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.

A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department.

STUDY OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A Randomized, Double-Dummy, Emergency Department-Based Study of Greater Occipital Nerve Block With Bupivacaine vs Intravenous Metoclopramide for Treatment of Migraine.

BACKGROUND: Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine. OBJECTIVE: We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine. METHODS: This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED. RESULTS: Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%). CONCLUSION: GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED.

Opioid Use During the Six Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

STUDY OBJECTIVE: Despite the frequent use of opioids to treat acute pain, the long-term risks and analgesic benefits of an opioid prescription for an individual emergency department (ED) patient with acute pain are still poorly understood and inadequately quantified. Our objective was to determine the frequency of recurrent or persistent opioid use during the 6 months after the ED visit METHODS: This was a prospective, observational cohort study of opioid-naive patients presenting to 2 EDs for acute pain who were prescribed an opioid at discharge. Patients were followed by telephone 6 months after the ED visit. Additionally, we reviewed the statewide prescription monitoring program database. Outcomes included frequency of recurrent and persistent opioid use and frequency of persistent moderate or severe pain 6 months after the ED visit. Persistent opioid use was defined as filling greater than or equal to 6 prescriptions during the 6-month study period. RESULTS: During 9 months beginning in November 2017, 733 patients were approached for participation. Four hundred eighty-four met inclusion criteria and consented to participate. Four hundred ten patients (85%) provided 6-month telephone data. The prescription monitoring database was reviewed for all 484 patients (100%). Most patients (317/484, 66%; 95% confidence interval 61% to 70%) filled only the initial prescription they received in the ED. One in 5 patients (102/484, 21%; 95% confidence interval 18% to 25%) filled at least 2 prescriptions within the 6-month period. Five patients (1%; 95% confidence interval 0% to 2%) met criteria for persistent opioid use. Of these 5 patients, all but 1 reported moderate or severe pain in the affected body part 6 months later. CONCLUSION: Although 1 in 5 opioid-naive ED patients who received an opioid prescription for acute pain on ED discharge filled at least 2 opioid prescriptions in 6 months, only 1% had persistent opioid use. These patients with persistent opioid use were likely to report moderate or severe pain 6 months after the ED visit.

Predicting the Transition to Chronic Pain 6 Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

BACKGROUND: Acute pain can transition to chronic pain, a potentially debilitating illness. OBJECTIVE: We determined how often acute pain transitions to chronic pain among patients in the emergency department (ED) and whether persistent pain 1 week after the ED visit was associated with chronic pain. METHODS: An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use and use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on > 50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain, while adjusting for demographic and treatment variables. RESULTS: During a 9-month period, we approached 733 patients for participation and enrolled 484; 450 of 484 (93%) provided 1-week outcomes data and 410 of 484 (85%) provided 6-month outcomes data. One week after the ED visit, 348 of 453 (77%; 95% confidence interval [CI] 73-80%) patients reported pain in the affected area. New-onset chronic pain at 6 months was reported by 110 of 408 (27%; 95% CI 23-31%) patients. Presence of pain 1 week after ED visit was associated with chronic pain (odds ratio 3.6; 95% CI 1.6-8.5). CONCLUSIONS: About one-quarter of ED patients with acute pain transition to chronic pain within 6 months. Persistence of pain 1 week after the ED visit can identify patients at risk of transition.

Randomized Controlled Trial of Intravenous Acetaminophen Versus Intravenous Hydromorphone for the Treatment of Acute Pain in the Emergency Department.

