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.

Design and implementation of the hospital airway resuscitation trial.

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials-alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.