We compare the efficacy and adverse effects of 5 oral analgesics in emergency department (ED) patients aged 21 to 64 years with acute musculoskeletal pain.
This was a randomized clinical trial ...conducted in 2 urban EDs. Patients received 400 mg ibuprofen/1,000 mg acetaminophen, 800 mg ibuprofen/1,000 mg acetaminophen, 30 mg codeine/300 mg acetaminophen, 5 mg hydrocodone/300 mg acetaminophen, or 5 mg oxycodone/325 mg acetaminophen. The primary outcome was change in pain before administration of medication (baseline) to 1 hour postbaseline. A numeric rating scale was used, varying from 0=“no pain” to 10=“worst imaginable pain.” Secondary outcomes included receipt of rescue medication and adverse effects at 1 and 2 hours postbaseline. ANOVA was used to test differences in the primary outcome between treatment groups.
Six hundred participants, predominantly men and Latino, were enrolled. Change in pain from baseline to 60 minutes did not differ by treatment (P=.69). The mean change in pain in numeric rating scale units was 400 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% confidence interval CI 2.6 to 3.5); 800 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% CI 2.5 to 3.5), 30 mg codeine/300 mg acetaminophen 3.4 (95% CI 2.9 to 3.9), 5 mg hydrocodone/300 mg acetaminophen 3.1 (95% CI 2.7 to 3.5), and 5 mg oxycodone/325 mg acetaminophen 3.3 (95% CI 2.8 to 3.7). Rescue medication was received before 1 hour had elapsed by 2 patients receiving 400 mg ibuprofen/1,000 mg acetaminophen (1.7%), 3 patients receiving 800 mg ibuprofen/1,000 mg acetaminophen (2.5%), zero patients receiving 30 mg codeine/300 mg acetaminophen (0.0%), 3 patients receiving 5 mg hydrocodone/300 mg acetaminophen (2.5%), and zero patients receiving 5 mg oxycodone/325 mg acetaminophen (0.0%) (P=.21). More patients who received opioids were nauseated or vomited compared with those who did not: 6.7% versus 1.7% (5.0% difference; 95% CI 1.7% to 8.2%). The findings at 2 hours were similar.
No analgesic was more efficacious than others 1 or 2 hours after baseline. There was significantly more nausea and vomiting among patients treated with opioids.
Autophagy, a homeostatic pathway upregulated during cellular stress, is decreased in osteoarthritic chondrocytes and this reduction in autophagy is thought to contribute to the development and ...progression of osteoarthritis (OA). The adenosine A2A receptor (A2AR) is a potent anti-inflammatory receptor and deficiency of this receptor leads to the development of OA in mice. Moreover, treatment using liposomally conjugated adenosine or a specific A2AR agonist improved joint scores significantly in both rats with post-traumatic OA (PTOA) and mice subjected to a high fat diet obesity induced OA. Importantly, A2AR ligation is beneficial for mitochondrial health and metabolism in vitro in primary and the TC28a2 human cell line. An additional set of metabolic, stress-responsive, and homeostatic mediators include the Forkhead box O transcription factors (FoxOs). Data has shown that mouse FoxO knockouts develop early OA with reduced cartilage autophagy, indicating that FoxO-induced homeostasis is important for articular cartilage. Given the apparent similarities between A2AR and FoxO signaling, we tested the hypothesis that A2AR stimulation improves cartilage function through activation of the FoxO proteins leading to increased autophagy in chondrocytes. We analyzed the signaling pathway in the human TC28a2 cell line and corroborated these findings in vivo in a metabolically relevant obesity-induced OA mouse model. We found that A2AR stimulation increases activation and nuclear localization of FoxO1 and FoxO3, promotes an increase in autophagic flux, improves metabolic function in chondrocytes, and reduces markers of apoptosis in vitro and reduced apoptosis by TUNEL assay in vivo. A2AR ligation additionally enhances in vivo activation of FoxO1 and FoxO3 with evidence of enhanced autophagic flux upon injection of the liposome-associated A2AR agonist in a mouse obesity-induced OA model. These findings offer further evidence that A2AR may be an excellent target for promoting chondrocyte and cartilage homeostasis.
Abstract Background A total of 2.7 million patients present to US emergency departments annually for management of low back pain (LBP). Despite optimal medical therapy, more than 50% remain ...functionally impaired 3 months later. We performed a systematic review to address the following question: Among patients with nonchronic LBP, does spinal manipulation, massage, exercise, or yoga, when combined with standard medical therapy, improve pain and functional outcomes more than standard medical therapy alone? Methods We used published searches to identify relevant studies, supplemented with our own updated search. Studies were culled from the Cochrane Register of Controlled Trials, Medline, EMBASE, CINAHL, and the Index to Chiropractic Literature. Our goal was to identify randomized studies that included patients with nonradicular LBP of <12 weeks’ duration that compared the complementary therapy to usual care, sham therapy, or interventions known not to be efficacious, while providing all patients with standard analgesics. The outcomes of interest were improvement in pain scores or measures of functionality. Results We identified 2 randomized controlled trials in which chiropractic manipulation + medical therapy failed to show benefit vs medical therapy alone. We identified 4 randomized controlled trials in which exercise therapy + medical therapy failed to show benefit vs medical therapy alone. We did not identify any eligible studies of yoga or massage therapy. Conclusions In conclusion, for patients with nonchronic, nonradicular LBP, available evidence does not support the use of spinal manipulation or exercise therapy in addition to standard medical therapy. There is insufficient evidence to determine if yoga or massage is beneficial.