STUDY OBJECTIVE: As clinicians look to nonnarcotic analgesics in the emergency department (ED), it is essential to understand the effectiveness and adverse effects of nonopioid medications in comparison with existing opioid treatments. Studies of intravenous acetaminophen for acute pain in the ED demonstrate mixed results and suffer from small sample sizes and methodological limitations. This study compares intravenous hydromorphone with intravenous acetaminophen in adult ED patients presenting with acute pain. METHODS: This was a prospective, randomized, clinical trial comparing 1 g intravenous acetaminophen with 1 mg intravenous hydromorphone for treatment of adults with severe, acute pain in the ED. The primary outcome was between-group difference in change in numeric rating scale from baseline to 60 minutes postadministration of study medication. Secondary outcomes included the difference in proportion of patients in each group who declined additional analgesia at 60 minutes, received additional medication before 60 minutes, and developed nausea, vomiting, or pruritus. RESULTS: Of 220 subjects randomized, 103 patients in each arm had sufficient data for analysis. At 60 minutes, the mean decrease in numeric rating scale pain score was 5.3 in the hydromorphone arm and 3.3 in the acetaminophen arm, a difference of 2.0 (95% confidence interval [CI] 1.2 to 2.7) favoring hydromorphone. A greater proportion of patients in the hydromorphone arm also declined additional analgesia at 60 minutes (65% versus 44%; difference 21%; (95% CI 8% to 35%). There was no difference in the proportion of patients receiving rescue analgesia before 60 minutes. Significantly more subjects in the hydromorphone group developed nausea (19% versus 3%; difference 16%; 95% CI 4% to 28%) and vomiting (14% versus 3%; difference 11%; 95% CI 0% to 23%). CONCLUSION: Although both 1 mg intravenous hydromorphone and 1 g intravenous acetaminophen provided clinically meaningful reductions in pain scores, treatment with hydromorphone provided both clinically and statistically greater analgesia than acetaminophen, at the cost of a higher incidence of nausea and vomiting.

Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis.

OBJECTIVE: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration. METHODS: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration. RESULTS: 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups. CONCLUSIONS: While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.

Comparative Effectiveness of Patient-Controlled Analgesia for Treating Acute Pain in the Emergency Department.

STUDY OBJECTIVE: We assess the effectiveness of patient-controlled analgesia in the emergency department (ED). We hypothesized that decline in pain intensity from 30 to 120 minutes after initial intravenous opioid administration is greater in patients receiving morphine by patient-controlled analgesia compared with usual care and would differ by a clinically significant amount. METHOD: This was a pragmatic randomized controlled trial of patient-controlled analgesia and usual care (opioid and dose at physician's discretion) in 4 EDs. Entry criteria included age 18 to 65 years and acute pain requiring intravenous opioids. The primary outcome was decline in numeric rating scale pain score 30 to 120 minutes postbaseline. Secondary outcomes included satisfaction, time to analgesia, adverse events, and patient-controlled analgesia pump-related problems. We used a mixed-effects linear model to compare rate of decline in pain (slope) between groups. A clinically significant difference between groups was defined as a difference in slopes equivalent to 1.3 numeric rating scale units. RESULTS: Six hundred thirty-six patients were enrolled. The rate of decline in pain from 30 to 120 minutes was greater for patients receiving patient-controlled analgesia than usual care (difference=1.0 numeric rating scale unit; 95% confidence interval [CI] 0.6 to 1.5; P<.001) but did not reach the threshold for clinical significance. More patients receiving patient-controlled analgesia were satisfied with pain management (difference=9.3%; 95% CI 3.3% to 15.1%). Median time to initial analgesia was 15 minutes longer for patient-controlled analgesia than usual care (95% CI 11.4 to 18.6 minutes). There were 7 adverse events in the patient-controlled analgesia group and 1 in the usual care group (difference=2.0%; 95% CI 0.04% to 3.9%), and 11 pump-programming errors. CONCLUSION: The findings of this study do not favor patient-controlled analgesia over usual ED care for acute pain management.

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.

Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial.

