that was preceded by an illness and suffering. More than half of those providing bereavement care do not follow a concept of intervention. DISCUSSION: There is considerable need for further development in German bereavement care, in particular with regard to qualification and the degree of professionalization, designation of the respective interventions, diagnostics, and intervention. CONCLUSION: This three-phase trend study enables health care providers to derive bereavement care service standards that aim to treat people according to their needs. Whether the diagnosis of Prolonged Grief Disorder has led to changes in bereavement care is currently analyzed in the second survey phase of the study.

[The G-BA innovation fund's project "Avenue-Pal" - analysis and improvement of cross-sectoral and cross-departmental interface and relocation management in palliative care]. / Das G-BA-Innovationsfonds-Projekt "Avenue-Pal" : Analyse und Verbesserung des sektor- und bereichsübergreifenden Schnittstellen- und Verlegungsmanagements in der Palliativversorgung.

BACKGROUND: About 80% of all people in Germany die in inpatient care. Around every fifth person in inpatient care is relocated to another care area in the last phase of their life. That is more than 150,000 people being relocated, often without indication. 13 risk factors were identified for these non-indicated relocations. METHOD: With the support of the AWMF, two regionally effective guidelines were developed and implemented in a maximum care hospital and a care facility. A palliative consultation service has been established in the university hospital. Comprehensive personnel and organizational development was carried out in the care facility. Different collaborations with relevant regional partners of both model institutions were systematically expanded. RESULTS AND CONCLUSIONS: The relocations could be significantly reduced despite the short duration of the project. This was also possible through the establishment of decision-making aids and digital implementation support. The results of the accompanying ethical and social research justify the procedure: There is an increase in the satisfaction of relatives and employees.

The Difficulties in End-of-Life Discussions - Family Inventory (DEOLD-FI): Development and Initial Validation of a Self-Report Questionnaire in a Sample of Terminal Cancer Patients.

CONTEXT: Open end-of-life communication is especially important within the patient-family unit of care and can positively affect their medical, psychological, and relational outcomes. Nevertheless, end-of-life discussions are often perceived as difficult and avoided. OBJECTIVES: To develop and validate the Difficulties in End-of-Life Discussions - Family Inventory (DEOLD-FI) to allow a systematic assessment of reasons why people shy away from end-of-life discussions. METHODS: Patients with advanced cancer were recruited and completed the DEOLD-FI and measures of avoidance of cancer communication, quality of life and distress, and the experienced difficulty as well as the occurrence of end-of-life discussions. Standard item analyses and an exploratory factor analysis were conducted. Construct validity was analysed through associations between the DEOLD-FI and the aforementioned measures. RESULTS: Questionnaires were obtained from 112 participants (53% response rate; male 54%, mean age 64.9 years [range 33-94]). In the final 23-item version two factors were extracted: 'emotional burden due to end-of-life discussions' (α = 0.90) and "negative attitudes towards end-of-life discussions" (α = 0.91) explaining 69% of the variance (total scale α = 0.93). Construct validity was supported by its significant correlations with the reported difficulty in end-of-life discussions (r = 0.42) and avoidance of cancer communication (r = 0.40 to r = 0.46) and insignificant correlations with quality of life (r = -0.11), distress (r = 0.16), and physical well-being (r = 0.02). Those who had already engaged in end-of-life discussions showed significantly fewer communication barriers. CONCLUSION: Results provide evidence that the DEOLD-FI is a valid and reliable instrument for the assessment of difficulties in end-of-life discussions. Benefits for clinical practice and research are discussed.

Gastrointestinal Symptoms in Children With Life-Limiting Conditions Receiving Palliative Home Care.

Context: Children with life-limiting diseases suffer from gastrointestinal (GI) symptoms. Since the introduction of specialized palliative home care (SPHC) in Germany, it is possible to care for these children at home. In phase 1 of care the aim is to stabilize the patient. In phase 2, terminal support is provided. Objectives: Analysis were performed of the differences between these phases. The causes and modalities/outcome of treatment were evaluated. Methods: A retrospective study was performed from 2014 to 2020. All home visits were analyzed with regard to the abovementioned symptoms, their causes, treatment and results. Results: In total, 149 children were included (45.9% female, mean age 8.17 ± 7.67 years), and 126 patients were evaluated. GI symptoms were common in both phases. Vomiting was more common in phase 2 (59.3 vs. 27.1%; p < 0.001). After therapy, the proportion of asymptomatic children in phase 1 increased from 40.1 to 75.7%; (p < 0.001). Constipation was present in 52.3% (phase 1) and 54.1% (phase 2). After treatment, the proportion of asymptomatic patients increased from 47.3 to 75.7% in phase 1 (p < 0.001), and grade 3 constipation was reduced from 33.9 to 15% in phase 2 (p < 0.05). Conclusion: Painful GI symptoms occur in both palliative care phases but are more common in phase 2. The severity and frequency can usually be controlled at home. The study limitations were the retrospective design and small number of patients, but the study had a representative population, good data quality and a unique perspective on the reality of outpatient pediatric palliative care in Germany.

