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2 Minute Medicine Rewind
Ultrasound-Guided Regional Anesthesia by Emergency Physicians for Hip Fractures and Delirium
1. An intervention to increase point-of-care ultrasound-guided regional anesthesia (POCUS-GRA) uptake by emergency physicians was safe, effective, and significantly reduced the odds of delirium.
Evidence Rating Level: 1 (Excellent)
Delirium complicates 20-62% of hip fractures, prolonging hospital stay and increasing mortality. Previous studies have shown that regional anesthesia provides better pain management than parenteral opioid analgesics in hip fractures, and is associated with reduced delirium risk. This study sought to train emergency department (ED) physicians in POCUS-GRA and assess whether this intervention reduces the incidence and duration of delirium in patients with hip fractures. This randomized, stepped-wedge cluster design study randomized the order of ED physician training. Patients treated by an ED physician prior to training were assigned to the control group; patients treated after training were assigned to the intervention group. 732 patients were randomly allocated to the intervention (n = 446; median [IQR] age, 81.0 (73.0-88.0) years; 32.7% male) and control (n = 248; median [IQR] age, 82.0 (75.0-88.0) years; 26.2% male) groups. Once trained, ED physicians completed nerve blocks on 236 participants (52.9%) in the intervention group (compared with 6 of 24 participants before the intervention [2.2%], a 51.7% improvement). The failure rate among trained treating physicians was 1 of 237 attempts (0.4%) vs 3 of 9 attempts (33.3%) among untrained treating physicians. No serious complications and one minor complication occurred. Patients in the intervention group had significantly lower odds of delirium compared to those in the control group (odds ratio, 0.72; 95% CI, 0.57-0.93). There was no significant reduction in the duration of delirium (incident rate ratio, 0.92; 95% CI, 0.67-1.25). Overall, POCUS-GRA training was safe and effectively increased nerve block uptake in the ED. These results also suggest POCUS-GRA is effective at reducing delirium risk. Future studies are required to further establish this finding and identify strategies to improve POCUS-GRA uptake.
Ketamine, Etomidate, and Mortality in Emergency Department Intubations
1. Etomidate is associated with significantly higher in-hospital 7- and 28-day mortality compared with ketamine in rapid sequence intubation (RSI) of severely ill patients in the emergency department (ED).
Evidence Rating Level: 2 (Good)
RSI is critical in emergency airway management in critically ill patients. Etomidate and ketamine are favoured induction agents. However, etomidate inhibits adrenal corticosteroid synthesis, while ketamine is associated with peri-intubation hypotension. Recent studies have suggested etomidate may be associated with higher mortality. This target trial emulation of a prospective, multicenter cohort included 1810 patients (median [IQR] age, 64 (50-74) years; 57.9% male) critically ill patients undergoing emergency intubation across 18 Brazilian EDs. 1048 patients (median [IQR] age, 63 (50-73) years; 59.6% male) received etomidate, and 514 patients (median [IQR] age, 64 (50-74) years; 53.3% male) received ketamine. 7-day (RR, 1.19 [95% CI, 1.04-1.35]; P = .009) and 28-day mortality (RR, 1.14 [95% CI, 1.03-1.27]; P = .01) were significantly higher in the etomidate group. There was no significant difference in the probability of first-attempt intubation success (RR, 0.97 [95% CI, 0.92-1.03]; P = .32). Major adverse events (new hemodynamic instability, severe hypoxemia, cardiac arrest) within 30 minutes after intubation occurred in 31.8% (95% CI, 29.3%-34.3%) of patients in the etomidate group and 30.8% (95% CI, 26.5%-35.2%) of patients in the ketamine group. New hemodynamic instability was less frequent in the etomidate group (RR, 0.78 [95% CI, 0.64-0.95]; P = .02). There were no significant differences in the other complications. While etomidate was associated with a lower risk of peri-intubation hemodynamic instability, it significantly increased mortality at 7 and 28 days. Future randomized clinical trials are required to compare the two agents.
1. Premaintenance positron emission tomography (PET)/computed tomography (CT) and bone marrow multiparameter flow cytometry (BM MFC) are associated with better progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab.