Importance: The choice of analgesic to treat acute pain in the emergency department (ED) lacks a clear evidence base. The combination of ibuprofen and acetaminophen (paracetamol) may represent a viable nonopioid alternative. Objectives: To compare the efficacy of 4 oral analgesics. Design, Settings, and Participants: Randomized clinical trial conducted at 2 urban EDs in the Bronx, New York, that included 416 patients aged 21 to 64 years with moderate to severe acute extremity pain enrolled from July 2015 to August 2016. Interventions: Participants (104 per each combination analgesic group) received 400 mg of ibuprofen and 1000 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 5 mg of hydrocodone and 300 mg of acetaminophen; or 30 mg of codeine and 300 mg of acetaminophen. Main Outcomes and Measures: The primary outcome was the between-group difference in decline in pain 2 hours after ingestion. Pain intensity was assessed using an 11-point numerical rating scale (NRS), in which 0 indicates no pain and 10 indicates the worst possible pain. The predefined minimum clinically important difference was 1.3 on the NRS. Analysis of variance was used to test the overall between-group difference at P = .05 and 99.2% CIs adjusted for multiple pairwise comparisons. Results: Of 416 patients randomized, 411 were analyzed (mean [SD] age, 37 [12] years; 199 [48%] women; 247 [60%] Latino). The baseline mean NRS pain score was 8.7 (SD, 1.3). At 2 hours, the mean NRS pain score decreased by 4.3 (95% CI, 3.6 to 4.9) in the ibuprofen and acetaminophen group; by 4.4 (95% CI, 3.7 to 5.0) in the oxycodone and acetaminophen group; by 3.5 (95% CI, 2.9 to 4.2) in the hydrocodone and acetaminophen group; and by 3.9 (95% CI, 3.2 to 4.5) in the codeine and acetaminophen group (P = .053). The largest difference in decline in the NRS pain score from baseline to 2 hours was between the oxycodone and acetaminophen group and the hydrocodone and acetaminophen group (0.9; 99.2% CI, -0.1 to 1.8), which was less than the minimum clinically important difference in NRS pain score of 1.3. Adverse events were not assessed. Conclusions and Relevance: For patients presenting to the ED with acute extremity pain, there were no statistically significant or clinically important differences in pain reduction at 2 hours among single-dose treatment with ibuprofen and acetaminophen or with 3 different opioid and acetaminophen combination analgesics. Further research to assess adverse events and other dosing may be warranted. Trial Registration: clinicaltrials.gov Identifier: NCT02455518.

Efficacy of an Acute Pain Titration Protocol Driven by Patient Response to a Simple Query: Do You Want More Pain Medication?

STUDY OBJECTIVE: We assess the efficacy of a simple pain titration protocol of 1-mg increments of intravenous hydromorphone, given at fixed intervals, driven solely by patient response to a yes/no question. METHODS: This was a prospective interventional cohort study of nonelderly adults with acute severe pain defined as requiring intravenous opioids in the judgment of the attending emergency physician. All patients received 1 mg intravenous hydromorphone and 30 minutes later were asked, "Do you want more pain medication?" Patients responding yes received an additional 1 mg of intravenous hydromorphone and were asked the same question 30 minutes after receiving it. Those responding no did not receive additional opioid and were asked the question again 30 minutes later. Each patient was queried 4 times. The primary endpoint was the proportion of patients achieving satisfactory pain control, defined as declining additional pain medication on 1 or more occasions. RESULTS: Of 215 patients enrolled, there were 8 protocol violations, leaving 207 patients with analyzable data; 205 of 207 patients (99%; 95% confidence interval 97% to 100%) achieved satisfactory analgesia at 1 or more points during the study. Nine patients desaturated below 95% on room air, 2 had respiratory rates less than 10 breaths/min, and 2 had pulse rates less than 50 beats/min. No adverse events were associated with amount of hydromorphone received. CONCLUSION: A pain protocol, based on titration of 1 mg intravenous hydromorphone, driven solely by patient response to a simple standardized question repeated at intervals, resulted in achievement of satisfactory analgesia on at least 1 occasion in 99% of patients.

Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial.

