Physicians' Opinions on Anticoagulant Therapy in Patients with a Limited Life Expectancy.

Patients with a limited life expectancy have an increased risk of thromboembolic and bleeding complications. Anticoagulants are often continued until death, independent of their original indication. We aimed to identify the opinions of physicians about the use of anticoagulants at the end of life. A mixed-method research design was used. A secondary analysis was performed on data from a vignette study and an interview study. Participants included general practitioners and clinical specialists. Physicians varied in their opinions: some would continue and others would stop anticoagulants at the end of life because of the risk of thromboembolic or bleeding complications. The improvement or preservation of patients' quality of life was a reason for both stopping and continuing anticoagulants. Other factors considered in the decision-making were the types of anticoagulant, the indication for which the anticoagulant was prescribed, underlying diseases, and the condition and life expectancy of the patient. Factors that made decision-making difficult were the lack of evidence on either strategy, uncertainty about patients' life expectancy, and the fear of harming patients. Which decision was eventually made seems largely dependent on the choice of the patient. In conclusion, there is a substantial variation in physicians' opinions regarding the use of anticoagulants in patients with a limited life expectancy. Physicians agree that the primary goal of medical care at end of life is the improvement or preservation of patients' quality of life. An important barrier to decision-making is the lack of evidence about the risks and benefits of stopping anticoagulants.

Use of antithrombotics at the end of life: an in-depth chart review study.

BACKGROUND: Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients' quality of life, the use of antithrombotics should be reconsidered. METHODS: We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease. RESULTS: In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics. CONCLUSIONS: Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.

Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: The SILENCE Randomized Clinical Trial.

Importance: Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical guidelines recommend anticholinergic drugs to reduce the death rattle after nonpharmacological measures fail, evidence regarding their efficacy is lacking. Given that anticholinergics only decrease mucus production, it is unknown whether prophylactic application may be more appropriate. Objective: To determine whether administration of prophylactic scopolamine butylbromide reduces the death rattle. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled trial was performed in 6 hospices in the Netherlands. Patients with a life expectancy of 3 or more days who were admitted to the participating hospices were asked to give advance informed consent from April 10, 2017, through December 31, 2019. When the dying phase was recognized, patients fulfilling the eligibility criteria were randomized. Of the 229 patients who provided advance informed consent, 162 were ultimately randomized. The date of final follow-up was January 31, 2020. Interventions: Administration of subcutaneous scopolamine butylbromide, 20 mg four times a day (n = 79), or placebo (n = 78). Main Outcomes and Measures: The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back (range, 0-3; 0, no rattle; 3, rattle audible standing in the door opening) measured at 2 consecutive time points with a 4-hour interval. Secondary outcomes included the time between recognizing the dying phase and the onset of a death rattle and anticholinergic adverse events. Results: Among 162 patients who were randomized, 157 patients (97%; median age, 76 years [IQR, 66-84 years]; 56% women) were included in the primary analyses. A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI, 2%-27%, P = .02). Regarding secondary outcomes, an analysis of the time to death rattle yielded a subdistribution hazard ratio (HR) of 0.44 (95% CI, 0.20-0.92; P = .03; cumulative incidence at 48 hours: 8% in the scopolamine group vs 17% in the placebo group). In the scopolamine vs placebo groups, restlessness occurred in 22 of 79 patients (28%) vs 18 of 78 (23%), dry mouth in 8 of 79 (10%) vs 12 of 78 (15%), and urinary retention in 6 of 26 (23%) vs 3 of 18 (17%), respectively. Conclusions and Relevance: Among patients near the end of life, prophylactic subcutaneous scopolamine butylbromide, compared with placebo, significantly reduced the occurrence of the death rattle. Trial Registration: trialregister.nl Identifier: NTR6264.

Role of nurses in medication management at the end of life: a qualitative interview study.

