Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF). METHODS: We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause-specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA2DS2-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke. RESULTS: We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8-14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3-33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%-12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5-34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13-22.7]; P=0.034). CONCLUSIONS: ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.

Perioperative ischaemic brain injury and plasma neurofilament light: a secondary analysis of two prospective cohort studies.

BACKGROUND: Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage. METHODS: We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged >65 yr and undergoing non-intracranial, non-carotid surgery. RESULTS: Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] log10 pg ml-1) compared with those without (1.86 [1.48-2.21] log10 pg ml-1; P=0.025). Delirium severity scores were higher in those with postoperative brain injury (19 [17-21]) compared with those without (7 [4-12]; P=0.01). CONCLUSION: Although limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.

Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE): A Translational, Integrated, and Transdisciplinary Approach.

BACKGROUND: It has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart. METHODS: The Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke. CONCLUSIONS: PARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Clonidine in patients undergoing noncardiac surgery.

BACKGROUND: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. METHODS: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02). CONCLUSIONS: Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Aspirin in patients undergoing noncardiac surgery.

BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Mineralocorticoid receptor antagonists for heart failure: systematic review and meta-analysis.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We included randomized controlled trials (RCT) of MRAs in adults with HFpEF or HFrEF if they reported data on major adverse cardiac events or drug safety. RESULTS: We identified 15 studies representing 16321 patients. MRAs were associated with a reduced risk of cardiovascular death (RR 0.81 [0.75-0.87], I2 0%), all-cause mortality (RR 0.83 [0.77-0.88], I2 0%), and cardiac hospitalizations (RR 0.80 [0.70-0.92], I2 58.4%). However, an a-priori specified subgroup analysis demonstrated that these benefits were limited to HFrEF (cardiovascular death RR 0.79 [0.73-0.86], I2 0%; all-cause mortality RR 0.81 [0.75-0.87], I2 0%; cardiac hospitalizations RR 0.76 [0.64-0.90], I2 68%), but not HFpEF (all-cause mortality RR 0.92 [0.79-1.08], I2 0%; cardiac hospitalizations RR 0.91 [0.67-1.24], I2 17%). MRAs increased the risk of hyperkalemia (RR 2.03 [1.78-2.31], I2 0%). Nonselective MRAs, but not selective MRAs increased the risk of gynecomastia (RR 7.37 [4.42-12.30], I2 0% vs. RR 0.74 [0.43-1.27], I2 0%). Evidence was of moderate quality for cardiovascular death, all-cause mortality and cardiovascular hospitalizations; and high-quality for hyperkalemia and gynecomastia. CONCLUSIONS: MRAs reduce the risk of adverse cardiac events in HFrEF but not HFpEF. MRA use in HFpEF increases the risk of harm from hyperkalemia and gynecomastia. Selective MRAs are equally effective as nonselective MRAs, without a risk of gynecomastia.

Surgical and Medical Management of Isolated Tricuspid Valve Infective Endocarditis in Intravenous Drug Users.

BACKGROUND: Tricuspid valve (TV) infective endocarditis (IE) is a known complication of intravenous drug use (IVDU). This study assessed long-term outcomes of surgically and medically treated cases of TV IE. METHODS: This was a retrospective cohort study of all cases of native TV IE treated in London, Ontario between 2008 and 2011. Outcomes for medically and surgically managed cases were assessed at two years. Outcomes related to the timing of surgery were also assessed. RESULTS: Thirty-eight patients were included; seven received valve surgery: five repairs, two replacements. All patients had a history of IVDU. Baseline characteristics were equal in both groups. Death at two years was 43% in the surgical group and 26% in the nonsurgical group (p = 0.522). In those who received surgery within 30 days versus after 30 days from admission, death was 33% and 50%, respectively (p = 1.00). No patients received emergent surgery (within seven days of admission). Twenty-nine percent of the surgical group survived disease free versus 52% of the nonsurgical group. Survival with morbidity was mainly related to ongoing IVDU. The highest risk for mortality in both groups was ongoing IVDU. CONCLUSIONS: In IVDU-related TV IE the highest risk for mortality appears to be ongoing IVDU and persistent or recurrent endocarditis.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use prior to major elective surgery and the risk of acute dialysis.

