Pharmacological treatment of cancer pain and opioid induced nausea and vomiting: online survey and comparison with current guidelines.

PURPOSE: We assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice of pharmaceutical treatment choices of physicians for cancer pain and opioid-induced nausea and vomiting (OINV) and the rationale for their choices. METHODS: An online survey was conducted with physicians covering the following domains: i) Cancer pain therapy: non-opioids in addition to opioids: choice of drug ii) prevention of OINV: choice of drug and mode of application. Current guidelines concerning cancer pain therapy and prevention of OINV were compared. RESULTS: Two-hundred-forty European physicians responded to our survey. i) Use of non-opioids in addition to opioids for the treatment of cancer pain: Only 1.3% (n = 3) of respondents never used an additional non-opioid. Others mostly used: dipyrone/metamizole (49.2%, n = 118), paracetamol/acetaminophen (34.2%, n = 82), ibuprofen / other NSAIDs (11.3%, n = 27), specific Cox2-inhibitors (2.1%, n = 5), Aspirin (0.4%, n = 1), no answer (2.9%, n = 7). ii) Antiemetics to prevent OINV: The drugs of choice were metoclopramide (58.3%, n = 140), haloperidol (26.3%, n = 63), 5-HT3 antagonists (9.6%, n = 23), antihistamines (1.3%, n = 3) and other (2.9%, n = 7); no answer (1.7%, n = 4). Most respondents prescribed the substances on-demand (59.6%, n = 143) while others (36.3%, n = 87) provided them as around the clock medication. Over both domains, most physicians answered that their choices were not based on solid evidence from randomized controlled trials (RCTs). Guidelines were inconsistent regarding if and what non-opioid to use for cancer pain and recommend anti-dopaminergic drugs for prevention or treatment of OINV. CONCLUSIONS: Physician's practice in palliative care for the treatment of cancer pain and OINV differed substantially. Respondents expressed the lack of high-quality evidence- based information from RCTs. We call for evidence from methodologically high-quality RCTs to be available to inform physicians about the benefits and harms of pharmacological treatments for common symptoms in palliative care.

Systemic Anticancer Treatment Near the End of Life: a Narrative Literature Review.

OPINION STATEMENT: Systemic anticancer therapy (SACT) includes different treatment modalities that can be effective in treating cancer. However, in the case of disease progression, cancers might become incurable and SACT might reach its limits. In the case of incurable cancers, SACT is often given in a palliative setting, with the goal of improving the patients' quality of life (QOL) and their survival. In contrast, especially for patients who approach end of life (EOL), such treatments might do more harm than good. Patients receiving EOL anticancer treatments often experience belated palliative care referrals. The use of systemic chemotherapy in patients with advanced cancer and poor prognosis approaching the EOL has been associated with significant toxicity and worse QOL compared to best supportive care. Therefore, the American Society of Clinical Oncology (ASCO) has discouraged this practice, and it is considered a metric of low-value care by Choosing Wisely (Schnipper et al. in J Clin Oncol 4;30(14):1715-24). Recommendations of the European Society for Medical Oncology (ESMO) suggest that especially chemotherapy and immunotherapy should be avoided in the last few weeks of the patients' lives. In this narrative review, we screened the current literature for the impact of SACT and factors predicting the use of SACT near the EOL with discussion on this topic.

Evaluation of diagnostic and treatment approaches to acute dyspnea in a palliative care setting among medical doctors with different educational levels.

