Parenteral Hydration in Dying Patients With Cancer: A National Registry Study.

CONTEXT: Clinically assisted hydration during end-of-life care among patients with cancer is controversial; practice varies between clinical settings and countries, and there is a lack of evidence. OBJECTIVES: To examine whether breathlessness, respiratory secretion, or confusion correlates with receiving parenteral hydration during end of life, adjusted for sex, age, and place of death. METHODS: The Swedish Register of Palliative Care database was used to collect data about the usage of parenteral hydration during the last day of life, and the occurrence of three symptoms during the last week. Adults dying from cancer during 2011-2021 in hospitals, in residential care homes, and within specialized palliative care were included. Correlation between parenteral hydration and symptoms was examined using χ2-test and logistic regression. RESULTS: A total of 147,488 patients were included in the study. Parenteral hydration was more often prescribed to younger persons, to men, and in acute hospitals (compared to other settings), p < 0.001 in all three comparisons. Patients with hematological malignancies (20%) and ovarian cancer (16%) were most likely to receive parenteral hydration, while those with brain tumors (6%) were least likely. The presence of all three analyzed symptoms during the last week (breathlessness, respiratory secretion, and confusion) were significantly correlated with having received parenteral hydration during the last day of life (p < 0.001). In the final logistic regression model adjusted for age, sex, and place of death, the only symptom with remaining correlation to parenteral hydration was breathlessness (OR 1.56, 95% CI 1.50-1.6). CONCLUSION: There is an association between parenteral hydration and increased breathlessness in patients with cancer. Provision of parenteral hydration is more prevalent in men, younger patients, and those with hematological malignancies or ovarian cancer, and most widespread in acute hospital settings.

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. The optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis, and elevated biomarkers of NET formation are associated with poor prognosis. OBJECTIVES: To investigate the association between NET formation and occult cancer in patients with VTE. METHODS: Blood biomarkers associated with NETs and neutrophil activation (nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) were quantified in patients with VTE. The primary outcome was cancer diagnosed during a one-year follow-up. RESULTS: This study included 460 patients with VTE, of which 221 (48%) had isolated deep vein thrombosis. Forty-three patients had active cancer at inclusion and were excluded from the primary analysis Cancer during follow-up was diagnosed in 29 of 417 (7.0%) patients. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/mL increase of H3Cit-DNA was 1.79 (95% CI, 1.03-3.10). Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA than cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, previous cancer, and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/mL increase of H3Cit-DNA [95% CI, 1.35-3.13]). CONCLUSIONS: H3Cit-DNA is an independent predictor for occult cancer in patients with VTE and elevated in cancer-associated VTE, suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE and that elevated NET formation is a hallmark of cancer-associated VTE.

Symptom Management and Support in Dying Patients with Cancer and Coronavirus Disease-19-A Register-Based Study.

OBJECTIVE: Little is known to what extent access to specialist palliative care (SPC) for cancer patients dying with coronavirus disease-2019 (COVID-19) affects the occurrence of breakthrough symptoms, symptom relief, and overall care, compared to hospital deaths. Our aim was to include patients with both COVID-19 and cancer and compare those dying in hospitals with those dying in SPC with reference to the quality of end-of-life care. METHODS: Patients with both cancer and COVID-19 who died in hospitals (n = 430) and within SPC (n = 384) were identified from the Swedish Register of Palliative Care. The hospital and SPC groups were compared regarding the quality of end-of-life care, including the occurrence of 6 breakthrough symptoms during the last week in life, symptom relief, end-of-life care decisions, information, support, and human presence at death. RESULTS: Breakthrough of breathlessness was more common in the hospital patients compared to the SPC patients (61% and 39%, respectively; p < .001), while pain was less common (65% and 78%, respectively; p < .001). Breakthrough of nausea, anxiety, respiratory secretions, or confusion did not differ. All 6 symptoms, except for confusion, were more often completely relieved in SPC (p = .014 to p < .001 in different comparisons). In SPC, a documented decision about the goal being end-of-life care and information about this were more common than in hospitals (p < .001). Also, to have family members present at the time of death and for family members to be offered a follow-up talk afterward was more common in SPC (p < .001). CONCLUSION: More systematic palliative care routines may be an important factor for better symptom control and higher quality of end-of-life care in hospitals.

