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.

Leukocytoclastic Vasculitis Induced by Cocaine Adulterated with Levamisole.

Leukocytoclastic vasculitis is a cutaneous, small-vessel vasculitis. In 50% of cases the aetiology is idiopathic but it can be linked to drugs, infections, autoimmune disorders and various types of cancer. Levamisole is used as an adulterant in cocaine and heroin and has been associated with the development of leukocytoclastic vasculitis. We describe an atypical presentation of a patient with levamisole-induced leukocytoclastic vasculitis who presented with diffuse skin abscesses and a purpuric rash of the upper and lower limbs. LEARNING POINTS: In patients with intravenous drug consumption and a clinical presentation of leukocytoclastic vasculitis, it is important to consider levamisole as a possible contributing factor.Negative screening for MPO-ANCA and PR3-ANCA antibodies does not exclude levamisole-induced leukocytoclastic vasculitis.Diagnostic criteria for leukocytoclastic vasculitis induced by levamisole have not yet been established.

The role of palliative care in relapsed and metastatic head and neck cancer patients in a single ESMO integrated oncology and palliative care centre.

BACKGROUND: Palliative care (PC) for patients with advanced cancer improves symptom management and quality of life and may promote home deaths. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. The aim of this study was to describe the type of care and modalities of integration of specialized PC in a population of relapsed and/or metastatic head and neck cancer patients, followed in a single institution over 4 years. METHODS: Between January 2016 and December 2019, data on patients with relapsed and/or metastatic head and neck cancer not suitable for curative treatment diagnosed at the Oncology Institute of Southern Switzerland were reviewed retrospectively. Site, type and lines of treatment, treatment response, referral to specialist palliative care (yes or no), type of symptoms, tracheostomy and/or feeding-tube presence, and site of death were documented. Comparisons were made between patients benefitting from PC integration vs standard care. RESULTS: Eighty-six patients with relapsed/metastatic HNC were identified, 63 (73.3%) of whom were referred to specialized PC. Patients were mainly men (66, 76.7%), with a median age of 69 years (range 44-95). The most common site of tumour was the oropharynx (31, 36%), followed by the larynx (21, 24.4%), oral cavity (19, 22.1%), hypopharynx (14, 16.3%), and unknown primary (1, 1.2%). Forty-four patients (51.2%) were treated with systemic treatment. The median time interval between the diagnosis and palliative care referral was 1.7 months. At the time of our analysis, 69 patients had died (58 in the PC group and 11 in the non-PC group). Fifteen patients (25.9%) in the PC group and 4 (36.4%) in the non-PC group had received aggressive treatment (chemotherapy, tracheostomy and/or feeding tube) in the last month of life, with no significant difference between groups (p = 0.44). There was no difference in the incidence of home death (19.1% PC group vs 9.1% non-PC group, p = 0.67) or presence of caregiver (69.8% PC group vs 78.2% non-PC group, p = 0.58) between groups, while palliative care was associated with more opioid use (90.5% vs 17.4%, p < 0.0001). Patients in the PC group had a shorter survival compared to the non-PC group (5.7 vs 19.9 months, p = 0.0063). CONCLUSIONS: This study shows that patients appear to be at risk of receiving inappropriate invasive treatments close to death and of dying in hospital settings. Further research is needed to investigate how early PC may affect decision-making around treatments and improve HNC patients' holistic wellbeing.

Dexmedetomidine: a magic bullet on its way into palliative care-a narrative review and practice recommendations.

BACKGROUND AND OBJECTIVE: Dexmedetomidine is a potent adrenergic alpha-2 receptor agonist. It was first approved for sedation for mechanically ventilated patients. Being a sedative medication that is not associated with respiratory depression and holding analgesic properties fosters the interest for this drug in the palliative care field. The primary objectives of this review were to identify the key indications for the real-world use of dexmedetomidine in palliative care and other disciplines. METHODS: A narrative review after extensive PubMed search was performed from 1950 to present on October 21st 2021. The language of the publications was restricted to English, German, French and Italian. KEY CONTENT AND FINDINGS: (I) Current dexmedetomidine use. There is a growing body of evidence that dexmedetomidine may reduce the incidence and severity of delirium, reduce opioid-consumption and postoperative nausea in intensive care settings. It is also used to facilitate withdrawal from different substances (alcohol, opioids, heroin). Concerning safety aspects of the drug, some studies reported an increased rate of serious cardiovascular events in patients with pre-existing heart conditions due to bradycardia and arterial hypo- and hypertension. Since the drug has a main hepatic metabolism, dose reduction is mandatory in patients with hepatic impairment. (II) Dexmedetomidine and palliative care. There have been sporadic case reports about the successful use of dexmedetomidine in palliative care. Indications for symptom control included sedation for hyperactive delirium, cancer pain, opioid-induced-hyperalgesia, dystonia, cough, vomiting, shivering and dyspnea. It is mainly applied via the intravenous (i.v.), subcutaneous, but also nasal and, buccal routes. Admixture ("syringe-driver") studies showed that dexmedetomidine is compatible with morphine, hydromorphone, hyoscine and haloperidol. In 2021, a first prospective cohort study became available. Here, the authors reported promising result for dexmedetomidine use in hyperactive terminal delirium for reducing delirium intensity and agitation. Especially the unique "conscious sedation" or "awake sedation" that allows patients to arouse easily under sedation and report comfort or distress was discussed by the authors. CONCLUSIONS: In this review, we present the main findings for dexmedetomidine from palliative care settings and other disciplines. The potential benefits and criticalities of the drug are discussed and practical recommendations for its use are provided.

