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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
GENERAL PRINCIPLES OF PALLIATIVE CARE
Early initiation of palliative care and survival (February 2017)
When initiated early in the disease course, palliative care improves clinical and quality of care outcomes; randomized trials in patients with cancer or advanced lung disease also report a survival advantage, although more diverse palliative care populations have not been studied. A meta-analysis of seven randomized trials involving 2184 patients concluded that there was no association between early initiation of palliative care and overall survival . Previous reports of a possible survival advantage may have reflected bias in patient selection; only one of the seven trials was rated as having a low risk of bias. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
Palliative care during hematopoietic cell transplantation (February 2017)
For patients with serious life-threatening illness, comprehensive palliative care can be successfully integrated with disease-modifying treatment. The benefits of delivering palliative care alongside potentially curative treatment were shown in a randomized trial of inpatient palliative care consultation versus usual transplant care in 160 adults with hematologic malignancies undergoing autologous or allogeneic hematopoietic cell transplantation . At two weeks posttransplant, the increase in depression, anxiety, and overall symptom burden was less in the intervention group, and the decrease in quality of life (QOL) was also smaller. Depression and QOL benefits persisted at three months. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
ASCO recommendations on palliative care in patients with advanced cancer (November 2016)
In response to increasing evidence from randomized trials that early palliative care offers benefits in terms of quality of life, mood, end-of-life care, and possibly even survival, an updated provisional clinical opinion from the American Society of Clinical Oncology (ASCO) now recommends integrating dedicated palliative care services into the care of inpatients and outpatients with advanced cancer early in the disease course, concurrent with active treatment . Essential components of palliative care may include symptom, distress, and functional status management; clarification of treatment goals; assistance with medical decision making; coordination with other care providers; and assessment and support of coping needs. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
Antipsychotics for delirium in terminally ill patients (January 2017)
The benefit of antipsychotics for management of delirium in terminally ill patients has been called into question by a randomized trial in which 247 inpatients of a hospice or palliative care service with mild to moderately severe delirium were assigned to oral risperidone, haloperidol, or placebo every 12 hours for 72 hours . All patients received individualized supportive care. Patients who received antipsychotics had more severe delirium, worse delirium-associated distress scores, more use of midazolam, more extrapyramidal effects, and worse short-term survival. In our view, this study does not justify abandoning the use of antipsychotics for severely agitated delirious patients but points to the importance of reversing precipitating causes, providing best supportive care for symptomatic distress associated with delirium, and the need for additional research on the use of antipsychotics. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Treatment'.)
Dosing interval for zoledronic acid in patients with bone metastases (January 2017)
For patients with bone metastases from a solid tumor, the approved dose and schedule of administration for zoledronic acid to reduce the frequency of skeletal-related events (SREs) is 4 mg every three to four weeks. Less frequent dosing is supported by data from CALGB (Alliance) trial 70604, which randomly assigned 1822 patients with bone metastases from breast or prostate cancer or multiple myeloma to the same dose of zoledronic acid every 4 or every 12 weeks for two years, starting with the first dose. There was no difference in the proportion of patients who developed at least one SRE (29.5 versus 28.6 percent) . There are now sufficient data in breast and prostate cancer to support dosing of zoledronic acid every 12 rather than every 4 weeks, and we suggest this approach for most patients. We still prefer every-four-week dosing, at least initially, for patients who have extensive or highly symptomatic bone metastases. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Dosing interval'.)
Updated MASCC/ESMO guidelines for nausea and emesis related to cancer treatment (October 2016)
Updated guidelines for prevention and management of cancer therapy-associated nausea and vomiting are available from the Multinational Association of Supportive Care in Cancer and the European Society of Medical Oncology (table 1), the consensus panel also provides guidance on the use of prophylactic antiemetics in patients undergoing radiation therapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Recommendations for specific groups'.)