Symptoms, symptom relief and support in COVID-19 patients dying in hospitals during the first pandemic wave.

BACKGROUND: At the time of the first wave of the COVID-19 pandemic in Sweden, little was known about how effective our regular end-of-life care strategies would be for patients dying from COVID-19 in hospitals. The aim of the study was to describe and evaluate end-of-life care for patients dying from COVID-19 in hospitals in Sweden up until up until 12 November 2020. METHODS: Data were collected from the Swedish Register of Palliative Care. Hospital deaths during 2020 for patients with COVID-19 were included and compared to a reference cohort of hospital patients who died during 2019. Logistic regression was used to compare the groups and to control for impact of sex, age and a diagnosis of dementia. RESULTS: The COVID-19 group (1476 individuals) had a lower proportion of women and was older compared to the reference cohort (13,158 individuals), 81.8 versus 80.6 years (p < .001). Breathlessness was more commonly reported in the COVID-19 group compared to the reference cohort (72% vs 43%, p < .001). Furthermore, anxiety and delirium were more commonly and respiratory secretions, nausea and pain were less commonly reported during the last week in life in the COVID-19 group (p < .001 for all five symptoms). When present, complete relief of anxiety (p = .021), pain (p = .025) and respiratory secretions (p = .037) was more often achieved in the COVID-19 group. In the COVID-19 group, 57% had someone present at the time of death compared to 77% in the reference cohort (p < .001). CONCLUSIONS: The standard medical strategies for symptom relief and end-of-life care in hospitals seemed to be acceptable. Symptoms in COVID-19 deaths in hospitals were relieved as much as or even to a higher degree than in hospitals in 2019. Importantly, though, as a result of closing the hospitals to relatives and visitors, patients dying from COVID-19 more frequently died alone, and healthcare providers were not able to substitute for absent relatives.

Dying from COVID-19 in nursing homes-sex differences in symptom occurrence.

BACKGROUND: Coronavirus disease 2019 (COVID-19), is a disease with diverse presentation. Several studies have shown different occurrence of symptoms for women and men, but no studies have been found examining sex differences in clinical presentation for nursing home residents dying from COVID-19. The objective of this study was to describe sex and age differences and the impact of a dementia diagnosis on symptom occurrence during the last week in life for persons dying from COVID-19 in nursing homes. METHODS: This is a population-based retrospective study based on data from the Swedish Register of Palliative Care. A total of 1994 residents aged 65 or older who died from COVID-19 in nursing homes were identified. The impact of sex, age and a dementia diagnosis on six different symptoms was analysed using chi2-test and multivariate logistic regression. RESULTS: Residents dying from COVID-19 were more often men (p < .002). Men more often had dyspnoea and death rattles (p < .001). Nausea was more common in women (p < .001). No sex differences in the occurrence of pain, anxiety or confusion were seen. Dyspnoea and nausea were less commonly reported in residents with dementia (p < .001). CONCLUSIONS: We found sex differences in symptom presentation for fatal COVID-19 in nursing home settings which remained after adjusting for age. Residents with a dementia diagnosis had fewer symptoms reported before death compared to those without dementia. Clinical presentation of fatal COVID-19 differs between women and men in nursing homes. Residents with fatal COVID-19 present with more unspecific and less prominent symptoms when also suffering from dementia.

COVID-19: Symptoms in Dying Residents of Nursing Homes and in Those Admitted to Hospitals.

Objective: To compare symptom prevalence and relief in residents who died in nursing homes with residents who were acutely referred to hospitals. Design: Data on symptoms during the last week of life from the Swedish Register of Palliative Care (SRPC). Setting and Subjects: Nursing homes (n = 1903 deaths) and hospitals in Sweden (n = 202 nursing home residents who were admitted to hospital before death). Data were retrieved on August 24, 2020. Results: Residents who died in hospitals had more breakthrough symptoms of breathlessness (60% vs. 31%, p < 0.0001) and delirium (41% vs. 25%, p < 0.0001) than those who died in nursing homes. When symptoms were present, complete symptom relief was seen less often in hospitals compared with nursing homes (breathlessness, 28% vs. 47%, p < 0.001; delirium, 10% vs. 35%, p < 0.0001; respiratory secretions, 30% vs. 55%, p < 0.0001). Conclusion: Despite access to oxygen and pharmacologic/nonpharmacologic therapies in hospitals, symptom relief in dying nursing home residents acutely admitted to hospitals was lower compared with those who died in nursing homes, possibly because of differences in patient characteristics.

Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer.

Predicting survival accurately in patients with advanced cancer is important in guiding interventions and planning future care. Objective tools are therefore needed. Blood biomarkers are appealing due to their rapid measurement and objective nature. Thrombosis is a common complication in cancer. Recent data indicate that tumor-induced neutrophil extracellular traps (NETs) are pro-thrombotic. We therefore performed a comprehensive investigation of circulating markers of neutrophil activation, NET formation, coagulation and fibrinolysis in 106 patients with terminal cancer. We found that neutrophil activation and NET markers were prognostic in terminal cancer patients. Interestingly, markers of coagulation and fibrinolysis did not have a prognostic value in this patient group, and there were weak or no correlations between these markers and markers of neutrophil activation and NETs. This suggest that NETs are linked to a poor prognosis through pathways independent of coagulation. Additional studies are needed to determine the utility of circulating neutrophil activation and NET markers, alone or in concert with established clinical parameters, as objective and reliable prognostic tools in advanced cancer.

Patient interactive digital support for women with adjuvant endocrine therapy in order to increase compliance and quality of life.

PURPOSE: The primary aim of the study was to develop and investigate a patient interactive digital support (an app) for patients on adjuvant endocrine breast cancer treatment. Patient's interactive digital applications are a fast-growing area for research and development. In general, patients want more information and support with regard to their diagnosis, treatment and self-care. At the same time, the health care system has limited resources for follow-up. Our primary endpoints were usability of the app and if it added any value to the patients. METHODS: We designed and constructed a prototype, in dialogue with patients, containing four main modules for registration of drug compliance, performed physical exercise, self-care activities, and questions on health and quality of life. The app was then tested by patients and improved further before we completed a pilot study in which 15 patients used the app for 3 months. RESULTS: Patients perceived the app easy to use with a very high median system usability score of 88.8, range 30-100. The 15 women registered in total 4251 times, range 118 to 372. The majority of registrations concerned compliance (adherence to treatment) and physical exercise. CONCLUSION: The app was perceived easy to use and of support in every-day life of breast cancer survivors. How to best integrate electronically collected patient reported outcome measures in clinical routine needs to be further studied, and future research will show if it will be cost-effective in terms of better health outcome and less resource use.

Were Clinical Routines for Good End-of-Life Care Maintained in Hospitals and Nursing Homes During the First Three Months of the Outbreak of COVID-19? A National Register Study.

CONTEXT: Although the coronavirus disease 2019 (COVID-19) pandemic might affect important clinical routines, few studies have focused on the maintenance of good quality in end-of-life care. OBJECTIVES: The objective was to examine whether adherence to clinical routines for good end-of-life care differed for deaths because of COVID-19 compared with a reference cohort from 2019 and whether they differed between nursing homes and hospitals. METHODS: Data about five items reflecting clinical routines for persons who died an expected death from COVID-19 during the first three months of the pandemic (March-May 2020) were collected from the Swedish Register of Palliative Care. The items were compared between the COVID-19 group and the reference cohort and between the nursing home and hospital COVID-19 deaths. RESULTS: About 1316 expected deaths were identified in nursing homes and 685 in hospitals. Four of the five items differed for total COVID-19 group compared with the reference cohort: fewer were examined by a physician during the last days before death, pain and oral health were less likely to be assessed, and fewer had a specialized palliative care team consultation (P < 0.0001, respectively). Assessment of symptoms other than pain did not differ significantly. The five items differed between the nursing homes and hospitals in the COVID-19 group, most notably regarding the proportion of persons examined by a physician during the last days (nursing homes: 18%; hospitals: 100%). CONCLUSION: This national register study shows that several clinical routines for end-of-life care did not meet the usual standards during the first three months of the COVID-19 pandemic in Sweden. Higher preparedness for and monitoring of end-of-life care quality should be integrated into future pandemic plans.

Symptom Relief Is Possible in Elderly Dying COVID-19 Patients: A National Register Study.