BACKGROUND: Dyspnea is common in patients with advanced cancer. Diagnostic procedures in patients with dyspnea are mandatory but often time-consuming and hamper rapid treatment of the underlying refractory symptoms. Opioids are the first-line drugs for the treatment of refractory dyspnea in palliative care patients with advanced lung cancer. METHODS: To evaluate the knowledge levels of medical doctors with different educational levels on the diagnosis of and treatment options for dyspnea in patients with advanced lung cancer in a palliative care setting, a case report and survey were distributed to physicians at the University Hospital Krems, describing acute dyspnea in a 64-year-old stage IV lung cancer patient. A total of 18 diagnostic and 22 therapeutic options were included in the survey. The physicians were asked to suggest and rank in order of preference their diagnosis and treatment options. Statistical analyses of the data were performed, including comparison of the responses of the senior doctors and the physicians in training. RESULTS: A total of 106 surveys were completed. The respondents were 82 senior physicians and 24 physicians in training (response rates of 86% and 80%, respectively). Regarding diagnostic investigations, inspection and reading the patient's chart were the most important diagnostic tools chosen by the respondents. The choices of performing blood gas analysis (p = 0.01) and measurement of oxygen saturation (p = 0.048) revealed a significant difference between the groups, both investigations performed more frequently by the physicians in training. As for non-pharmacological treatment options, providing psychological support was one of the most relevant options selected. A significant difference was seen in choosing the option of improving a patient's position in relation to level of training (65.9% senior physicians vs. 30.4% physicians in training, p = 0.04). Regarding pharmacological treatment options, oxygen application was the most chosen approach. The second most frequent drug chosen was a ß-2 agonist. Only 9.8% of the senior physicians and 8.7% of the physicians in training suggested oral opioids as a treatment option, whereas intravenous opioids were suggested by 43.9% of the senior physicians and 21.7% of the physicians in training (p = 0.089). For subcutaneous application of opioids, the percentage of usage was significantly higher for the physicians in training than for the senior physicians (78.3% vs. 48.8%, p = 0.017, respectively). CONCLUSION: The gold standard treatment for treating refractory dyspnea in patients with advanced lung cancer is opioids. Nevertheless, this pharmacological treatment option was not ranked as the most important. Discussing hypothetical cases of patients with advanced lung cancer and refractory dyspnea with experienced doctors as well as doctors at the beginning of their training may help improve symptom control for these patients.

Autoimmunity in Acute Myocarditis: How Immunopathogenesis Steers New Directions for Diagnosis and Treatment.

PURPOSE OF REVIEW: Over the last decade, myocarditis has been increasingly recognized as common cause of sudden cardiac death in young adults and heart failure overall. The purpose of this review is to discuss hypothesis of development of non-infectious myocarditis, to provide a description of the immunopathogenesis and the most common mechanisms of autoimmunity in myocarditis, and to provide an update on therapeutic options. RECENT FINDINGS: A new entity of myocarditis is immune checkpoint inhibitor (ICI) induced myocarditis. ICIs are used in advanced cancer to "disinhibit" the immune system and make it more aggressive in fighting cancer. This novel drug class has doubled life expectancy in metastatic melanoma and significantly increased progression free survival in advanced non-small-cell lung cancer, but comes with a risk of autoimmune diseases such as myocarditis resulting from an overly aggressive immune system. Myocarditis is an inflammatory disease of the heart with major public health impact. Thorough understanding of its immunopathogenesis is crucial for accurate diagnosis and effective treatment.

Symptomatic treatment of dyspnea in advanced cancer patients : A narrative review of the current literature.

BACKGROUND: Dyspnea is a common, very distressing symptom in advanced cancer patients that challenges them, their relatives, and healthcare professionals. This narrative review summarizes important literature dealing with the evidence for opioids, benzodiazepines, oxygen, and steroids for treating dyspnea in advanced cancer patients. METHODS: A selective literature search was undertaken in PubMed, Embase, and the Cochrane Library and extended with literature from the reference lists of included studies up to April 2016. Inclusion criteria were that patients were suffering from advanced cancer and were receiving either opioids, benzodiazepines, corticosteroids, or oxygen. The outcome of interest was the reduction of dyspnea measured via a visual analogue scale (VAS), a numerical rating scale (NRS), or a Borg scale. This narrative review describes in detail the findings of 13 studies. RESULTS: Nine studies deal with the effectiveness of opioids for reducing dyspnea in advanced cancer patients. Five of these found a significant benefit to the use of opioids compared to a placebo. Three found no significant improvements, and two favored combinations of opioids and benzodiazepines. Few high-quality studies were available that used benzodiazepines (n = 3, no difference, significant improvement with midazolam + morphine, significant difference for midazolam) or oxygen (n = 2, both without significant difference). Only one study examined treating dyspnea with steroids in patients with advanced cancer, and that study indicated a benefit of steroids compared to a placebo. CONCLUSIONS: Opioids are the drug of choice for treating refractory dyspnea in advanced cancer patients. Neither benzodiazepines nor oxygen showed significant benefit. In addition, there is insufficient literature available to draw a conclusion about the effectiveness of steroids for treating persistent dyspnea in advanced cancer patients.