[Bereavement care in Germany: Framework for a stepped care model]. / Trauerversorgung in Deutschland. Entwurf eines gestuften Versorgungsmodells.

The loss of a loved one can have serious health implications. In Germany, however, bereavement care services often provide support regardless of risk or need. A structural framework within which these services are provided systematically and which enables the establishment of qualitative standards throughout Germany has not yet been proposed. A British stepped care model for professionalized bereavement support is actually being discussed internationally. In this paper the British model is adapted to the German context in order to improve nationwide bereavement care services.

Out-of-Hospital Emergencies in Children Under Palliative Home Care.

Introduction: Specialized palliative home care (SPHC) enables children and adolescents with life-limiting illnesses and complex needs to receive care at home. In addition to controlling symptoms and stabilizing the psychosocial situation, crisis anticipation is a component of SPHC. Since the establishment of the reporting SPHC team, parents have called for additional help from emergency medical services (EMS) in emergency situations with unexpected frequency. Children with life limiting diseases could undergo invasive procedures and unhelpful treatments with uncertain consequences. The questions arose as to which factors led to the involvement of the EMS in a palliative situation, what therapy was performed and what outcome could be reached. Methods: Records of the pediatric SPHC patients and EMS call-outs in these children of the reporting SPHC-team in the central region of Hesse, Germany (population: 1.1 million) were retrospectively analyzed from 01.11.2014 to 01.05.2021. The causes of the call-outs, the existence of an emergency agreement, the National Advisory Committee for Aeronautics (NACA) score, EMS therapy and outcome were examined. Patient data included age, palliative-justifying diagnosis, duration and intensity of care, place of death and median overall survival (MOS) and palliative SHPC treatment. Results: In total, 172 patients were analyzed during the study period. There were 27 EMS calls for a total of 20 patients/families (= EMS group). Palliative illness or a complication was the most frequent cause of call-outs. The patients in the EMS group were significantly less likely to have a DNR order, required more home visits and telephone calls and were under SPHC care for longer. There was a significantly higher proportion of crisis interventions at home visits. The children in the EMS group died less often from the underlying disease. Of the remaining 152 patients (= non-EMS group), a significantly higher proportion had a European home country. Conclusions: Despite the introduction of the SPHC, parents still call the EMS. Good cooperation and joint training should be sought to prepare all those involved for future call-outs.

Changes in Pain Medication Profile among Patients Admitted to Specialized Home Palliative Care in Relation to Referral Source: An Exploratory Study.

Pain is a common symptom leading to referrals to specialized home palliative care (SHPC) services and is known to affect patients' quality of life. To date, little is known about the impact of referral source on its management. To assess changes to pain medication profile in the course of SHPC and to identify potential differences in relation to referral source. This exploratory study is a retrospective analysis of 501 electronic medical records of a SHPC team in Germany. This included the assessment of baseline pain medication profiles according to the WHO analgesic ladder and changes to analgesic treatment in the course of SHPC with respect to referral source. At the time of admission, 77.4% of patients referred by a hospital and 78.8% of patients referred by the outpatient sector received a fixed analgesic regimen. In all, 61.9% of the inpatient group versus 62.9% of the outpatient group were treated with opioids, and 79.0% received modifications to pain medication at one point in time following admission. Thereby, patients referred by the outpatient sector received significantly earlier modifications and more supplementations of pain medication. Our study suggests positive development in the prescription of opioid analgesics compared to earlier studies in Germany. On the one hand, it highlights the relevance of thorough assessment and responsive evaluation of pain in SHPC, and on the other hand it reveals possible training needs of referring physicians, particularly those working in the outpatient sector. Our results inspired further research examining more closely the links between referral source and pain management.

[Assessing Complicated Grief: A Systematic Literature Review]. / Komplizierte Trauer erfassen: Ein systematischer Review.

OBJECTIVE: To give an overview of English and German speaking bereavement measurements for difficulties in the grieving process and complicated grief. METHOD: Systematic literature review. RESULTS: 22 measures were identified. They are categorised into general, specialized and pre-death measurements. All scales proved to have predominantly good psychometric properties. DISCUSSION: Dozens of measures of grieving have been proposed internationally. Only 3 general and 3 specialized scales are available in German language. CONCLUSION: Up to date no scale exists in German language to assess bereavement difficulties prior to death.