Background: Increasing numbers of people dying from COVID-19 are reported, but data are lacking on the way they die. Objective: To study symptoms and symptom relief during the last week of life, comparing nursing homes with hospitals. Design: The Swedish Register of Palliative Care with national coverage was used. Breakthrough symptoms were registered as Yes/No. Symptom relief was recorded on a 3-grade scale as complete-partial-no relief. All deaths in COVID-19 were contrasted to deaths in a reference population (deaths 2019). Deaths at nursing homes were compared with deaths in hospitals. Setting and Subjects: All deaths in hospitals or nursing homes (n = 490) were analyzed. Deaths in other settings (specialized palliative care wards [n = 11], in palliative home care [n = 2], or in their own homes [n = 8]) were excluded (n = 21). Only patients with expected deaths (n = 390) were entered in the final analysis. Results: Breathlessness as a breakthrough symptom was more common in COVID-19 patients than in the 2019 reference population (p < 0.001) and relief of breathlessness, as well as anxiety, delirium, and death rattles was less successful in COVID-19 patients (p < 0.05 to p < 0.01 in different comparisons). Patients were older in nursing homes than in hospitals (86.6 years vs. 80.9 years, p < 0.001) and more often female (48% vs. 34%, p < 0.001). Breakthrough of breathlessness was much more frequently reported in hospital settings than in nursing homes, 73% versus 35% (p < 0.0001), and complete relief was more rarely possible in hospitals, 20% versus 42% (p < 0.01). The proportion of partial relief+complete relief was comparable, 92% versus 95% (ns). Also, anxiety and pain were more often completely relieved in nursing homes (p < 0.01 in both comparisons). Conclusion: The lower symptom prevalence in nursing homes may be explained by elderly frail residents dying already in the first phase of the COVID-19 disease, before acute respiratory distress syndrome develops.

Continuous subcutaneous infusion for pain control in dying patients: experiences from a tertiary palliative care center.

BACKGROUND: Continuous subcutaneous infusion (CSCI) via ambulatory infusion pump (AIP) is a valuable method of pain control in palliative care. When using CSCI, low-dose methadone as add-on to other opioids might be an option in complex pain situations. This study aimed to investigate the effects, and adverse effects, of CSCI for pain control in dying patients, with particular interest in methadone use. METHODS: This was an observational cohort study. Imminently dying patients with pain, admitted to specialized palliative inpatient wards and introduced on CSCI, were monitored daily by staff for symptoms (Integrated Palliative Care Outcome Scale - IPOS), sedation (Richmond Agitation and Sedation Scale - RASS), performance status (Eastern Cooperative Oncology Group - ECOG) and delirium (Confusion Assessment Method - CAM). RESULTS: Ninety-three patients with a median survival of 4 days were included. Of the 47 patients who survived ≥3 days, the proportion of patients with severe/overwhelming pain decreased from 45 to 19% (p < 0.001) after starting CSCI, with only a moderate increase in morphine equivalent daily dose of opioids (MEDD). Alertness was marginally decreased (1 point on the 10-point RASS scale, p = 0.001), whereas performance status and prevalence of delirium, regardless of age, remained unchanged. Both patients with methadone as add-on (MET, n = 13) and patients with only other opioids (NMET, n = 34), improved in pain control (p < 0.05 and 0.001, respectively), despite that MET patients had higher pain scores at baseline (p < 0.05) and were on a higher MEDD (240 mg vs.133 mg). No serious adverse effects demanding treatment stop were reported. CONCLUSIONS: CSCI via AIP is an effective way to reduce pain in dying patients without increased adverse effects. Add-on methadone may be beneficial in patients with severe complex pain.

Better quality of end-of-life care for persons with advanced dementia in nursing homes compared to hospitals: a Swedish national register study.

