A sequential, multiple-assignment, randomized trial of analgesic strategies for acute musculoskeletal Pain.

BACKGROUND: Most methodologically rigorous, ED-based, comparative effectiveness analgesic studies completed in the last two decades failed to find a clinically important difference between the comparators. We believe that many of these comparative effectiveness studies were biased towards the null hypothesis because some ED patients with intense pain will respond to relatively mild interventions. We hypothesized that including a run-in period would alter the results of an acute pain RCT. METHODS: We conducted a sequential, multiple-assignment, randomized study. Adults with acute moderate/severe musculoskeletal pain were randomized (3:1 ratio) to run-in period or no run-in. We administered 650 mg acetaminophen to run-in participants. Those run-in patients who reported insufficient relief one-hour later were randomized (1:1 ratio) to ibuprofen 800mg PO or ketorolac 20mg PO as were all participants randomized to no run-in. The primary outcome was achieving a clinically important improvement, defined as improvement ≥1.3 on a 0-10 scale. We built a logistic regression model including run-in/no run-in, ketorolac/ibuprofen, age and sex. RESULTS: Of 307 participants who received acetaminophen, 100 (32.6%) reported inadequate relief and were randomized to an NSAID. Of the 100 patients randomized to no run-in, 84/100 (84%) achieved the primary outcome versus 246/287 (86%) run-in participants (95% CI for difference = 2%:-7,10%). Among run-in participants who received an NSAID, 82/99(83%) achieved the primary outcome versus 84/100(84%) no run-in participants (p = 0.82). Among all ibuprofen participants, 44/49(90%) randomized to run-in and 42/50(84%) randomized to no run-in achieved the primary outcome. Among all ketorolac participants, 38/50(76%) randomized to run-in and 42/50 (84%) randomized to no run-in achieved the primary outcome. We observed the following results in a multivariable analysis: OR for ketorolac versus ibuprofen:0.60 (95% CI: 0.28, 1.28); OR for run-in versus no run-in:0.91(95% CI: 0.43, 1.93). CONCLUSIONS: Among patients with acute musculoskeletal pain, using an acetaminophen first strategy did not alter pain outcomes.

Should COVID-19 symptoms be used to cohort patients in the emergency department? A retrospective analysis.

OBJECTIVE: To determine how cohorting patients based on presenting complaints affects risk of nosocomial infection in crowded Emergency Departments (EDs) under conditions of high and low prevalence of COVID-19. METHODS: This was a retrospective analysis of presenting complaints and PCR tests collected during the COVID-19 epidemic from 4 EDs from a large hospital system in Bronx County, NY, from May 1, 2020 to April 30, 2021. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated for a symptom screen based on the CDC list of COVID-19 symptoms: fever/chills, shortness of breath/dyspnea, cough, muscle or body ache, fatigue, headache, loss of taste or smell, sore throat, nasal congestion/runny nose, nausea, vomiting, and diarrhea. PPV was calculated for varying values of prevalence. RESULTS: There were 80,078 visits with PCR tests. The sensitivity of the symptom screen was 64.7% (95% CI: 63.6, 65.8), specificity 65.4% (65.1, 65.8). PPV was 16.8% (16.5, 17.0) and NPV was 94.5% (94.4, 94.7) when the observed prevalence of COVID-19 in the ED over the year was 9.7%. The PPV of fever/chills, cough, body and muscle aches and nasal congestion/runny nose were each approximately 25% across the year, while diarrhea, nausea, vomiting and headache were less predictive, (PPV 4.7%-9.6%) The combinations of fever/chills, cough, muscle/body aches, and shortness of breath had PPVs of 40-50%. The PPV of the screen varied from 3.7% (3.6, 3.8) at 2% prevalence of COVID-19 to 44.3% (44.0, 44.7) at 30% prevalence. CONCLUSION: The proportion of patients with a chief complaint of COVID-19 symptoms and confirmed COVID-19 infection was exceeded by the proportion without actual infection. This was true when prevalence in the ED was as high as 30%. Cohorting of patients based on the CDC's list of COVID-19 symptoms will expose many patients who do not have COVID-19 to risk of nosocomially acquired COVID-19. EDs should not use the CDC list of COVID-19 symptoms as the only strategy to minimize exposure.

Predicting three-month functional outcomes after an ED visit for acute low back pain.

BACKGROUND: Nearly 30% of patients who present to an ED with acute, new onset, low back pain (LBP) report LBP-related functional impairment three months later. These patients are at risk of chronic LBP, a highly debilitating condition. It has been reported previously that functional impairment, depression, and psychosomatic symptomatology at the index visit are associated with poor LBP outcomes. We wished to replicate those findings in a cohort of ED patients, and also to determine if clinical features present at one week follow-up could predict three-month outcomes in individual patients. METHODS: This was a planned analysis of data from a randomized comparative effectiveness study of three analgesic combinations conducted in one ED. Patients were followed by telephone one week and three months post-ED visit. The primary outcome was a three-month Roland-Morris Disability Questionnaire (RMDQ) score >0, indicating the presence of LBP-related functional impairment. At the index visit, we measured functional impairment (using the RMDQ), depressive symptomatology (using the Patient Health Questionnaire depression module), and psychosomatic features (using the 5-item Cassandra scale). At the one-week follow-up, we ascertained the presence or absence of LBP. We built a logistic regression model in which all the predictors were entered and retained in the model, in addition to socio-demographic variables and dummy variables controlling for investigational medication. Results are reported as adjusted odds ratios (adjOR) with 95% CI. To determine if statistically significant associations could be used to predict three-month outcomes in individual patients, we then calculated positive and negative likelihood ratios [LR(+) and LR(-)] with 95% CI for those independent variables associated with the primary outcome. RESULTS: Of 295 patients who completed the study, 14 (5%) were depressed and 18 (6%) reported psychosomatic symptoms. The median index visit RMDQ score was 19 (IQR: 17, 21) indicating substantial functional impairment. One week after the ED visit, 193 (65%) patients reported presence of LBP. 294 patients provided a three-month RMDQ score, 88 of whom (30%, 95% CI: 25, 35%) reported a score >0. Neither depression (adjOR 0.7 [95% CI 0.2, 3.1]), psychosomatic symptomatology (adjOR 0.5 [95% CI 0.1, 2.0]), nor index visit functional impairment (adjOR 1.0 [95% CI 1.0, 1.1]) were associated with three-month outcome. Pain at one week was strongly and independently associated with the three-month outcome when examined at the group level (adjOR 4.0 [95% CI 2.1, 7.7]). However, likelihood ratios for pain or its absence at one-week were insufficiently robust to be clinically useful in predicting three-month outcomes in individual patients (LR+: 1.4 [95% CI: 1.3, 1.7]; LR-: 0.4 [95% CI: 0.2, 0.6]). CONCLUSIONS: In spite of a strong association at the group level between presence of LBP at one week and functional impairment at three months, when used to predict outcomes in individual patients, presence of pain failed to discriminate with clinically meaningful utility between acute LBP patients destined to have a favorable versus unfavorable three-month outcome.