Hypercalcemia: An Underestimated Value Always Good for a Surprise.

We present the unusual case of a 62-year-old male with profound asthenia and dyspnea for the last two months. Blood exams showed a severe hypercalcemia. Suspecting an underlying malignancy, we performed a 18F-FDG PET-CT, revealing widespread metabolic uptakes in muscles, consistent with an inflammatory process. The muscular biopsy showed a non-necrotising granuloma with multinucleated giant cells, pathognomonic for the diagnosis of acute isolated muscular sarcoidosis. A high-dose steroid therapy was started with clinical improvement and serum calcium normalization.

Palliative Care For Patients with Advanced COPD in Primary Care.

Patients with advanced COPD have a high symptom burden that is often multidimensional. Identification of patients who might benefit from palliative care through validated identification tools, multidimensional symptom management, and timely discussion of advance planning are elements of a palliative care approach for these patients and their families. Coordination among stakeholders providing care and support to these patients is central to ensuring high-quality care and meeting all of their needs.

Association of Hashimoto's Thyroiditis and Burkitt Lymphoma: A Rare Condition to Be Considered.

We present the case of a 72-year-old woman who was diagnosed with Hashimoto's thyroiditis and who developed a low-grade fever, fatigue, and weight loss that prompted to perform a thyroid biopsy to rule out an underlying primary thyroid lymphoma. This case report offers the opportunity to review the association between Hashimoto's thyroiditis and primary thyroid lymphoma. Furthermore, it underlines the importance of considering the diagnosis of lymphoma when a thyroid mass is found in patients with an underlying Hashimoto's disease, as the timely management is essential for survival with this rare thyroid condition.

Palliative care integration for patients with advanced chronic obstructive pulmonary disease (COPD): Identifying essential components using participatory action research.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a life-limiting condition with palliative care needs. Despite increasing awareness about the role palliative care can play in care provision for patients with advanced COPD, integration in standard care remains underdeveloped. The unpredictability of the disease progression and misconceptions about palliative care being equivalent to end-of-life care often prevent a timely integrated approach in advanced COPD. AIM: To identify practices designed to increase integration of palliative care in the management of patients with advanced COPD in a respiratory service in Southern Switzerland. DESIGN: A participatory action research approach was chosen and key stakeholders were involved to develop new knowledge and practices, supported by a Theory of Change framework. Data from each cycle and retrospective analysis at the end of the whole research were analysed using thematic analysis. SETTING/PARTICIPANTS: Five action research cycles with seven healthcare professionals working in palliative or respiratory care settings were conducted. RESULTS: Three elements of integrated palliative care in advanced COPD were identified: multidimensional assessment, healthcare professionals' education and interdisciplinary team meetings, which are the pillars of a new integrated palliative care model for patients with advanced COPD. CONCLUSIONS: The new integrated palliative care model in advanced COPD includes essential elements with a focus on patients, healthcare professionals and care delivery. Further research on testing this model in clinical practice, service development, implementation processes and possible outcomes, including evaluation of the financial impact of integrated palliative care is necessary to foster this care approach across all possible settings.

Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection.

BACKGROUND: Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents. METHODS: We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-α levels were measured by ELISA. FINDINGS: Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-α serum levels. INTERPRETATION: In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity. FUNDING: Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.

Should end-of-life patients be enrolled as participants in clinical research? A best-fit framework synthesis.

AIM: To identify and appraise evidence about ethical concerns regarding conducting medical research with end-of-life patients. DESIGN: A best-fit framework synthesis of the literature regarding ethical issues in research involving adult patients at the end of life was conducted. DATA SOURCES: Five databases were searched (Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, MEDLINE, and PsychINFO) between January 2000-August 2019. REVIEW METHODS: Data were synthesized and categorized according to the moral positions described by Foster. RESULTS: In all, 18 papers that met the inclusion criteria were included in this review. These papers provided rich knowledge not only about various ethical objections to researching the end of life but also about the social, moral, and clinical requirements to perform rigorous studies on clinical interventions in this field. CONCLUSIONS: Research on people at end of life is not an unsolvable ethical dilemma between providing the best possible care and enhancing new therapies. It is important to find a balance between the moral duties of providing care and achieving research outcomes that are rigorous and meaningful for service users. IMPACT: Research ethics committees can be challenged by the evaluation of human research. This review provides up-to-date evidence on key challenges and ethical considerations about researching with end-of-life patients. SUMMARY STATEMENT: This study is a review of relevant evidence and key ethical challenges and issues around palliative and end-of-life research. Our findings provided important recommendations for clinicians, research, and ethics committee members when evaluating clinical research with people at their end of life.