BACKGROUND: Hospitalisation of patients with advanced dementia is generally regarded as less preferable compared to care at home or in a nursing home. For patients with other diagnoses, young age has been associated with better end-of-life care. However, studies comparing the quality of palliative care for persons with advanced dementia in hospitals and nursing homes are scarce. The aim of this study was to investigate whether quality of end-of-life care for patients with dementia depends on age, gender and place of death. METHODS: The Swedish Register of Palliative Care (SRPC) was used to identify patients who died from dementia in hospitals or nursing homes during a three-year period. The likelihood of death occurring at a hospital, based on age and gender differences, was calculated. Associations between 13 end-of-life care quality indicators collected from the SRPC and age, gender and place of care were examined in a logistic regression model. RESULTS: Death at a hospital was associated with poorer quality of end-of-life care for 10 of the 13 measured outcomes when compared to death at a nursing home, and with better quality according to two of the outcomes. Death at a hospital was more common for men compared to women and for younger patients compared to older. Receiving fluids intravenously or via enteral tube in the last 24 h of life was strongly associated with death at a hospital. Women were more likely to have their oral health assessed and less likely to have pressure ulcers at death. Eight of 12 end-of-life care outcomes showed better results for the age group 65 to 84 years compared to those 85 years or older. CONCLUSIONS: Death in hospitals was associated with poorer quality of end-of-life care compared to death in nursing homes. Our data support the importance of advance care planning and individual assessments in nursing homes to avoid referral to hospitals during end of life. Despite established recommendations to avoid hospitalisation if possible, there were strong associations between younger age, male gender and hospitalisation in the end of life. Further studies are needed to investigate the role of socioeconomic factors in end-of-life care for this patient group.

Dying From COVID-19: Loneliness, End-of-Life Discussions, and Support for Patients and Their Families in Nursing Homes and Hospitals. A National Register Study.

CONTEXT: Preparation for an impending death through end-of-life (EOL) discussions and human presence when a person is dying is important for both patients and families. OBJECTIVES: The aim was to study whether EOL discussions were offered and to what degree patients were alone at time of death when dying from coronavirus disease 2019 (COVID-19), comparing deaths in nursing homes and hospitals. METHODS: The national Swedish Register of Palliative Care was used. All expected deaths from COVID-19 in nursing homes and hospitals were compared with, and contrasted to, deaths in a reference population (deaths in 2019). RESULTS: A total of 1346 expected COVID-19 deaths in nursing homes (n = 908) and hospitals (n = 438) were analyzed. Those who died were of a more advanced age in nursing homes (mean 86.4 years) and of a lower age in hospitals (mean 80.7 years) (P < 0.0001). Fewer EOL discussions with patients were held compared with deaths in 2019 (74% vs. 79%, P < 0.001), and dying with someone present was much more uncommon (59% vs. 83%, P < 0.0001). In comparisons between nursing homes and hospital deaths, more patients dying in nursing homes were women (56% vs. 37%, P < 0.0001), and significantly fewer had a retained ability to express their will during the last week of life (54% vs. 89%, P < 0.0001). Relatives were present at time of death in only 13% and 24% of the cases in nursing homes and hospitals, respectively (P < 0.001). The corresponding figures for staff were 52% and 38% (P < 0.0001). CONCLUSION: Dying from COVID-19 negatively affects the possibility of holding an EOL discussion and the chances of dying with someone present. This has considerable social and existential consequences for both patients and families.

Quantification of citrullinated histones: Development of an improved assay to reliably quantify nucleosomal H3Cit in human plasma.

BACKGROUND: Recent data propose a diagnostic and prognostic capacity for citrullinated histone H3 (H3Cit), a marker of neutrophil extracellular traps (NETs), in pathologic conditions such as cancer and thrombosis. However, current research is hampered by lack of standardized assays. OBJECTIVES: We aimed to develop an assay to reliably quantify nucleosomal H3Cit in human plasma. METHODS: We assessed the common practice of in vitro enzymatically modified histone H3 as calibration standards and the specificity of available intrapeptidyl citrulline antibodies. Based on our findings, we developed and validated a novel assay to quantify nucleosomal H3Cit in human plasma. RESULTS: We show that enzymatically citrullinated H3 proteins are compromised by high enzyme-dependent lot variability as well as instability in plasma. We furthermore demonstrate that the majority of commercially available antibodies against intrapeptidyl citrulline display poor specificity for their reported target when tested against a panel of semi-synthetic nucleosomes containing distinct histone H3 citrullinations. Finally, we present a novel assay utilizing highly specific monoclonal antibodies and semi-synthetic nucleosomes containing citrulline in place of arginine at histone H3, arginine residues 2, 8, and 17 (H3R2,8,17Cit) as calibration standards. Rigorous validation of this assay shows its capacity to accurately and reliably quantify nucleosomal H3Cit levels in human plasma with clear elevations in cancer patients compared to healthy individuals. CONCLUSIONS: Our novel approach using defined nucleosome controls enables reliable quantification of H3Cit in human plasma. This assay will be broadly applicable to study the role of histone citrullination in disease and its utility as a biomarker.