BACKGROUND: Patients in the last phase of their lives often use many medications. Physicians tend to lack awareness that reviewing the usefulness of medication at the end of patients' lives is important. The aim of this study is to gain insight into the perspectives of patients, informal caregivers, nurses and physicians on the role of nurses in medication management at the end of life. METHODS: Semi-structured interviews were conducted with patients in the last phase of their lives, in hospitals, hospices and at home; and with their informal caregivers, nurses and physicians. Data were qualitatively analyzed using the constant comparative method. RESULTS: Seventy-six interviews were conducted, with 17 patients, 12 informal caregivers, 15 nurses, 20 (trainee) medical specialists and 12 family physicians. Participants agreed that the role of the nurse in medication management includes: 1) informing, 2) supporting, 3) representing and 4) involving the patient, their informal caregivers and physicians in medication management. Nurses have a particular role in continuity of care and proximity to the patient. They are expected to contribute to a multidimensional assessment and approach, which is important for promoting patients' interest in medication management at the end of life. CONCLUSIONS: We found that nurses can and should play an important role in medication management at the end of life by informing, supporting, representing and involving all relevant parties. Physicians should appreciate nurses' input to optimize medication management in patients at the end of life. Health care professionals should recognize the role the nurses can have in promoting patients' interest in medication management at the end of life. Nurses should be reinforced by education and training to take up this role.

Perspectives of patients, close relatives, nurses, and physicians on end-of-life medication management.

ABSTRACTObjective:Our aim was to gain insight into the perspectives of patients, close relatives, nurses, and physicians on medication management for patients with a life expectancy of less than 3 months. METHOD: We conducted an empirical multicenter study with a qualitative approach, including in-depth interviews with patients, relatives, nurses, specialists, and general practitioners (GPs). We used the constant comparative method and ATLAS.ti (v. 7.1) software for our analysis. RESULTS: Saturation occurred after 18 patient cases (76 interviews). Some 5 themes covering 18 categories were identified: (1) priorities in end-of-life care, such as symptom management and maintaining hope; (2) appropriate medication use, with attention to unnecessary medication and deprescription barriers; (3) roles in decision making, including physicians in the lead, relatives' advocacy, and pharmacists as suppliers; (4) organization and communication (e.g., transparency of tasks and end-of-life conversations); and (5) prerequisites about professional competence, accessibility and quality of medical records, and financial awareness. Patients, relatives, nurses, specialists, and GPs varied in their opinions about these themes. SIGNIFICANCE OF RESULTS: This study adds to our in-depth understanding of the complex practice of end-of-life medication management. It provides knowledge about the diversity of the perspectives of patients, close relatives, nurses, and physicians regarding beliefs, attitudes, knowledge, skills, behavior, work setting, the health system, and cultural factors related to the matter. Our results might help to draw an interdisciplinary end-of-life medication management guide aimed at stimulating a multidisciplinary and patient-centered pharmacotherapeutic care approach.

A Tool for Deprescribing Antithrombotic Medication in Palliative Cancer Patients: A Retrospective Evaluation.

Treating palliative cancer patients with antithrombotics is challenging because of the higher risk for both venous thromboembolism and major bleeding. There is a lack of available guidelines on deprescribing potentially inappropriate antithrombotics. We have therefore created an antithrombotics scheme to aid in (de)prescribing antithrombotics. A retrospective single-center clinical cohort observational study was performed to evaluate it. Patients with solid tumors with a life expectancy of less than 3 months seen by the palliative team were included. Comparisons were made between patients who were treated according to the antithrombotics scheme and those who were not. 47.6% of patients used antithrombotics. One hundred and eleven patients were included for analysis. Most patients used antithrombotics according to the scheme (n = 80, 72.1%). Eleven patients experienced a clinical event, seven patients in the scheme adherence group (9.9%) and four in the no scheme adherence group (13.8%), which was not statistically significant (p = 0.726). The higher frequency of clinical events in the group without scheme adherence suggests that (de)prescribing antithrombotics according to the antithrombotics scheme is safe. The results of this study suggest that the antithrombotics scheme could aid healthcare professionals identifying possible inappropriate antithrombotics in palliative cancer patients. Further prospective research is needed to investigate this tool.