Living with Advanced Chronic Obstructive Pulmonary Disease: A Qualitative Interview Study with Patients and Informal Carers.

The disease trajectory in chronic obstructive pulmonary disease (COPD) is characterised by a progressive decline in overall function, loss of independence and reduction of health-related quality of life. Although the symptom burden is high and care is often demanding, patients' and informal carers' experiences in living with advanced COPD are seldom described. This study sought to explore patients' and informal carers' experiences in living with advanced COPD and to understand their awareness about palliative care provision in advanced COPD. About 20 patients and 20 informal carers were recruited in a respiratory care service in Southern Switzerland. Semistructured individual interviews with participants were conducted on clinic premises and audio-recorded. Interviews lasted between 35 and 45 min. Data were analysed using thematic analysis. Living day to day with COPD, psychosocial dimension of the disease and management of complex care were the main themes identified. Patients and informal carers reported a range of psychological challenges, with feelings of guilt, discrimination and blame. Most of the participants had no knowledge of palliative care and healthcare services did not provide them with any information about palliative care approaches in advanced COPD. The reported psychological challenges may influence the relationship between patients, informal carers and healthcare professionals, adding further complexity to the management of this long-term condition. Further research is needed to explore new ways of managing complex care in advanced COPD and to define how palliative care may be included in this complex care network.

Conservative Management of COVID-19 Patients-Emergency Palliative Care in Action.

CONTEXT: The COVID-19 pandemic is spreading across the world. Many patients will not be suitable for mechanical ventilation owing to the underlying health conditions, and they will require a conservative approach including palliative care management for their important symptom burden. OBJECTIVES: To develop a management plan for patients who are not suitable for mechanical ventilation that is tailored to the stage their COVID-19 disease. METHODS: Patients were identified as being stable, unstable, or at the end of life using the early warning parameters for COVID-19. Furthermore, a COVID-19-specific assessment tool was developed locally, focusing on key symptoms observed in this population which assess dyspnoea, distress, and discomfort. This tool helped to guide the palliative care management as per patients' disease stage. RESULTS: A management plan for all patients' (stable, unstable, end of life) was created and implemented in acute hospitals. Medication guidelines were based on the limitations in resources and availability of drugs. Staff members who were unfamiliar with palliative care required simple, clear instructions to follow including medications for key symptoms such as dyspnoea, distress, fever, and discomfort. Nursing interventions and family involvement were adapted as per patients' disease stage and infection control requirements. CONCLUSION: Palliative care during the COVID-19 pandemic needs to adapt to an emergency style of palliative care as patients can deteriorate rapidly and require quick decisions and clear treatment plans. These need to be easily followed up by generalist staff members caring for these patients. Furthermore, palliative care should be at the forefront to help make the best decisions, give care to families, and offer spiritual support.

Pancreatic Pseudocysts in the Mediastinal Space: An Urban Legend?

Pancreatic pseudocysts are a frequent complication of chronic pancreatitis. Nonetheless, they seldom extend beyond the peripancreatic region. However, migration towards the mediastinum may cause heterogeneous and non-specific symptoms, such as dysphagia, chest pain and dyspnoea, which depend on the localization and extension of the cysts. We present the case of a patient with chronic pancreatitis who was admitted to our ward for low-grade fever and mild dyspnoea and who rapidly developed bilateral laterocervical swelling associated with acute dyspnoea and trismus. A total body CT scan showed multiple abdominal pancreatic pseudocysts, one of which had migrated to the mediastinum and towards the retropharyngeal space. Clinicians should always consider the possibility of extra-pancreatic pseudocysts in patients with known pancreatitis so that uncommon clinical presentations with a potentially fatal outcome will be recognized. LEARNING POINTS: Mediastinal pancreatic pseudocysts are a rare manifestation of acute and chronic pancreatitis.The clinical presentation of mediastinal pancreatic pseudocysts is variable, and they may rarely have a fatal outcome.

Palliative Care Provision for Patients with Advanced Chronic Obstructive Pulmonary Disease: A Systematic Integrative Literature Review.