We conducted a randomized study to compare the efficacy and adverse event profile of 1,000 mg of intravenous acetaminophen to that of 0.5 mg of intravenous hydromorphone among patients aged 65 years ...or more with acute pain of severity that was sufficient enough to warrant intravenous opioids.
This randomized comparative effectiveness study with 162 participants was conducted in 2 urban emergency departments (EDs). The primary outcome was an improvement in a 0 to 10 pain scale from baseline to 60 minutes later. Secondary outcomes included the need for additional analgesic medication and adverse events that were attributable to the investigational medication. The minimum clinically important difference was an improvement of 1.3 on the 0 to 10 pain scale.
The median baseline pain score was 10 (interquartile range 8 to 10) in both the groups. By 60 minutes, patients taking acetaminophen improved by 3.6 (standard deviation 2.9) on the 0 to 10 pain scale, whereas patients taking hydromorphone improved by 4.6 (standard deviation 3.3) (95% confidence interval CI for the difference of 1.0 was 0.1 to 2.0). Additional analgesic medications were required for 37 (46%) of 81 patients taking acetaminophen and 31 (38%) of 81 patients taking hydromorphone (95% CI for the rounded difference of 7% was −8% to 23%). Adverse events were reported by 6 (7%) of 81 patients taking acetaminophen and 10 (12%) of 81 patients taking hydromorphone (95% CI for the difference of 5% was −4% to 14%) and included dizziness, drowsiness, headache, and nausea.
Although 0.5 mg of the intravenously administered hydromorphone was statistically superior to 1,000 mg of intravenous acetaminophen administered in older patients with acute severe pain in the ED, this difference was not clinically significant. Regardless of the medication received, many participants experienced minimal or incomplete pain relief.
Incision and drainage (I&D) of abscesses is one of the most painful procedures performed in emergency departments (EDs).
We tested the following hypothesis: The addition of intranasal fentanyl to the ...standard practice of local infiltration with lidocaine would provide better pain control than lidocaine alone for adult ED patients undergoing I&D.
This was a randomized, double-blind study. Participants received 2 μg/kg of intranasal fentanyl or a comparable amount of intranasal water in addition to local lidocaine infiltration. The primary outcome, which we assessed immediately after the I&D was completed, was a summary 0–10 pain score for which we asked study subjects to provide a number depicting their entire experience with the procedure.
During a 19-month enrollment period, we screened 176 patients for eligibility and enrolled 49; 25 received placebo and 24 received fentanyl. Baseline characteristics were comparable. Mean (standard deviation) summary pain scores were as follows: fentanyl 6.2 (3.3) and placebo 7.0 (3.2). The 95% confidence interval for a rounded between-group difference of 0.9 was –1.1 to 2.6.
In this small study, the addition of intranasal fentanyl did not substantially impact the pain scores of ED patients undergoing I&D.
Patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and skeletal muscle relaxants. We compare functional outcomes and pain among patients with acute low back pain ...who were randomized to a 1-week course of ibuprofen plus placebo versus ibuprofen plus 1 of 3 skeletal muscle relaxants: baclofen, metaxalone, and tizanidine.
This was a randomized, double-blind, parallel-group, 4-arm study conducted in 2 urban emergency departments (EDs). Patients with nonradicular low back pain for less than or equal to 2 weeks were eligible if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a 24-item inventory of functional impairment caused by low back pain. All participants received 21 tablets of ibuprofen 600 mg, to be taken 3 times a day as needed. Additionally, they were randomized to baclofen 10 mg, metaxalone 400 mg, tizanidine 2 mg, or placebo. Participants were instructed to take 1 or 2 of these capsules 3 times a day as needed. All participants received a 10-minute educational session. The primary outcome was improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1week later. Secondary outcomes included pain intensity 1 week after ED discharge (severe, moderate, mild, or none).
Three hundred twenty patients were randomized. One week later, the mean Roland-Morris Disability Questionnaire score of patients randomized to placebo improved by 11.1 points (95% confidence interval CI 9.0 to 13.3), baclofen by 10.6 points (95% CI 8.6 to 12.7), metaxalone by 10.1 points (95% CI 8.0 to 12.3), and tizanidine by 11.2 points (95% CI 9.2 to 13.2). At 1-week follow-up, 30% of placebo patients (95% CI 21% to 41%) reported moderate to severe low back pain versus 33% of baclofen patients (95% CI 24% to 44%), 37% of metaxalone patients (95% CI 27% to 48%), and 33% of tizanidine patients (95% CI 23% to 44%).
Adding baclofen, metaxalone, or tizanidine to ibuprofen does not appear to improve functioning or pain any more than placebo plus ibuprofen by 1 week after an ED visit for acute low back pain.
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