Appropriate Timing of End-of-Life Care: A Dutch Policy Analysis and Opportunities for Improvement.

Background: The Exceptional Medical Expenses Act (EMEA) guaranteed public financing for the costs of end-of-life care in The Netherlands until 2015. A life expectancy shorter than three months was a prerequisite for a patient to qualify. Objective: To estimate survival and its potential predictors using the start date of EMEA funded end-of-life care as time origin, and to calculate the ensuing costs. Design: Retrospective observational study using data retrieved from multiple datasets of the national statistical office Statistics Netherlands (https://www.cbs.nl/en-gb/). Setting: Included were all adult patients, who received EMEA funded end-of-life care in hospice units in nursing homes and homes for the elderly in The Netherlands between January 1, 2009, and December 31, 2014. Results: In 40,659 patients (median age 79 years), the distribution of survival was extremely skewed. Median, 95%, and maximum survival times were 15 (95% confidence interval [CI] = 15-15), 219 (210-226), and 2,006 days, respectively. The 90-day and 180-day survival rates were 12.4 (12.1-12.7)% and 6.2 (6.0-6.5)%, respectively. Although age, gender, diagnosis, and start year of end-of-life care were statistically significant independent predictors, clinical significance is limited. End-of-life care was delivered for a total of 1,720,002 days, costing almost 440 million Euros. Fifty-nine percent of the costs was for barely 11% of patients, i.e., those who received end-of-life care for more than 90 days. Conclusion: The use of life expectancy is a weak basis for the appropriate timing of end-of-life care. Further research should evaluate potential tools to improve the timing of end-of-life care, while using available resources efficiently.

Better drug use in advanced disease: an international Delphi study.

Patients with a limited life expectancy use many medications, some of which may be questionable. OBJECTIVES : To identify possible solutions for difficulties concerning medication management and formulate recommendations to improve medication management at the end of life. METHODS : A two-round Delphi study with experts in the field of medication management and end-of-life care (based on ranking in the citation index in Web of Science and relevant publications). We developed a questionnaire with 58 possible solutions for problems regarding medication management at the end of life that were identified in previously performed studies. RESULTS : A total of 42 experts from 13 countries participated. Response rate in the first round was 93%, mean agreement between experts for all solutions was 87 % (range 62%-100%); additional suggestions were given by 51%. The response rate in the second round was 74%. Awareness, education and timely communication about medication management came forward as top priorities for guidelines. In addition, solutions considered crucial by many of the experts were development of a list of inappropriate medications at the end of life and incorporation of recommendations for end-of-life medication management in disease-specific guidelines. CONCLUSIONS : In this international Delphi study, experts reached a high level of consensus on recommendations to improve medication management in end-of-life care. These findings may contribute to the development of clinical practice guidelines for medication management in end-of-life care.

Smartwatch based automatic detection of out-of-hospital cardiac arrest: Study rationale and protocol of the HEART-SAFE project.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Immediate detection and treatment are of paramount importance for survival and good quality of life. The first link in the 'chain of survival' after OHCA - the early recognition and alerting of emergency medical services - is at the same time the weakest link as it entirely depends on witnesses. About one half of OHCA cases are unwitnessed, and victims of unwitnessed OHCA have virtually no chance of survival with good neurologic outcome. Also in case of a witnessed cardiac arrest, alerting of emergency medical services is often delayed for several minutes. Therefore, a technological solution to automatically detect cardiac arrests and to instantly trigger an emergency response has the potential to save thousands of lives per year and to greatly improve neurologic recovery and quality of life in survivors. The HEART-SAFE consortium, consisting of two academic centres and three companies in the Netherlands, collaborates to develop and implement a technical solution to reliably detect OHCA based on sensor signals derived from commercially available smartwatches using artificial intelligence. In this manuscript, we describe the rationale, the envisioned solution, as well as a protocol outline of the work packages involved in the development of the technology.

A pilot study on potential new plasma markers for diagnosis of acute appendicitis.