Evidence Rating Level: 1 (Excellent)
Previous studies have shown that BM MFC and PET/CT double negativity in patients with multiple myeloma achieved prolonged PFS compared to patients who were not double negative. However, these findings predate the current era of anti-CD38 monoclonal antibodies, which are currently the standard of care. CASSIOPET is the companion study of CASSIOPEIA, where patients with NDMM were randomized to receive daratumumab, a CD38-targeting monoclonal antibody, plus bortezomib/thalidomide/dexamethasone (D-VTd) or bortezomib/thalidomide/dexamethasone (VTd). These patients then received autologous stem cell transplant (ASCT), and those who achieved a partial response underwent observation-only or maintenance therapy with daratumumab monotherapy. CASSIOPEIA patients were eligible for inclusion in CASSIOPET if they had undergone a PET/CT scan within 6 weeks before the first randomization. 225 patients (median [IQR] age, 59 [8] years; 56.4% male) were included. PET negative patients had better PFS (HR, 0.48; 95% confidence interval [CI], 0.25-0.90; P = .019) and a major trend toward better overall survival (HR, 0.37; 95% CI, 0.12-1.07; P = .056). Patients who achieved both PET and MFC negativity had better PFS than those with at least one positive result (HR, 0.39; 95% CI, 0.26-0.60; P < .0001). These studies confirm the prognostic relevance of premaintenance PET and BM MFC in NDMM patients treated with daratumumab. Double negativity may be a criterion to guide maintenance intensity in NDMM.
1. Use of guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF), and sodium–glucose co-transporter 2 inhibitors (SGLT2i) in heart failure with preserved ejection fraction (HFpEF) remains suboptimal.
Evidence Rating Level: 2 (Good)
Despite advances in heart failure (HF) management, use of quadruple GDMT in HFrEF and SGLT2i in HFmrEF and HFpEF is still lacking. OPTIPHARM-HF is an ongoing prospective, observational, nationwide registry of adult patients with HF in Italy. The primary objective of this registry is to assess prescription and adherence to GDMT and explore reasons for its underuse. 3054 patients (mean [SD] age, 69.2 [12.3] years; 24.8% female) were enrolled. 1720 (56.3%) patients were categorized as HFrEF, 625 (20.5%) as HFmrEF, and 709 (23.2%) as HFpEF. In the HFrEF group, 1555 (90.4%), 322 (18.7%), 1055 (61.3%), 1242 (72.2%) and 1191 (69.2%) patients were treated with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARB), angiotensin receptor–neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists (MRA), and SGLT2i, respectively. 55.9%, 33.0%, 49.5%, 100% and 100% of patients, respectively, achieved ≥ 50% of the target dose of beta-blockers, ACEi/ARB, ARNI, MRA and SGLT2i. 46.6% of patients received quadruple therapy, 29.9% triple therapy, 15.2% double therapy, 5.6% single therapy and 2.7% of patients were without any therapy. Patients on quadruple therapy were more likely to be younger and had fewer comorbidities. There were also substantial differences between sites. In the HFmrEF group, 552 (88.3%) patients were on beta-blockers, 215 (34.4%) patients were on ACEi/ARB, 306 (49.0%) patients were on ARNI (a total of 521 [83%] on ACEi/ARB/ARNI), 392 (62.7%) were on MRA, and 371 (59.4%) were on SGLT2i. In the HFpEF group, 39% of patients were on SGLT2i. These results highlight suboptimal use and dosing of GDMT across the HF spectrum. Future studies are needed to explore the reasons for these findings and pursue interventions to increase GDMT and enhance HF care.
1. Tofacitinib significantly improves patient-reported outcomes compared to placebo in the management of juvenile idiopathic arthritis (JIA).
Evidence Rating Level: 2 (Good)
Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of JIA. Apart from clinical and biochemical markers, patient-reported outcomes (PRO; e.g. physical function, physical and psychological well-being, and pain levels) are key determinants of efficacy. This is a post-hoc analysis of a phase 3, 44-week, randomized, double-blind, placebo-controlled trial. In the open-label run-in phase (part 1, 18 weeks), patients received tofacitinib. During the double-blind phase (part 2, 26 weeks), patients were randomized to continue tofacitinib or switch to placebo for up to an additional 26 weeks. PRO was assessed with the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ). 225 patients (median [IQR] age, 13.0 [9.0-15.0] years; 75.1% female) were enrolled in part 1, 173 of which were randomized in part 2. At week 18, 48.0% of patients achieved minimal clinically important differences (MCID) in CHAQ-DI (score reduction of ≥0.188). The proportion of patients with no disability (CHAQ-disability index = 0) increased from 12.9% (SE 2.2) at baseline to 28.0% (SE 3.0) at week 18. The proportion of patients achieving minimal arthritis pain (CHAQ-Discomfort Index score of ≤0.35) increased from 4.4% (SE 1.4) at baseline to 15.6% (SE 2.4) at week 18. In part 2, a higher proportion of patients receiving tofacitinib achieved no disability compared with patients receiving placebo (38.6% vs. 23.5%; P < 0.05). A higher proportion of patients achieved minimal arthritis pain in the tofacitinib group than in the placebo group (26.1% vs. 11.8%; P < 0.05). Although the efficacy of tofacitinib versus placebo in the treatment of JIA has previously been shown, these results capture aspects of disease that may not be captured by clinical or biochemical markers. Overall, tofacitinib significantly improves patient-reported quality of life compared to placebo.
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