Olanzapine for prevention of nausea and vomiting induced by highly emetogenic chemotherapy regimens (August 2016)
The antipsychotic olanzapine may be a particularly useful agent for preventing delayed chemotherapy-induced nausea and vomiting, which is often poorly controlled with conventional antiemetics. The effectiveness of adding olanzapine to a standard antiemetic regimen was shown in a trial in which 380 patients receiving highly emetogenic chemotherapy (cisplatin or doxorubicin/cyclophosphamide for breast cancer) were randomly assigned to dexamethasone, an NK1R antagonist, and a 5-HT3 receptor antagonist plus either olanzapine (10 mg daily orally on days 1 through 4) or placebo . The proportion of patients with no chemotherapy-induced nausea (the primary endpoint) was higher with olanzapine both in the first 24 hours after chemotherapy and in the delayed period. Rates of complete response (no emesis and no use of rescue medication) were also higher with olanzapine over a five-day period. Patients receiving olanzapine had more sedation on day 2 (severe in 5 percent), which resolved despite continued olanzapine. On the basis of this trial, we now suggest the addition of olanzapine on days 1 through 4 to standard antiemetic therapy for patients receiving highly emetogenic chemotherapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)
SELECTED END-STAGE CONDITIONS
Potential interaction between high-dose methotrexate and levetiracetam (November 2016)
Levetiracetam is sometimes used for prophylaxis and treatment of seizures in patients undergoing high-dose methotrexate (MTX) treatment for brain or other central nervous system (CNS) cancers, including lymphomas. Health Canada has issued a safety review describing a potential interaction between the two drugs, noting 13 reports received by the levetiracetam manufacturer and concluding that concurrent use can lead to significantly elevated levels of MTX and increased risk of toxicity . The labeling is being revised to recommend careful MTX blood level monitoring. Additional details are available from Lexi-Interact, the drug interactions tool included within UpToDate. (See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Coadministered drugs that may interfere with excretion'.)
Proton pump inhibitors may diminish capecitabine efficacy (October 2016)
Two recent studies suggest that proton pump inhibitors diminish the effectiveness of capecitabine in the treatment of colorectal and gastroesophageal cancer [9,10]. It is hypothesized that higher gastric pH levels may inhibit dissolution and absorption of capecitabine. Patients who are receiving a capecitabine-containing regimen for adjuvant treatment of colon cancer or other malignancies should, when possible, avoid taking concurrent proton pump inhibitors. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Capecitabine'.)
Declining use of feeding tubes in advanced dementia (August 2016)
Patients with advanced dementia commonly have eating problems in the final stages of illness, and caregivers are faced with decisions about whether to continue oral feeding by hand or place a long-term feeding tube. The available evidence fails to demonstrate any health benefits of tube feeding over ongoing hand feeding, and an increasing number of consensus-based guidelines advocate against feeding tube placement in this setting. In keeping with these recommendations, a recent study in the United States found that the proportion of nursing home residents with advanced dementia who received a feeding tube within one year of the onset of feeding problems decreased by approximately 50 percent between the years 2000 and 2014 . Advance care planning is critical in the management of patients with dementia and should include preparatory discussions about eating problems and other common complications encountered in the advanced stages of the disease. (See "Palliative care of patients with advanced dementia", section on 'Oral versus tube feeding'.)
Use of adjunctive antidepressants for treating complicated grief with comorbid depression (August 2016)
Complicated grief is a distinct syndrome that often occurs in bereaved individuals and is characterized by maladaptive thoughts, dysfunctional behaviors, and poorly regulated emotions. The best treatment for complicated grief is psychotherapy that is specific for complicated grief (complicated grief therapy, CGT). Antidepressants are frequently prescribed as an adjunctive therapy. Although adjunctive antidepressants do not appear to mitigate symptoms of complicated grief, they can improve comorbid unipolar major depression, which is common. In a recent trial, 395 adults with complicated grief were randomly assigned to citalopram alone, placebo alone, CGT plus citalopram, or CGT plus placebo . As expected, more patients responded to CGT plus placebo than placebo alone. The addition of citalopram did not significantly improve complicated grief outcomes. However, improvement of depressive symptoms was greater with citalopram. Thus, in patients with complicated grief and depressive symptoms, the addition of citalopram may be helpful. (See "Complicated grief in adults: Treatment", section on 'Other options'.)
- Kavalieratos D, Corbelli J, Zhang D, et al. Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis. JAMA 2016; 316:2104.
- El-Jawahri A, LeBlanc T, VanDusen H, et al. Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial. JAMA 2016; 316:2094.
- Ferrell BR, Temel JS, Tenin J. Integration of palliative care. J Clin Oncol 2016.
- Agar MR, Lawlor PG, Quinn S, et al. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med 2017; 177:34.
- Himelstein AL, Foster JC, Khatcheressian JL, et al. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA 2017; 317:48.
- Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 2016; 27:v119.
- Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 2016; 375:134.
- http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/levetiracetam-eng.php (Accessed on October 28, 2016).
- Chu MP, Hecht JR, Slamon D, et al. Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer: Secondary Analysis of the TRIO-013/LOGiC Randomized Clinical Trial. JAMA Oncol 2016.
- Sun J, Ilich AI, Kim CA, et al. Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients. Clin Colorectal Cancer 2016; 15:257.
- Mitchell SL, Mor V, Gozalo PL, et al. Tube Feeding in US Nursing Home Residents With Advanced Dementia, 2000-2014. JAMA 2016; 316:769.
- Shear MK, Reynolds CF 3rd, Simon NM, et al. Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial. JAMA Psychiatry 2016; 73:685.