Methadone as anticancer treatment: hype, hope, or hazard? : A series of case reports and a short review of the current literature and recommendations of the societies.

Recently, the use of methadone in cancer patients has increased due to in vitro studies indicating that methadone is capable of inducing cell death. However, thus far there are no relevant clinical studies indicating that the use of methadone can prolong survival in cancer patients. Based on low-quality evidence, methadone is a drug that has similar analgesic benefits to morphine and has a role in the management of cancer pain in adults. Other opioids such as morphine, hydromorphone, and fentanyl are easier to manage but may be more expensive than methadone in many economies. Methadone is an opioid that is only approved for replacement therapy in Austria. Methadone can be used as a second- or third-line agent for severe cancer-related pain, but its use should be restricted to experts. Here we report a series of cases of patients who developed problems when using methadone as an antitumor treatment, with a brief review on the role of methadone as a pain medication and the current lack of value as an anti-tumor therapy. Methadone is not approved or recommended as an anticancer treatment in Austria or Germany. The Austrian Association for Hemato-oncology (OeGHO), the Austrian Association for the Management of Pain (ÖSG), and the Austrian Association for Palliative Care (OPG) do not recommend the use of methadone as an anticancer treatment. Thus, from a medical and ethical point of view, the use of methadone as an antitumor therapy is to be rejected, based on the views of various Austrian (OeGHO, ÖSG, OPG) and German specialists. Unqualified use of methadone by nonexperienced pain therapists is dangerous and must also be rejected.

Sedation at the end of life - a nation-wide study in palliative care units in Austria.

BACKGROUND: Sedation is used to an increasing extent in end-of-life care. Definitions and indications in this field are based on expert opinions and case series. Little is known about this practice at palliative care units in Austria. METHODS: Patients who died in Austrian palliative care units between June 2012 and June 2013 were identified. A predefined set of baseline characteristics and information on sedation during the last two weeks before death were obtained by reviewing the patients' charts. RESULTS: The data of 2414 patients from 23 palliative care units were available for analysis. Five hundred two (21 %) patients received sedation in the last two weeks preceding their death, 356 (71 %) received continuous sedation until death, and 119 (24 %) received intermittent sedation. The median duration of sedation was 48 h (IQR 10-72 h); 168 patients (34 %) were sedated for less than 24 h. Indications for sedation were delirium (51 %), existential distress (32 %), dyspnea (30 %), and pain (20 %). Midazolam was the most frequently used drug (79 %), followed by lorazepam (13 %), and haloperidol (10 %). Sedated patients were significantly younger (median age 67 years vs. 74 years, p ≤ 0.001, r = 0.22), suffered more often from an oncological disease (92 % vs. 82 %, p ≤ 0.001, φ = 0.107), and were hospitalized more frequently (94 % vs. 76 %, p ≤ 0.001, φ = 0.175). The median number of days between admission to a palliative care ward/mobile palliative care team and death did not differ significantly in sedated versus non-sedated patients (10 vs. 9 days; p = 0.491). CONCLUSION: This study provides insights into the practice of end-of-life sedation in Austria. Critical appraisal of these data will serve as a starting point for the development of nation-wide guidelines for palliative sedation in Austria.

The patient living with the deer: the special charm of home care visits in palliative care described in a case report.