STUDY OBJECTIVE: More than 1 million patients present to US emergency departments (EDs) annually seeking care for acute migraine. Parenteral antihistamines have long been used in combination with antidopaminergics such as metoclopramide to treat acute migraine in the ED. High-quality data supporting this practice do not exist. We determine whether administration of diphenhydramine 50 mg intravenously+metoclopramide 10 mg intravenously results in greater rates of sustained headache relief than placebo+metoclopramide 10 mg intravenously. METHODS: This was a randomized, double-blind, clinical trial comparing 2 active treatments for acute migraine in an ED. Eligible patients were adults younger than 65 years presenting with an acute moderate or severe headache meeting International Classification of Headache Disorders-2 migraine criteria. Patients were stratified according to presence or absence of allergic symptoms. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining this level of relief without use of any additional headache medication for 48 hours. Secondary efficacy outcomes included mean improvement on a 0 to 10 verbal scale between baseline and 1 hour, the frequency with which subjects indicated they would want the same medication the next time they present to the ED with migraine, and the ED throughput time. Sample size calculation using a 2-sided α of .05, a ß of .20, and a 15% difference between study arms determined the need for 374 patients. An interim analysis was conducted when data were available for 200 subjects. RESULTS: Four hundred twenty patients were approached for participation. Two hundred eight eligible patients consented to participate and were randomized. At the planned interim analysis, the data and safety monitoring board recommended that the study be halted for futility. Baseline characteristics were comparable between the groups. Fourteen percent (29/208) of the sample reported allergic symptoms. Of patients randomized to diphenhydramine, 40% (40/100) reported sustained relief at 48 hours, as did 37% (38/103) of patients randomized to placebo (95% confidence interval [CI] for difference of 3%: -10% to 16%). One hour after medication administration, patients randomized to diphenhydramine improved by a mean of 5.1 on the 0 to 10 scale versus 4.8 for those randomized to placebo (95% CI for difference of 0.3: -0.6 to 1.1). Eighty-five percent (84/99) of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% (77/102) of those who received placebo (95% CI for difference of 9%: -2% to 20%). Median ED length of stay was 122 minutes (interquartile range 84 to 180 minutes) in the diphenhydramine group and 139 minutes (interquartile range 90 to 235 minutes) in the placebo arm. Rates of adverse effects, including akathisia, were comparable between the groups. CONCLUSION: Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes.

Temperature measurement in the adult emergency department: oral, tympanic membrane and temporal artery temperatures versus rectal temperature.

OBJECTIVE: The objective was to compare agreement between three non-invasive measures of temperature and rectal temperatures and to estimate the sensitivity and specificity of these measures to detect a rectal temperature of 38°C or higher. METHODS: We conducted a study of the diagnostic accuracy of oral, tympanic membrane (TM) and temporal artery (TA) thermometry to measure fever in an urban emergency department (ED). Data were collected from adult patients who received rectal temperature measurement. Bland-Altman analysis was performed; sensitivity, specificity and 95% CIs were calculated. RESULTS: 987 patients were enrolled. 36% of the TM and TA readings differed by 0.5°C or more from rectal temperatures, 50% of oral temperatures. TM measures were most precise-the SD of the difference from rectal was 0.4°C TM, and 0.6°C for oral and TA (p<0.001). The sensitivities of a 38°C cutpoint on oral, TM and TA measures to detect a rectal temperature of 38°C or higher were: 37.0%, 68.3% and 71.1%, respectively (oral vs TM and TA p<0.001). The corresponding specificities were 99.4%, 98.2% and 92.3% (oral, TM and TA) with oral specificity significantly higher than the other two methods (p<0.01). TM and TA cutpoints of 37.5°C provided greater than 90% sensitivity to detect fever with specificity of 90% and 72%, respectively. CONCLUSIONS: None of the non-invasive methods met benchmarks for diagnostic accuracy using the criterion of 38°C to detect rectal temperature of 38°C. A TM cutpoint of 37.5°C provides maximum diagnostic accuracy of the three non-invasive measures.

Age But Not Sex Is Associated With Efficacy and Adverse Events Following Administration of Intravenous Migraine Medication: An Analysis of a Clinical Trial Database.

