Improving Overall Care at the End of Life
Demand is growing for improved end-of-life care and involvement of palliative care teams in the intensive care unit (ICU) and acute care inpatient setting. Indeed, many hospitals have already developed their own programs, and a newly published systematic review found that these hospitals and their practices have much in common already.
The authors propose the development of an algorithm that can be widely used, based on the practices that have already been advocated by experts and proven successful in several institutions that have improved such care.
The systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud, from their inception until March 28, 2019, included 10 publications including clinical practice guidelines, consensus statements, and benchmarks for quality.
Two investigators performed study selection, methodological quality, and data extraction. Four investigators completed quality assessment using the Appraisal of Guidelines for Research and Evaluation II instrument. Recommendations were synthesized and categorized.
Although the applicability and rigor of development indicated low scores in various quality domains, most documents were in agreement on 5 topics:
1. Use of a quantitative tool for pain assessment;
2. Administration of narcotics for pain relief and benzodiazepines for anxiety;
3. No neuromuscular blockers during withdrawal of life support, in order to be able to assess pain;
4. Use of high doses of opioids and sedatives for pain control, regardless of the risk that death might be hastened; and
5. Addition of quality indicators to improve pain management during end-of-life care in the ICU.
The authors concluded that recommendations for pain management at the end-of-life care in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Demand for the involvement of palliative care teams in the management of the dying patients in the ICU is growing. There is a need to clearly define their role in this setting.
Early involvement of the team is necessary and further development of comprehensive evidence-based pain management strategies indicated. Based on the study findings, the authors propose a management algorithm to improve the overall care of dying critically ill patients. (See Duran-Crane A, Laserna A, Lopez-Olivo MA, et al. Clinical practice guidelines and consensus statements about pain management in critically ill end-of-life patients: a systematic review [published online ahead of print September 12, 2019]. Crit Care Med. doi:10.1097/CCM.0000000000003975.)
Sprifermin May Increase Joint Cartilage Thickness in Patients With Osteoarthritis
For the treatment of knee arthritis, results were promising but the clinical significance is still unclear after a study on injection of the investigational drug sprifermin, also known as recombinant human fibroblast growth factor 18, a recombinant form of human fibroblast growth factor 18, to treat knee osteoarthritis.
Sprifermin is under investigation as a disease-modifying osteoarthritis drug currently under investigation for its effects on changes in total femorotibial joint cartilage thickness in patients with severe symptomatic knee osteoarthritis.
The study, called FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses), was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites from July 2013 to May 20117. Participants who enrolled were between the ages of 40 and 85 years, with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. The primary outcome was reported at 2 years and a follow-up analysis at 3 years (not reported).
Participants were randomized: gp 1 intra-articular injections of 100 [micro]g of sprifermin administered every 6 months (n = 110) or, gp 2, every 12 months (n = 110), gp 3, 30 [micro]g of sprifermin every 6 months (n = 111) or, gp 4, every 12 months (n = 110), or placebo every 6 months (n = 108).
Primary end point was change in total femorotibial joint cartilage thickness, as measured by quantitative MRI at 2 years. Secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.
Of 549 participants [median age, 65.0 years; 379 female (69.0%)], 474 (86.3%) completed the 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm [95% confidence interval (CI), 0.03 to 0.07 mm] in gp 1, 0.04 mm (95% CI, 0.02 to 0.06 mm) in gp 2, 0.02 mm (95% CI, -0.01 to 0.04 mm), and in gps 3 and 4, 0.01 mm (95% CI, -0.01 to 0.03 mm).
Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 [micro]g of sprifermin administered every 6 months or every 12 months, or for 30 [micro]g of sprifermin every 6 months or every 12 months.
The most frequently reported treatment-emergent adverse event was arthralgia [placebo: n = 46 (43.0%), gp 1, n = 45 (41.3%), gp 2, n = 50 (45.0%), gp 3, n = 40 (36.0%), and gp 4, n = 48 (44.0%).
The researchers concluded that, in patients with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 [micro]g of sprifermin every 6 or 12 months versus placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 [micro]g of sprifermin every 6 or 12 months versus placebo. Durability of response also was uncertain. http://ClinicalTrials.gov Identifier: NCT01919164. (See: Hochberg MC, Ali Guermazi A, Guering H, et al. Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial. JAMA. 2019;322(14):1360-1370. doi:10.1001/jama.2019.14735.)