BACKGROUND: Diagnosis of acute appendicitis (AA) remains a surgical dilemma, with negative appendectomy rates of 5% to 40% and perforation suggestive for late operative intervention in 5% to 30%. The aim of this study is to evaluate new plasma markers, representing early neutrophil activation, to improve diagnostic accuracy in patients suspected for AA. MATERIALS AND METHODS: Fifty-one patients who underwent surgery for AA were included (male-female = 28:23), and blood was sampled. Plasma concentrations of 2 neutrophil proteins were measured: lactoferrin (LF) and calprotectin (CP). Controls consisted of 27 healthy volunteers. C-reactive protein (CRP) and white blood cell count (WBC) concentrations were measured for routine patient care. RESULTS: Median plasma concentrations for LF and CP were significantly higher in 51 patients with proven AA (665 and 766 ng/mL, respectively) than in 27 healthy volunteers (198 and 239 ng/mL, respectively, P < .001). No clinically relevant correlation exists between the plasma levels of LF and CP and the conventional laboratory tests for CRP and WBC. CONCLUSIONS: Circulating LF and CP levels are significantly elevated in patients with appendicitis and are detectable in plasma using relatively simple and low-cost enzyme-linked immunosorbent assays. Furthermore, plasma levels of LF and CP give additional information to conventional markers WBC and CRP, making them potential new markers for AA diagnosis.

Medication Discontinuation at the End of Life: A Questionnaire Study on Physicians' Experiences and Opinions.

BACKGROUND: Many patients who are in the last phase of life use multiple medications that are continued until shortly before they ultimately die. Little is known about physicians' opinions and experiences regarding medication discontinuation at the end of patients' lives. OBJECTIVE: To explore physicians' opinions and experiences regarding medication discontinuation during the last phase of life, and to identify factors influencing the continuation of potentially inappropriate medications. DESIGN: Questionnaire study, including a vignette and several statements. SETTING/SUBJECTS: A random sample of general practitioners and clinical specialists working in three regions in the Netherlands that represent more than half of the Dutch population. RESULTS: Questionnaires were returned by 321 physicians (response rate: 37%). The majority of them (73%) agreed with the statement that patients who are in the last phase of life use too many medications. When presented with a vignette of a patient with end-stage COPD with different limited life expectancies, preventive medications would be stopped right early before death. Medications to relieve symptoms would not be stopped or stopped right before death. For medications to treat (chronic) illnesses, there was a huge interphysician variability. All statements about possible reasons why medications are continued in the last phase of life, for example, patients feeling abandoned and lack of time, were agreed upon by a small minority of respondents. CONCLUSIONS: Although physicians agree that patients use too many medications at the end of life, they quite regularly seem to give patients medications for chronic diseases, for which the benefit at the end of life may be debatable. More scientific evidence on whether or not these types of medication might be discontinued in the last phase of life is needed.

Medication Use in the Last Days of Life in Hospital, Hospice, and Home Settings in the Netherlands.

BACKGROUND: The purpose of medication management in the last days of life is to optimize patient's comfort. Little is known about the medication use in the days before death and how this relates to the care setting. OBJECTIVE: To describe medication use in the last week of life for patients dying in hospital, hospice, and home settings in the Netherlands. DESIGN: Retrospective chart review study. SETTING: A convenience sample of patient records from the three settings in three different regions in the Netherlands that cover more than half the country. MEASUREMENTS: Information about medication use in the last week of life of patients who ultimately died an expected death was registered, including type of medication, start and if applicable stop dates, administration routes, and doses. RESULTS: One hundred seventy-nine records were analyzed. Medications most frequently used in the last week of life were analgesics (n = 168, 94.1%) and psycholeptics (n = 150, 84.7%), in particular by hospice patients. The mean number of medications used per patient was nine during day 7 before death and six on the day of dying. On the day of death, 48 (26.8%) patients used a preventive medication. This percentage was highest for patients dying in the hospital or at home. CONCLUSIONS: Patients who die an expected death receive many medications in the last week of life, part of which are preventive medications. Medication management in patients' final days of life can be improved, especially in the hospital and home setting.