BACKGROUND: Migraine prevalence is associated with both sex and age. Differences in efficacy of parenteral migraine medication administration based on the sex and age of the patient have not been explored in the published literature. OBJECTIVE: The objective was to determine whether sex and age are associated with short-term headache relief, sustained headache freedom, or adverse medication effects in data collected during 3 emergency department (ED)-based acute migraine comparative efficacy trials. METHODS: Data were combined from 3 studies in which patients who presented to an ED with acute migraine were randomized to one of the following intravenous medication regimens: (1) metoclopramide combined with diphenhydramine; (2) metoclopramide combined with diphenhydramine and dexamethasone; (3) metoclopramide alone; (4) ketorolac; or (5) valproate. In each of these studies, (1) short-term efficacy (patient description of the headache as "mild" or "none" 1 hour after medication administration); (2) sustained efficacy (patient description of the headache as "none" within 2 hours of medication administration and no headache recurrence for 24 hours post ED discharge); and (3) the frequency of any adverse medication effects within 24 hours of medication administration was determined. For each of the medication regimens studied, efficacy and adverse event rates were compared between men vs women and the older vs the younger half of patients. Multivariate logistic regression models were constructed in which sex and age were maintained in the model as well as variables representing each of the medication regimens patients received. RESULTS: A total of 884 patients were included in this analysis (140 men and 744 women). The median age was 35 years. After controlling for age and medication received, female sex was not associated with short-term efficacy (OR 0.98 [95% confidence interval (CI): 0.66, 1.46]), sustained efficacy (OR 0.72 [95%CI: 0.45, 1.15]), or adverse events (OR 1.14 [95%CI: 0.77, 1.71]). Age >36 years, however, was associated with short-term efficacy (OR 0.66 [95%CI: 0.49, 0.88]), sustained efficacy (OR 0.50 [95%CI: 0.34, 0.73]), and adverse events (OR 1.36 [95%CI: 1.02, 1.82]). CONCLUSION: Sex was not associated with response to parenteral acute migraine medication. Age was associated with both efficacy and adverse events.

Comparative Analgesic Efficacy of Oxycodone/Acetaminophen vs Codeine/Acetaminophen for Short-Term Pain Management Following ED Discharge.

OBJECTIVE: To test the hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen following emergency department (ED) discharge. DESIGN: Prospective, randomized, double-blind, trial. SETTING: Adult inner city ED. SUBJECTS: ED patients with acute extremity pain who were discharged home. METHODS: Patients randomized to oxycodone/acetaminophen (5 mg/325 mg) or codeine/acetaminophen (30 mg/300 mg). The primary outcome, obtained via telephone one day after ED discharge, was the between-group difference in improvement in numerical rating scale (NRS) pain scores over a 2-hour period following the most recent ingestion of study drug. Secondary outcomes included proportion of patients with >50% pain reduction, side-effect profile, and patient satisfaction. RESULTS: Two hundred and forty patients were enrolled. Mean baseline NRS scores were 7.9 in both groups. Mean decrease over 2 hours was 4.5 NRS units in the oxycodone/acetaminophen group vs 4.2 NRS units in the codeine/acetaminophen group, for a clinically and statistically nonsignificant difference of 0.2 NRS units (95% CI -0.4-0.9 NRS units). Similarly, 66% vs 61% achieved >50% pain relief for a nonsignificant difference of 5% (95% CI -8% to 17%). Side-effect profile and patient satisfaction were similar. CONCLUSION: Our hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen was rejected. Although pain within each group was reduced by more than half, the between-group difference was not significant. Pending independent validation, these unexpected findings suggest that codeine/acetaminophen, a Schedule III agent, may be a clinically reasonable outpatient opioid alternative to oxycodone/acetaminophen, a more tightly restricted Schedule II agent thought to be more prone to misuse.

Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial.