BACKGROUND: Home care visits are crucial for individuals with palliative care (PC) needs, as they allow them to stay in the comfort of their own homes for as long as possible or to pass away surrounded by loved ones. These visits also provide PC teams with the opportunity to understand the patient as a whole person, replete with their own individual stories and needs. One aspect that can be particularly significant in a patient's life is their relationship with animals and pets. So far, there are no case reports on patients living with a deer at home. CASE DESCRIPTION: In this case, a patient with advanced non-Hodgkin's lymphoma was discharged from the emergency room to return home due to their desire to be with their loved ones. The hospital's PC team was consulted to ensure that the patient's needs were met at home. On the following day, the team was surprised to discover a special family member at the patient's residence: a deer. This deer was deeply affected by the patient's passing and was seen crying throughout the process. CONCLUSIONS: This case highlights the importance of supporting patients to die at home, not only for the patient and their loved ones but also for their beloved animals. In this case, if the patient had passed away in the hospital, the deer would not have had the opportunity to say goodbye and may have struggled to understand and process the loss.

Routine laboratory parameters to support decision on parenteral nutrition in palliative care.

Introduction: Parenteral nutrition (PN) is widely used in palliative care (PC), but there is limited evidence to support its use at the end of life (EOL). This aim of this was to investigate the relationship between routine laboratory parameters and survival in patients receiving PN, and to develop a decision tree model to support clinicians decide whether to start or forgo PN. Methods: The laboratory parameters of 113 patients with advanced diseases who were admitted to a specialized palliative care unit (PCU) were analyzed at two points in time: T0 = before PN, T1 = two weeks after initiation of PN. Univariate Mann-Whitney U-tests and multivariate linear regression models, as well as a decision tree analysis were computed; all in relation to survival time. Results: The final regression model was significant with p = 0.001 (adjusted R2 = 0.15) and included two predictors for survival time after PN initiation: the CRP/albumin ratio and urea at T1 (ps = 0.019). Decision tree analysis revealed three important predictors for classification of survival time after PN initiation: CRP, urea, and LDH (all at T0). Discussion: The decision tree model may help to identify patients likely to benefit from PN, thus supporting the clinical decision whether or not to start PN.

Aromatherapy in Palliative Care: A Single-Institute Retrospective Analysis Evaluating the Effect of Lemon Oil Pads against Nausea and Vomiting in Advanced Cancer Patients.

Aromatherapy is regularly used in the University Hospital Krems's palliative care unit. In a retrospective analysis, we investigated whether there were improvements in nausea and vomiting in patients with advanced cancers over a time span of 24 months. Data collection used the medical records of patients who were institutionally approved to receive routine aroma applications for alleviating nausea and vomiting. The efficacy of using lemon oil pads was tested with one-dimensional chi-squared tests. Sixty-six patients received 222 applications of lemon oil on cotton pads; no data were available for 17 applications. The adequate relief of nausea and vomiting was reported for 149 (73%) applications, whereas no symptom control was seen for 56 (27%) applications. For the 56 applications without symptom control, first- and second-line rescue medications were successful in 53 and 3 cases, respectively. The use of aromatherapy with lemon oil pads against nausea and vomiting was feasible for 73% of all applications. All patients who did not benefit from aromatherapy had effective symptom control with a rescue medication. Large randomized prospective trials are necessary to evaluate the benefit of the use of lemon oil pads against nausea and vomiting in patients with advanced cancer.

A Retrospective, Single-Center Analysis of Specialized Palliative Care Services for Patients with Advanced Small-Cell Lung Cancer.

Timely integration of specialized palliative care (SPC) has been shown to improve cancer patients' quality of life (QoL) and reduced the use of medical services. To evaluate the level of integration of SPC services for patients with advanced small-cell lung cancer (SCLC), we retrospectively analyzed medical records of patients from 2019 to 2021. Regarding the timing of referral to SPC services, we defined four cutoffs for early referral according to the current literature: (a) SPC provided ≤ 60 days after diagnosis; (b) SPC provided ≥ 60 days before death; (c) SPC provided ≥ 30 days before death; and (d) SPC provided ≥ 130 days before death. One hundred and forty-three patients (94.1%) were found to have locally advanced (stage III) or metastatic (stage IV) disease. Sixty-eight were not referred to SPC services (47.6%), whereas 75 patients received SPC (52.4%). We found a significantly higher number of referrals to SPC services for patients with higher ECOG (Eastern Cooperative Oncology Group) (i.e., ECOG ≥ 2) (p = 0.010) and patients with stage IV disease (p ≤ 0.001). The median overall survival (OS) for SCLC stage III/IV patients (n = 143) who did not receive SPC treatment was 17 months (95% CI 8.5-25.5), while those who did receive SPC treatment had a median OS of 8 months (95% CI 6.2-9.8) (p = 0.014). However, when we evaluated patients receiving SPC treatment in a timely manner before death as suggested by the different cutoffs indicated in the literature, they lived significantly longer when referred at a minimum of ≥60 or ≥130 days before death. Based on our findings, we suggest that patients with advanced SCLC should participate in a consultation with a SPC team in a timely manner to ensure a benefit of SPC for this patient group.