Methadone in Swedish specialized palliative care-Is it the magic bullet in complex cancer-related pain?

CONTEXT: Despite being associated with dependence and social stigma, methadone is a potential end-of-life option in complex cancer pain. OBJECTIVES: To explore attitudes and opinions about methadone and its potential role and current use in complex end-of-life pain. METHODS: Semi-structured interviews (n = 30) with physicians in specialized palliative care, transcribed and analyzed with conventional qualitative content analysis. RESULTS: According to the physicians, patients and relatives expressed unexpectedly few negative attitudes, not affecting methadone's use as an analgesic. Complex pain in bone-metastatic cancer of the prostate, breast and kidney, as well as pancreatic cancer and sarcomas were recurrent suggestions of appropriate indications. Most of the informants stated that they applied a mechanism-based treatment and mainly prescribed low-dose methadone as an add-on to an existing opioid therapy to benefit from methadone´s proposed NMDA-receptor inhibiting properties, e.g. in cases with reduced opioid sensitivity. Despite its complex pharmacokinetics with a long half-life, most informants expressed defined strategies to avoid side-effects such as respiratory depression, especially when initiating treatment in the home-care setting. While many palliative care physicians expressed an overly enthusiastic attitude, others stressed the risks of overconfidence, low precision in use, and overlooked treatment options. Besides the obvious physical pain-relieving effects, they stated that effective pain relief could result in a reduced workload and emotional empowerment, both for physicians and staff. CONCLUSION: Methadone, especially in the form of low-dose add-on to other opioids is widely advocated in Swedish specialized palliative care as a practical and safe method with rapid onset in complex pain situations at the end of life.

The Use of Low-Dose Methadone as Add-On to Regular Opioid Therapy in Cancer-Related Pain at End of Life: A National Swedish Survey in Specialized Palliative Care.

Background: Low-dose methadone in addition to another ongoing opioid therapy is a promising approach for managing complex cancer-related pain and is, despite limited evidence, used in clinical practice. Objective: To investigate the use of low-dose methadone in specialized palliative care in Sweden. Design: Specialized palliative care services in Sweden answered a survey regarding methadone use in individual patients over 12 months. Setting/Subjects: The survey was an add-on to the Swedish Register of Palliative Care's (SRPC) mandatory end-of-life questionnaire (ELQ). Results: Sixty of 133 invited units (45%) participated in the study. A total of 4780 ELQs were registered. Four hundred ten of these patients received methadone (9%). In 96% of these patients, methadone was prescribed as an add-on to ongoing opioid therapy, mostly because of poor pain control due to mixed nociceptive and neuropathic pain (70%). Methadone was used for a median of 21 days, in 86% of cases until death. Mean daily methadone doses increased from 7 mg at start to 21 mg (p < 0.005) during the last 24 hours. Corresponding morphine equivalent daily doses of other opioids were 184 and 199 mg (p < 0.05), respectively. A pain-relieving effect was reported in 94% of the patients. Adverse effects were seen in 20% of the patients; none of these was severe. Conclusion: The addition of low-dose methadone to an ongoing opioid therapy in patients with complex cancer-related pain is well established in Swedish specialized palliative care. It appears to have good pain-relieving effects and to be safe.

Neutrophil Extracellular Traps: Villains and Targets in Arterial, Venous, and Cancer-Associated Thrombosis

Recent studies have demonstrated a role of neutrophils in both venous and arterial thrombosis. A key prothrombotic feature of neutrophils is their ability to release web-like structures composed of DNA filaments coated with histones and granule proteins referred to as neutrophil extracellular traps (NETs). NETs were discovered over a decade ago as part of our first line of host defense against invading microorganisms. Although NETs have a protective role against pathogens, recent data suggest that an uncontrolled and excessive NET formation within the vasculature may contribute to pathological thrombotic disorders. In vitro studies suggest that NETs promote vessel occlusion by providing a scaffold for platelets, red blood cells, extracellular vesicles, and procoagulant molecules, such as von Willebrand factor and tissue factor. In addition, NET components enhance coagulation by both activating the intrinsic pathway and degrading an inhibitor of the extrinsic pathway (tissue factor pathway inhibitor). NET formation has, therefore, been proposed to contribute to thrombus formation and propagation in arterial, venous, and cancer-associated thrombosis. This review will describe animal and human studies suggesting a role of NETs in the pathogenesis of various thrombotic disorders. Targeting NETs may be a novel approach to reduce thrombosis without affecting hemostasis.