IMPORTANCE: Low back pain (LBP) is responsible for more than 2.5 million visits to US emergency departments (EDs) annually. These patients are usually treated with nonsteroidal anti-inflammatory drugs, acetaminophen, opioids, or skeletal muscle relaxants, often in combination. OBJECTIVE: To compare functional outcomes and pain at 1 week and 3 months after an ED visit for acute LBP among patients randomized to a 10-day course of (1) naproxen + placebo; (2) naproxen + cyclobenzaprine; or (3) naproxen + oxycodone/acetaminophen. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, 3-group study was conducted at one urban ED in the Bronx, New York City. Patients who presented with nontraumatic, nonradicular LBP of 2 weeks' duration or less were eligible for enrollment upon ED discharge if they had a score greater than 5 on the Roland-Morris Disability Questionnaire (RMDQ). The RMDQ is a 24-item questionnaire commonly used to measure LBP and related functional impairment on which 0 indicates no functional impairment and 24 indicates maximum impairment. Beginning in April 2012, a total of 2588 patients were approached for enrollment. Of the 323 deemed eligible for participation, 107 were randomized to receive placebo and 108 each to cyclobenzaprine and to oxycodone/acetaminophen. Follow-up was completed in December 2014. INTERVENTIONS: All participants were given 20 tablets of naproxen, 500 mg, to be taken twice a day. They were randomized to receive either 60 tablets of placebo; cyclobenzaprine, 5 mg; or oxycodone, 5 mg/acetaminophen, 325 mg. Participants were instructed to take 1 or 2 of these tablets every 8 hours, as needed for LBP. They also received a standardized 10-minute LBP educational session prior to discharge. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement in RMDQ between ED discharge and 1 week later. RESULTS: Demographic characteristics were comparable among the 3 groups. At baseline, median RMDQ score in the placebo group was 20 (interquartile range [IQR],17-21), in the cyclobenzaprine group 19 (IQR,17-21), and in the oxycodone/acetaminophen group 20 (IQR,17-22). At 1-week follow-up, the mean RMDQ improvement was 9.8 in the placebo group, 10.1 in the cyclobenzaprine group, and 11.1 in the oxycodone/acetaminophen group. Between-group difference in mean RMDQ improvement for cyclobenzaprine vs placebo was 0.3 (98.3% CI, -2.6 to 3.2; P = .77), for oxycodone/acetaminophen vs placebo, 1.3 (98.3% CI, -1.5 to 4.1; P = .28), and for oxycodone/acetaminophen vs cyclobenzaprine, 0.9 (98.3% CI, -2.1 to 3.9; P = .45). CONCLUSIONS AND RELEVANCE: Among patients with acute, nontraumatic, nonradicular LBP presenting to the ED, adding cyclobenzaprine or oxycodone/acetaminophen to naproxen alone did not improve functional outcomes or pain at 1-week follow-up. These findings do not support use of these additional medications in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01587274.

Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the "1+1" hydromorphone titration protocol in treatment of acute, severe pain in the first hour of emergency department presentation.

STUDY OBJECTIVE: We compare a high initial dose of 2 mg intravenous hydromorphone against titration of 1 mg intravenous hydromorphone followed by an optional second dose. METHODS: Patients aged 21 to 64 years with severe pain were randomly allocated to 2 mg intravenous hydromorphone in a single bolus or the "1+1" hydromorphone titration protocol. 1+1 Patients received 1 mg intravenous hydromorphone followed by a second 1 mg dose 15 minutes later if they answered yes when asked, Do you want more pain medication? The primary outcome was the between-group difference in proportion of patients who declined additional analgesia at 60 minutes. RESULTS: Of the 350 enrolled patients, 334 had sufficient data for analysis. The proportion who declined additional analgesics was 67.5% in the 2 mg bolus arm and 67.3% in the 1+1 titration arm (difference 0.2%; 95% confidence interval -9.7% to 10.2%). The between-group difference in numeric rating scale pain scores was 0.4 numeric rating scale units (95% confidence interval -0.3 to 1.1). The incidence of adverse effects was similar; 42.3% of 1+1 patients achieved satisfactory analgesia at 1 hour with only 1 mg hydromorphone. CONCLUSION: A hydromorphone 1+1 titration protocol provides similar pain relief to an initial 2 mg bolus dose, with no apparent clinical advantage to the latter. The 1+1 titration protocol had an opioid-sparing effect because 50% less opioid was needed to achieve satisfactory analgesia for 42.3% of patients allocated to this protocol.

