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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'.)
Concurrent benzodiazepines in opioid-using patients and overdose risk (April 2017)
Benzodiazepines can potentiate the respiratory depressant effects of opioid medication, and concurrent use may be a factor in the rising rate of opioid overdose. In an analysis of a large sample of patients prescribed an opioid, the proportion who concurrently received a benzodiazepine nearly doubled over 12 years . Concurrent use of both medications was associated with an increased risk of opioid overdose compared with patients receiving only the opioid. Avoiding this medication combination may prevent some overdoses. (See "Prevention of lethal opioid overdose in the community", section on 'Risk factors'.)
Naldemedine for opioid-induced constipation (March 2017)
The benefit of naldemedine, an oral peripherally acting opioid receptor antagonist, for opioid-induced constipation (OIC) was shown in two identically designed 12-week phase III randomized trials conducted in patients with noncancer chronic pain and OIC . In a preliminary report, naldemedine, compared with placebo, decreased constipation and was well tolerated with no signs or symptoms of opioid withdrawal or decrease in opioid analgesic efficacy. Naldemedine has been approved in the United States for OIC in adult patients with chronic noncancer pain . However, efficacy has also been shown for treatment of OIC in cancer patients , and naldemedine can be used off label in this population. The European Medicines Agency has approved naldemedine for treatment of OIC without restriction to noncancer pain . (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Other oral agents'.)
Telotristat for refractory carcinoid syndrome diarrhea (March 2017)
Telotristat inhibits the production of serotonin by carcinoid tumors and reduces the frequency of carcinoid syndrome diarrhea. The randomized TELESTAR trial compared two doses of oral telotristat (250 mg and 500 mg, each taken three times daily) against placebo in 135 patients who had uncontrolled symptoms from carcinoid syndrome despite treatment with a somatostatin analog . Treatment with telotristat at either dose was associated with a reduction in bowel movement frequency compared with placebo, and the drug was well tolerated. Based upon these results, telotristat has been approved in the United States, in combination with somatostatin analog therapy, for the treatment of adults with diarrhea related to carcinoid syndrome that is inadequately controlled by somatostatin analog therapy alone . The recommended dose is 250 mg three times daily . (See "Treatment of the carcinoid syndrome", section on 'Telotristat'.)
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 castration-resistant 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'.)
SELECTED END-STAGE CONDITIONS
Decision aids for advance care planning in dementia (February 2017)
Structured interventions to improve advance care planning among families of patients with advanced dementia have not been well studied. In a cluster randomized trial, use of a video decision aid and structured family meeting resulted in better communication about end of life care, greater use of medical orders defining scope of treatment, and fewer hospital transfers compared with a control intervention (informational video and usual care plan meeting) . Audiovisual decision aids and structured meetings may thus be effective components of multidimensional decision-making support for families of patients with advanced dementia. (See "Palliative care of patients with advanced dementia", section on 'Advance care planning'.)
- 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.
- Sun EC, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ 2017; 356:j760.
- Hale ME, Wild J, Reddy J, et al. Efficacy and Safety of Naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy: results from two Phase 3 clinical trials (abstract 598). Data presented at the 2016 Digestive Disease Week, San Diego, CA, May 21, 2016. Abstract available online at http://www.gastrojournal.org/article/S0016-5085(16)30515-7/pdf (Accessed on March 30, 2017).
- https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/208854Orig1s000ltr.pdf (Accessed on March 30, 2017).
- Katakami N, Oda K, Tauchi K, et al. Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients With Cancer. J Clin Oncol 2017; :JCO2016708453.
- http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001893-PIP01-15/pip_001533.jsp&mid=WC0b01ac058001d129 (Accessed on March 30, 2017).
- Kulke MH, Hörsch D, Caplin ME, et al. Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. J Clin Oncol 2017; 35:14.
- https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544035.htm (Accessed on March 03, 2017).
- http://www.xermelo.com/Media/Default/pdfs/Product_Info_telotristat_etiprate.pdf (Accessed on March 03, 2017).
- 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.
- Hanson LC, Zimmerman S, Song MK, et al. Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial. JAMA Intern Med 2017; 177:24.