Optimizing the Dosing Regimen During Rotation From Subcutaneous to Transdermal Administration of Fentanyl.

CONTEXT: Subcutaneous (SC) administration of fentanyl allows for rapid dose titration to treat urgent cancer-related pain. After establishing the optimal fentanyl dose, patients typically rotate towards transdermal (TD) fentanyl patches. Continuing the SC fentanyl up to 12h after application of the patch led to elevated fentanyl concentrations and fentanyl-related toxicities. Based on these findings, and simulations using a pharmacokinetic (PK) model, SC fentanyl administration was discontinued immediately following the application of the patch. OBJECTIVES: To validate the fentanyl rotation schedule by assessing the PK equivalence in fentanyl exposure before and after rotation. METHODS: PK samples and clinical data were prospectively collected from 12 hours prior to rotation until 12 hours after rotation in patients with cancer-related pain undergoing fentanyl rotation. RESULTS: Between December 2021 and September 2023, 29 evaluable patients were enrolled in the study. The 90% confidence interval (CI) of the geometric mean ratio between the post- over pre-rotation area under the curve (AUC) fell within the prespecified 0.8-1.25 equivalence interval (90% CI 1.05-1.16). Patient-reported intensity of both nausea (P = 0.047) and transpiration (P = 0.034) decreased post-rotation. Pain intensity and other adverse events did not differ significantly pre and post-rotation. One patient needed adjustment of opioid therapy 40 hours after rotation due to fentanyl-related toxicities. CONCLUSION: The updated rotation scheme, implying a 1:1 dose conversion and discontinuation of SC fentanyl directly after rotation, resulted in equivalent fentanyl exposure pre and post-rotation. Moreover, the dosing regimen showed to be safe and efficacious during rotation. The new dosing regimen when rotating from SC to TD fentanyl can be effectively and safely implemented in routine palliative care.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Use of potentially inappropriate medication in older patients with lung cancer at the end of life.

OBJECTIVES: Medications at the end of life should be used for symptom control. Medications which potential adverse effects outweigh their expected benefits are called 'potentially inappropriate medications' (PIMs). PIMs are related with adverse drug events and reduced quality of life. In this study, we investigated to what extent PIMs are dispensed to older patients with lung cancer in the last month of life. METHODS: We selected patients with lung cancer, aged 65+, diagnosed between 2009 and 2014, and who died before April 1st 2015 from the population-based Netherlands Cancer Registry (NCR). The NCR is linked to the PHARMO Database Network, that includes medications dispensed by community pharmacies in the Netherlands. The eight PIM groups were based on the OncPal Deprescribing Guideline: aspirin, dyslipidaemia medications, antihypertensives, osteoporosis medications, peptic ulcer prophylaxis, oral hypoglycaemics, vitamins and minerals. RESULTS: Data of 7864 patients with lung cancer were analyzed. Median age was 74 year (IQR = 70-79) and 67% was male. 45% of all patients received at least one PIM in their last month of life. Taking into account all dispensed medications, patients receiving PIMs received more different medications compared to those receiving no PIMs, respectively 10 (SD = 5) vs. 3 (SD = 4) different medications (P < 0.001). CONCLUSION: Almost half of the older patients with lung cancer in the Netherlands received PIMs in their last month of life. Since PIM use is associated with reduced quality of life, it is important that health care professionals continue to critically assess which medication can be discontinued at the end of life.

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.

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.

[A man with a black oesophagus]. / Een man met een zwarte slokdarm.

An 85-year-old man came to the emergency room because of vomiting a black fluid and melaena. He was hypotensive and had severe anaemia. We suspected an upper digestive tract bleeding and an gastroscopy was performed, which showed necrosis of the entire oesophagus. Within 24 hours of admission the patient died of hypovolemic shock.

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.

[Palliative care for a homeless person]. / Palliatieve zorg voor een dakloze.

Homeless people have substantial health disadvantages as compared to the general population, and excessive losses in life expectancy. High proportions of psychiatric disorders, substance abuse and intellectual disability have been reported. This makes palliative care for this population extremely complex. A 55-year-old man, addicted to heroin and cocaine, was diagnosed with metastatic lung cancer. His terminal phase of life was complicated by many admissions to different care settings and problems with symptom management. Involvement of a palliative care consultation team and transfer to a homeless shelter, to which homeless people with life-threatening diseases could be admitted, gave both the patient and his family relief. This case illustrates that palliative care in homeless patients may be extremely complex due to the specific physical and psychosocial features involved. Such care should be offered proactively and on a multidisciplinary basis.

Oromandibular dystonia: a serious side effect of capecitabine.

BACKGROUND: Capecitabine has activity against several types of cancer. In 10-15% of patients treated with capecitabine, treatment is discontinued because of serious adverse reactions, mostly within the first weeks of treatment. CASE PRESENTATION: A 56 year-old female patient presented at the emergency department after ten days of chemotherapy with progressive airway obstruction and complaints of numbness of the tongue. She also had difficulty swallowing and was unable to speak. Laboratory findings were completely normal and no co-medication was used, in particular no dopamine antagonists. CONCLUSION: The case highlights the need for awareness that capecitabine may potentially lead to severe life-threatening complaints of oromandibular dystonia. We hypothesize that capecitabine passed the blood brain barrier which led to a disruption within the basal ganglia in this case. Prompt treatment with an anticholinergic drug and cessation of capecitabine in the patient case led to disappearance of complaints.

A child with severe hearing loss associated with maternal cisplatin treatment during pregnancy.

BACKGROUND: Cisplatin is considered safe to use during the second and third trimesters of pregnancy in patients with cancer. CASE: A 34-year-old pregnant woman was diagnosed with cervical cancer. She received five weekly dosages of cisplatin and paclitaxel, starting at 26 5/7 weeks of gestation. An elective cesarean delivery was performed at 34 4/7 weeks of gestation. After birth, the neonate was diagnosed with severe bilateral perceptive hearing loss. CONCLUSION: Cisplatin during the second and third trimesters of pregnancy may lead to fetal ototoxicity.