Although chronic obstructive pulmonary disease (COPD) is recognized as being a life-limiting condition with palliative care needs, palliative care provision is seldom implemented. The disease unpredictability, the misconceptions about palliative care being only for people with cancer, and only relevant in the last days of life, prevent a timely integrated care plan. This systematic review aimed to explore how palliative care is provided in advanced COPD and to identify elements defining integrated palliative care. Eight databases, including MEDLINE, EMBASE and CINAHL, were searched using a comprehensive search strategy to identify studies on palliative care provision in advanced COPD, published from January 1, 1960 to November 30, 2017. Citation tracking and evaluation of trial registers were also performed. Study quality was assessed with a critical appraisal tool for both qualitative and quantitative data. Of the 458 titles, 24 were eligible for inclusion. Experiences about advanced COPD, palliative care timing, service delivery and palliative care integration emerged as main themes, defining a developing taxonomy for palliative care provision in advanced COPD. This taxonomy involves different levels of care provision and integrated care is the last step of this dynamic process. Furthermore, palliative care involvement, holistic needs' assessment and management and advance care planning have been identified as elements of integrated care. This literature review identified elements that could be used to develop a taxonomy of palliative care delivery in advanced COPD. Further research is needed to improve our understanding on palliative care provision in advanced COPD.

Intractable Neck Pain in an Oncologic Palliative Care Setting: Is Cancer Always the Answer?

Refractory pain is a common manifestation in an oncologic palliative care setting and represents a major challenge for health care professionals involved in care provision. The underlying neoplasm and its dissemination are the foremost pathophysiologic mechanism for the development of pain in patients with advanced cancer. Nonetheless, other etiologies such as trauma and infections need to be considered by clinicians in this particular care setting. The authors present the case of a patient with a recent diagnosis of hepatocellular carcinoma, suffering from intractable neck pain, progressive worsening of her general conditions, and the onset of a generalized seizure. The clinical suspicion of a bacteremia with central nervous system involvement was confirmed by the performed work-up, and a Listeria monocytogenes meningoencephalitis was diagnosed. The purpose of this case report is to raise clinicians' awareness on infectious complications, which may increase the symptom burden in patients treated in an oncologic palliative care setting. Moreover, the manifestation of such complications may be misinterpreted as the consequence of the underlying neoplasm, further delaying the diagnostic and therapeutic management in this particular population.

Spontaneous Osteonecrosis of the Jaw During Bisphosphonate Therapy: An Unusual Etiology of the Numb Chin Syndrome.

The numb chin syndrome is a rare manifestation of intractable pain in the palliative care setting and represents a major therapeutic challenge. The reported etiologies of the numb chin syndrome include trauma, infections, immune-mediated systemic conditions, and malignancy, both through local infiltration or compression of the inferior alveolar nerve sheath. The authors present the case of a patient with long-standing multiple myeloma, suffering from numb chin syndrome caused by a spontaneous osteonecrosis of the jaw after bisphosphonate therapy. Intractable unilateral orofacial pain over the right chin and lower lip with associated numbness and paresthesia in the distribution area of the mental nerve were the clinical features. A complex pharmacological therapy, including methadone, carbamazepine, and dexamethasone was started, with insufficient pain control. In consideration of the prevalent neuropathic etiology, the authors opted for a locoregional nerve block of the mandibular nerve with bupivacaine and clonidine. The interdisciplinary approach was successful, and the patient was discharged with satisfactory pain control. The purpose of this report is to demonstrate the complexity of the therapeutic approach, which may include pharmacological measures and interventional procedures to improve symptom management in this challenging clinical condition.

Multidrug infusions in a Swiss palliative care unit: assessment of frequent combinations in terms of clinical effectiveness, compatibility, and stability.

PURPOSE: The objectives of this study were to trace, monitor, and assess for clinical effectiveness, visual compatibility, and stability of commonly used combinations of drugs for patients hospitalized in a Swiss palliative care unit, over a 12-month period. METHODS: In this longitudinal analysis, commonly used multidrug combinations were monitored with a duly created data collection sheet for healthcare professionals. Assessment of visual changes of the mixtures and the evaluation of major changes in the overall symptom control over time were recorded. The clinical changes were classified according to reasonable correlation to the modality of drug administration and not to clinical evolution of the underlying disease. RESULTS: Over a 12-month period, a total of 48 multidrug infusions were recorded and monitored. The infusions were composed of two, three, four, or five active principles. Infusions were given over a 24-h period, mainly intravenously, either through an implantable venous access port or a peripheral venous access. Main diluent was normal saline solution. Commonly used drug combinations included morphine and haloperidol, morphine, haloperidol and octreotide, morphine, haloperidol, octreotide, and chlorpromazine. No precipitations were observed during the study. Patients maintained a clinical stability and no salient changes in symptom control were attributed to inefficacy of the multidrug infusions. CONCLUSIONS: The use of multidrug infusions for parenteral administration appears to confirm an adequate visual compatibility and stability, while maintaining effectiveness in terms of overall symptom control.