Evaluation of Antibody Responses to COVID-19 Vaccines among Solid Tumor and Hematologic Patients.

Vaccination is the primary public health strategy to cope with the COVID-19 pandemic. Although solid tumor and hematologic patients are at higher risk of serious COVID-19-related complications, data on immune responses to COVID-19 vaccines in this patient cohort are particularly scarce. The present study, therefore, aimed at the standardized determination of anti-SARS-CoV-2 spike protein antibody titers among non-vaccinated versus vaccinated solid tumor and hematologic patients who are under clinical observation or under treatment at the University Hospital Krems. Standardized anti-SARS-CoV-2 S antibody titers of a total of 441 patients were retrospectively analyzed. Our results show that antibody titers against the SARS-CoV-2 spike protein are significantly higher in solid tumor versus hematologic patients. While SARS-CoV-2 antibody titers were equal among sexes, an age-dependent decrease was observed. Of note, our studies additionally show that complete vaccination represents a valuable predictor for high anti-SARS-CoV-2 antibody responses in solid tumor and hematologic patients. In summary, to date, this is one of the largest studies to comprehensively evaluate the impact of various COVID-19 vaccines on anti-SARS-CoV-2 S antibody production in solid tumor and hematologic patients. Our findings aim to support future vaccination strategies in these highly vulnerable patients, including vaccination booster programs and alternative protective approaches.

Retrospective analysis of the prevalence of specialised palliative care services for patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) have a considerable symptom burden and may require extensive care for a long period of time. Palliative care (PC) has the potential to improve their quality of care and reduce their use of medical services. However, the role of specialised PC (SPC) in patients with MBC remains unclear. PATIENTS AND METHODS: We performed a retrospective analysis of the medical records of patients diagnosed with breast cancer (BC) from 2008 to 2018 at an university-based referral centre to examine the extent of early and late integration of SPC services for patients with MBC. A descriptive analysis of the patients was also established. RESULTS: In all, 932 patients were diagnosed with BC from 2008 to 2018; 225 of these patients had or developed metastases related to their BC. In addition, 132 patients received SPC (58.7%) and 93 patients did not receive SPC (41.3%). The median probability of overall survival (OS) for patients who did not receive SPC services was 3.6 years (95% CI 2.0 to 5.1) and 1.8 years (95% CI 1.3 to 2.3) (p<0.0001) for patients who did receive SPC. In multivariate analysis, referral to SPC services was independently associated with OS (HR 1.60, 95% CI 1.16 to 2.22, p=0.004). CONCLUSION: Patients who received SPC lived significantly shorter amounts of time than patients not referred for SPC services at our hospital. We concluded that the referral to SPC services was often too late and should be implemented earlier in the course of the disease. We suggest that patients with MBC should participate in a consultation by a SPC team ≤60 days after the start of systemic palliative anticancer therapy in addition to endocrine treatment. Larger prospective studies are needed to evaluate the benefit of the early integration of SPC services for patients with MBC.

Demystification of palliative care: what palliative care teams don't want you to think about them.

There is robust data that palliative care is prolonging life while there are still prejudices towards this discipline that have to be demystified. Patients, relatives and caregivers benefit from the concept of early integration of palliative care and therefore, palliative care should not be mainly regarded as end-of-life care.