Targeting CREB-binding protein overrides LPS induced radioresistance in non-small cell lung cancer cell lines.

Non-small cell lung cancer (NSCLC) has a very poor prognosis even when treated with the best therapies available today often including radiation. NSCLC is frequently complicated by pulmonary infections which appear to impair prognosis as well as therapy, whereby the underlying mechanisms are still not known. It was investigated here, whether the bacterial lipopolysaccharides (LPS) might alter the tumor cell radiosensitivity. LPS were found to induce a radioresistance but solely in cells with an active TLR-4 pathway. Proteome profiling array revealed that LPS combined with irradiation resulted in a strong phosphorylation of cAMP response element-binding protein (CREB). Inhibition of CREB binding protein (CBP) by the specific inhibitor ICG-001 not only abrogated the LPS-induced radioresistance but even led to an increase in radiosensitivity. The sensitization caused by ICG-001 could be attributed to a reduction of DNA double-strand break (DSB) repair. It is shown that in NSCLC cells LPS leads to a CREB dependent radioresistance which is, however, reversible through CBP inhibition by the specific inhibitor ICG-001. These findings indicate that the combined treatment with radiation and CBP inhibition may improve survival of NSCLC patients suffering from pulmonary infections.

Lipoteichoic acids from Staphylococcus aureus stimulate proliferation of human non-small-cell lung cancer cells in vitro.

Pulmonary infections are frequent complications in lung cancer and may worsen its outcome and survival. Inflammatory mediators are suspected to promote tumor growth in non-small-cell lung cancer (NSCLC). Hence, bacterial pathogens may affect lung cancer growth by activation of inflammatory signalling. Against this background, we investigated the effect of purified lipoteichoic acids (LTA) of Staphylococcus aureus (S. aureus) on cellular proliferation and liberation of interleukin (IL)-8 in the NSCLC cell lines A549 and H226. A549 as well as H226 cells constitutively expressed TLR-2 mRNA. Even in low concentrations, LTA induced a prominent increase in cellular proliferation of A549 cells as quantified by automatic cell counting. In parallel, metabolic activity of A549 cells was enhanced. The increase in proliferation was accompanied by an increase in IL-8 mRNA expression and a dose- and time-dependent release of IL-8. Cellular proliferation as well as the release of IL-8 was dependent on specific ligation of TLR-2. Interestingly, targeting IL-8 by neutralizing antibodies completely abolished the LTA-induced proliferation of A549 cells. The pro-proliferative effect of LTA could also be reproduced in the squamous NSCLC cell line H226. In summary, LTA of S. aureus induced proliferation of NSCLC cell lines of adeno- and squamous cell carcinoma origin. Ligation of TLR-2 followed by auto- or paracrine signalling by endogenously synthesized IL-8 is centrally involved in LTA-induced tumor cell proliferation. Therefore, pulmonary infections may exert a direct pro-proliferative effect on lung cancer growth.

Interactions between neutrophils and non-small cell lung cancer cells: enhancement of tumor proliferation and inflammatory mediator synthesis.

The inflammatory tumor microenvironment plays a crucial role in tumor progression. In lung cancer, both bacterial infections and neutrophilia are associated with a poor prognosis. In this study, we characterized the effect of isolated human neutrophils on proliferation of the non-small cell lung cancer (NSCLC) cell line A549 and analyzed the impact of A549-neutrophil interactions on inflammatory mediator generation in naive and lipopolysaccharide (LPS)-exposed cell cultures. Co-incubation of A549 cells with neutrophils induced proliferation of resting and LPS-exposed A549 cells in a dose-dependent manner. In transwell-experiments, this effect was demonstrated to depend on direct cell-to-cell contact. This pro-proliferative effect of neutrophils on A549 cells could be attenuated by inhibition of neutrophil elastase activity, but not by oxygen radical neutralization. Correspondingly, neutrophil elastase secretion, but not respiratory burst, was specifically enhanced in co-cultures of A549 cells and neutrophils. Moreover, interference with COX-2 activity by indomethacin or the specific COX-2 inhibitor NS-398 also blunted the increased A549 proliferation in the presence of neutrophils. In parallel, a massive amplification of COX-2-dependent prostaglandin E2 synthesis was detected in A549-neutrophil co-cultures. These findings suggest that direct cell-cell interactions between neutrophils and tumor cells cause release of inflammatory mediators which, in turn, may enhance tumor growth in NSCLC.