Intravenous fluids for migraine: a post hoc analysis of clinical trial data.

BACKGROUND: A total of 1.2 million patients present to US emergency departments (EDs) annually with migraine headache. Intravenous fluid (IVF) hydration is used to treat acute migraine commonly. We were unable to identify published data to support or refute this practice. The goal of this analysis was to determine if administration of IVF is associated with improved short-term (1 hour) or sustained (24 hours) migraine outcomes. METHODS: This was a post hoc analysis of data collected from 4 ED-based migraine clinical trials in which patients were randomized to treatment with intravenous metoclopramide. In each of these studies, patients were administered IVF at the discretion of the treating physician. Our primary short-term outcome was improvement in 0 to 10 pain scale between baseline and 1 hour later. Our primary sustained outcome was the attainment of sustained headache freedom, defined as achieving a headache level of "none" in the ED and maintaining a level of "none" without headache recurrence throughout the 24- to 48-hour follow-up period. We compared mean improvement in pain scores between baseline and 1 hour later between those patients who received IVF and those who did not. We also compared the frequency of sustained headache freedom between both groups. We then used regression models to elucidate how nausea at baseline and the baseline pain score modified the relationship between IVF and the 2 outcomes. RESULTS: A total of 570 patients were included in the analysis. Of these, 112 (20%) were treated with IVF. Patients who received IVF improved by 4.5 (95% confidence interval [CI], 4.0-5.0) on the 0 to 10 scale, whereas patients who did not receive IVF improved by 5.1 (95% CI, 4.8-5.3) (95% CI for difference of 0.6, 0-1.1). Of patients who received IVF, 14% (95% CI, 9-22%) enjoyed sustained headache freedom vs 18% (95% CI, 15%-22%) of patients who did not (95% CI for difference of 4%, -4% to 11%). In the linear regression model, IVF was associated with less improvement in 0 to 10 pain score between baseline and 1 hour (B coefficient, -0.6; 95% CI, -1.1 to 0; P=.05). In the logistic regression model, IVF administration was not associated with sustained headache freedom (odds ratio, 0.8; 95% CI, 0.4-1.5; P=.52). CONCLUSION: Intravenous fluid did not improve pain outcomes among patients with acute migraine who were treated with intravenous metoclopramide.

Impact of a negative prior stress test on emergency physician disposition decision in ED patients with chest pain syndromes.

OBJECTIVE: Many emergency department (ED) patients with potential acute coronary syndromes (ACS) have prior visits and prior cardiac testing; however, the effect of knowledge of prior testing on the emergency physician disposition decision making is not known. We studied the impact of prior noninvasive testing (ie, stress testing) for myocardial ischemia on disposition decision making in ED patients with potential ACS. METHODS: We performed a prospective cohort study of ED patients with chest pain who received an electrocardiogram for potential ACS. Data included demographics, medical history, stress test history, and TIMI risk score. Patients were followed in-house; 30-day telephone interviews were performed for follow-up. Main outcomes were ED disposition (admit/discharge) and a composite of 30-day death, acute myocardial infarction, and revascularization stratified on the basis of prior stress testing known at the time of presentation. Standard statistical techniques were used with 95% confidence intervals (CI). RESULTS: There were 1853 patients enrolled and 97% had follow-up. Patients had a mean age of 53 +/- 14 years; 60% were women, 67% were black. There were 1491 (79%) patients without a prior stress test, 291 (16%) had a normal prior stress test result, and 89 (5%) had an abnormal prior stress test result. Admission rates were 92% (95% CI, 87%-98%) for patients with a prior abnormal stress test, 73% (95% CI, 67%-78%) for patients with a normal prior stress test, and 70% (95% CI, 67%-72%) for patients without a prior stress test. Adverse outcomes were the highest among patients with prior abnormal stress test but did not differ significantly between patients with no prior stress test and patients with prior normal stress test (10.1% [95% CI, 3.6-16.7%] vs 5.2% [95% CI, 4.1-6.4%] vs 4.8% [95% CI, 2.4-7.3%]). CONCLUSION: Patients without prior stress tests and patients with prior normal stress tests were admitted for potential ACS at the same rate and had the same 30-day cardiovascular event rates. This suggests that prior stress testing does not affect subsequent disposition decisions. Perhaps cardiac catheterization or computed tomography coronary angiograms would have more of an impact on subsequent visits, making them potentially more cost-effective in the low-risk patient.