A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches.

STUDY OBJECTIVE: We compare metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, with ketorolac 30 mg intravenously in adults with tension-type headache and all nonmigraine, noncluster recurrent headaches. METHODS: In this emergency department (ED)-based randomized, double-blind study, we enrolled adults with nonmigraine, noncluster recurrent headaches. Patients with tension-type headache were a subgroup of special interest. Our primary outcome was a comparison of the improvement in pain score between baseline and 1 hour later, assessed on a 0 to 10 verbal scale. We defined a between-group difference of 2.0 as the minimum clinically significant difference. Secondary endpoints included need for rescue medication in the ED, achieving headache freedom in the ED and sustaining it for 24 hours, and patient's desire to receive the same medication again. RESULTS: We included 120 patients in the analysis. The metoclopramide/diphenhydramine arm improved by a median of 5 (interquartile range 3, 7) scale units, whereas the ketorolac arm improved by a median of 3 (IQR 2, 6) (95% confidence interval [CI] for difference 0 to 3). Metoclopramide+diphenhydramine was superior to ketorolac for all 3 secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95% CI 2 to 6); for sustained headache freedom, 6 (95% CI 3 to 20); and for wish to receive the same medication again, 7 (95% CI 4 to 65). Tension-type headache subgroup results were similar. CONCLUSION: For adults who presented to an ED with tension-type headache or with nonmigraine, noncluster recurrent headache, intravenous metoclopramide+diphenhydramine provided more headache relief than intravenous ketorolac.

One-week and 3-month outcomes after an emergency department visit for undifferentiated musculoskeletal low back pain.

STUDY OBJECTIVE: Nearly 3 million patients present to US emergency departments (EDs) annually with undifferentiated musculoskeletal low back pain. Little is known about short- and longer-term outcomes in this group. We seek to describe the pain and functional outcomes 1 week and 3 months after discharge in a sample of ED patients presenting with undifferentiated musculoskeletal low back pain. METHODS: We used a prospective observational descriptive cohort design, enrolling ED patients with a chief complaint of low back pain classified as musculoskeletal in origin by the ED attending physician. We defined low back pain as pain originating in the posterior back between the tips of the scapulae and upper buttocks and excluded any patient with a traumatic back injury occurring within the previous month. We interviewed patients in the ED and then by telephone follow-up 1 week and 3 months after ED discharge, using a scripted closed-question data collection instrument. Our primary outcome was functional limitation attributable to low back pain assessed with a validated scale. Secondary outcomes included pain and analgesic use during the 24 hours before each follow-up telephone call. RESULTS: During a 9-month period beginning in July 2009, we approached 894 patients, of whom 556 were enrolled. We obtained follow-up on 97% of our sample at 1 week and 92% at 3 months. One week after ED discharge, 70% (95% confidence interval [CI] 66% to 74%) of patients reported back pain-related functional impairment, 59% (95% CI 55% to 63%) reported moderate or severe low back pain, and 69% (95% CI 65% to 73%) reported analgesic use within the previous 24 hours. Three months after ED discharge, 48% (95% CI 44% to 52%) of patients reported functional impairment, 42% (95% CI 38% to 46%) reported moderate or severe pain, and 46% (95% CI 44% to 50%) reported analgesic use within the previous 24 hours. CONCLUSION: There is substantial short- and longer-term morbidity and ongoing analgesic use among patients who present to an ED with undifferentiated musculoskeletal low back pain.