[The neutrophil's multifaceted traps - the Dr Jekyll and Mr Hyde of the immune system]. / Neutrofilernas märkliga fångstnät - Immunförsvarets Dr Jekyll och Mr Hyde.

Neutrophil extracellular traps (NETs) were first described over a decade ago as part of our innate immune system. Through the extracellular release of web-like structures composed of DNA and histones coated with antimicrobial peptides, the neutrophil was shown to entrap and disarm invading microorganisms. Recent data now propose a central role of NETs in a variety of non-infectious conditions - such as autoimmunity, thrombosis, and cancer - revealing that NETs may not only be beneficial, but also harmful if uncontrolled. Continued investigations into the clinical relevance of NETs will shed further light on the utility of biomarkers associated with NETs, and may open for new therapeutic options in several disease settings.

A clinical practice-based evaluation of the RIETE score in predicting occult cancer in patients with venous thromboembolism.

The association between venous thromboembolism (VTE) and occult cancer is well established. However, the benefit of cancer screening in all VTE patients remains controversial. The Registro Informatizado Enfermedad TromboEmbólica (RIETE) score is a recently proposed risk score to identify VTE patients at high risk of occult cancer. We evaluated the performance of the RIETE score in a routine clinical setting comprising patients presenting with VTE between January 1 and December 31, 2014, at Danderyd University hospital. Out of 488 VTE patients, 47 (9.6%) patients received a new cancer diagnosis during a 24-month follow-up. After exclusion of patients with cancer diagnosed at baseline (≤ 10 days after VTE, n = 16), 472 patients were considered eligible for cancer screening. Among these 472 patients, 31 (6.6%) received a cancer diagnosis during follow-up. The cumulative incidence was high after both unprovoked (8.5%) and provoked (4.8%) VTE. The RIETE score was evaluated in 467 of these patients. Interestingly, a high RIETE score was not significantly associated with cancer diagnosis during follow-up (OR 1.78; 95% CI 0.85-3.63), which was mainly due to a poor performance in women (OR 1.04; 95% CI 0.30-2.83). In summary, we observed a relatively high incidence of occult cancer in both unprovoked and provoked VTE. The RIETE score performed poorly in identifying patients at high risk of occult cancer in our VTE population. Additional risk assessment models are warranted to identify VTE patients who would benefit from extensive cancer screening.

Cancer patients hospitalised in the last week of life risk insufficient care quality - a population-based study from the Swedish Register of Palliative Care.

BACKGROUND: One-quarter of all cancer deaths in Sweden occur in hospitals. If the place of death affects the quality of end-of-life (EOL) is largely unknown. METHODS: This population-based, retrospective study included all adults cancer deaths reported to the Swedish Register of Palliative Care in 2011-2013 (N = 41,729). Hospital deaths were compared to deaths occurring in general or specialised palliative care, or in nursing homes with respect to care quality indicators in the last week of life. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with specialised palliative home care as reference. RESULTS: Preferred place of death was unknown for 63% of hospitalised patients and consistent with the actual place of death in 25% compared to 97% in palliative home care. Hospitalised patients were less likely to be informed when death was imminent (OR: 0.3; CI: 0.28-0.33) as were their families (OR: 0.51; CI: 0.46-0.57). Validated screening tools were less often used in hospitals for assessment of pain (OR: 0.32; CI: 0.30-0.34) or other symptoms (OR: 0.31; CI: 0.28-0.34) despite similar levels of EOL symptoms. Prescriptions of as needed drugs against anxiety (OR: 0.27; CI: 0.24-0.30), nausea (OR: 0.19; CI: 0.17-0.21), or pulmonary secretions (OR: 0.29; CI: 0.26-0.32) were less prevalent in hospitals. Bereavement support was offered after 57% of hospital deaths compared to 87-97% in palliative care units and 72% in nursing homes. CONCLUSIONS: Dying in hospital was associated with inferior end-of-life care quality among cancer patients in Sweden.