Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial.

Importance: In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness. Objective: To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. Design, Setting, and Participants: A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018. Interventions: Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474). Main Outcomes and Measures: Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. Results: Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). Conclusions and Relevance: In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02213380.

Supporting adherence for people starting a new medication for a long-term condition through community pharmacies: a pragmatic randomised controlled trial of the New Medicine Service.

OBJECTIVE: To examine the effectiveness of the New Medicine Service (NMS), a national community pharmacy service to support medicines-taking in people starting a new medicine for a long-term condition, compared with normal practice. METHODS: Pragmatic patient-level parallel randomised controlled trial, in 46 community pharmacies in England. Patients 1:1 block randomisation stratified by drug/disease group within each pharmacy. 504 participants (NMS: 251) aged 14 years and over, identified in the pharmacy on presentation of a prescription for asthma/chronic obstructive pulmonary disease, hypertension, type 2 diabetes or an anticoagulant/antiplatelet agent. NMS intervention: One consultation 7-14 days after presentation of prescription followed by another 14-21 days thereafter to identify problems with treatment and provide support if needed. Controls received normal practice. Adherence, defined as missing no doses without the advice of a medical professional in the previous 7 days, was assessed through patient self-report at 10 weeks. Intention-to-treat analysis was employed, with outcome adjusted for recruiting pharmacy, NMS disease category, age, sex and medication count. Cost to the National Health Service (NHS) was collected. RESULTS: At 10 weeks, 53 patients had withdrawn and 443 (85%) patients were contacted successfully by telephone. In the unadjusted analysis of 378 patients still taking the initial medicine, 61% (95% CI 54% to 67%) and 71% (95% CI 64% to 77%) patients were adherent in the normal practice and NMS arms, respectively (p=0.04 for difference). In the adjusted intention-to-treat analysis, the OR for increased adherence was 1.67 (95% CI 1.06 to 2.62; p=0.027) in favour of the NMS arm. There was a general trend to reduced NHS costs, albeit, statistically non-significant, for the NMS intervention: saving £21 (95% CI -£59 to £100, p=0.128) per patient. CONCLUSIONS: The NMS significantly increased the proportion of patients adhering to their new medicine by about 10%, compared with normal practice. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov trial reference number NCT01635361 (http://clinicaltrials.gov/ct2/show/NCT01635361). Current Controlled trials: trial reference number ISRCTN 23560818 (http://www.controlled-trials.com/ISRCTN23560818/; DOI 10.1186/ISRCTN23560818). UK Clinical Research Network (UKCRN) study 12494 (http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12494).

Is admission blood glucose concentration a more powerful predictor of mortality after myocardial infarction than diabetes diagnosis? A retrospective cohort study.

OBJECTIVE: To explore the relative association of admission blood glucose levels and antecedent diabetes on early and long-term survival in a contemporary UK population of patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). DESIGN: Retrospective cohort study based on the Myocardial Ischaemia National Audit Project dataset. SETTING: Tertiary care centre. PARTICIPANTS: 4111 (20.3% known diabetes) consecutive patients admitted with acute myocardial infarction (58.3% STEMI) between October 2002 and September 2008. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause mortality at 30 days and 1 year. The relative association of admission blood glucose and of antecedent diabetes with mortality was assessed using multivariate Cox regression analysis. Furthermore, we compared these relationships in patients with STEMI to those with NSTEMI. RESULTS: By 30 days and 1 year, 409 (9.9%) and 677 (16.5%) of patients died. After adjusting for covariates, diabetes did not show independent association with mortality at any time point, in the entire cohort (HR 30 days 0.93 (95% CI 0.63 to 1.38); 1 year 1.00 (0.77 to 1.30)) or in subgroups of STEMI (HR 30 days 1.03 (0.65 to 1.64); 1 year 1.08 (0.77 to 1.51)) and NSTEMI (HR 30 days 0.62 (0.26 to 1.50); 1 year 0.87 (0.56 to 1.36)). In contrast, after adjusting for covariates, admission glucose showed robust and independent association with mortality in the entire cohort (HR: 30 days 1.07 (1.04 to 1.10); 1 year 1.05 (1.03 to 1.08)), and in the subgroup of STEMI (30 days 1.07 (1.03 to 1.10); 1 year 1.07 (1.04 to 1.10)), and NSTEMI (HR 30 days 1.07 (1.00 to 1.14); 1 year 1.02 (0.97 to 1.06)). CONCLUSIONS: Admission glucose is strongly associated with mortality in all presentations of acute myocardial infarction (AMI), irrespective of established diabetes diagnosis. The increased risk is maintained up to 1 year. Future studies are required to assess the impact of active management of elevated blood glucose in improving mortality in individuals admitted with AMI.