BACKGROUND: Some studies but not others suggest angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery associates with a higher risk of postoperative acute kidney injury (AKI) and death. METHODS: We conducted a large population-based retrospective cohort study of patients aged 66 years or older who received major elective surgery in 118 hospitals in Ontario, Canada from 1995 to 2010 (n = 237,208). We grouped the cohort into ACEi/ARB users (n = 101,494) and non-users (n = 135,714) according to whether the patient filled at least one prescription for an ACEi or ARB (or not) in the 120 days prior to surgery. Our study outcomes were acute kidney injury treated with dialysis (AKI-D) within 14 days of surgery and all-cause mortality within 90 days of surgery. RESULTS: After adjusting for potential confounders, preoperative ACEi/ARB use versus non-use was associated with 17% lower risk of post-operative AKI-D (adjusted relative risk (RR): 0.83; 95% confidence interval (CI): 0.71 to 0.98) and 9% lower risk of all-cause mortality (adjusted RR: 0.91; 95% CI: 0.87 to 0.95). Propensity score matched analyses provided similar results. The association between ACEi/ARB and AKI-D was significantly modified by the presence of preoperative chronic kidney disease (CKD) (P value for interaction < 0.001) with the observed association evident only in patients with CKD (CKD - adjusted RR: 0.62; 95% CI: 0.50 to 0.78 versus No CKD: adjusted RR: 1.00; 95% CI: 0.81 to 1.24). CONCLUSIONS: In this cohort study, preoperative ACEi/ARB use versus non-use was associated with a lower risk of AKI-D, and the association was primarily evident in patients with CKD. Large, multi-centre randomized trials are needed to inform optimal ACEi/ARB use in the peri-operative setting.

A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with ß-thalassemia.

ß-Thalassemia major (ß-TM) patients require life-long blood transfusions, resulting in iron overload with multi-organ morbidity and mortality. Evidence from small randomized controlled trials (RCTs) published to date for deferiprone (DFP) monotherapy or in combination with deferoxamine (DFO) is unclear. We summarized evidence on the efficacy of DFP monotherapy compared to DFO, and DFP-DFO combination therapy compared to DFP or DFO monotherapy in chronically transfused ß-TM. We searched four electronic databases and examined the grey literature. Two authors independently assessed trial quality and extracted data. We calculated the relative risk for dichotomous outcomes and mean difference (MD) for continuous outcomes. We identified 15 RCTs (1003 participants) that met the inclusion criteria. Deferiprone was more efficacious than DFO in improving cardiac ejection fraction [MD 2.88, 95% CI (95% confidence interval) 1.12 to 4.64, p = 0.001) and endocrine dysfunction (MD 0.09, 95% CI 0.08 to 0.10, p < 0.00001). The DFP-DFO combination therapy was more efficacious than DFP or DFO monotherapy in improving cardiac ejection fraction (MD 5.67, 95% CI 1.32 to 10.02, p = 0.008). There was no significant difference in all other outcomes examined. Meta-analysis on changes in myocardial iron content was not possible due to differences in data presentation. The quality of evidence for all outcomes was low. There is currently insufficient evidence to show that DFP is superior to DFO in the treatment of iron overload. The use of DFP must be weighed against the potential side-effects, patient compliance and preference. Large RCTs with clinically relevant outcomes are required.

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES: Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 µmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS: Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01082874.

Applying the lessons of design thinking: a unique programme of care for acutely unwell, community-dwelling COVID-19 patients.

BACKGROUND: The COVID-19 pandemic limited access to primary care and in-person assessments requiring healthcare providers to re-envision care delivery for acutely unwell outpatients. Design thinking methodology has the potential to support the robust evolution of a new clinical model. AIM: To demonstrate how design thinking methodology can rapidly and rigorously create and evolve a safe, timely, equitable and patient-centred programme of care, and to share valuable lessons for effective implementation of design thinking solutions to address complex problems. METHOD: We describe how design thinking methodology was employed to create a new clinical model of care. Using the example of a novel telemedicine programme to support acutely unwell, community-dwelling COVID-19-positive patients called the London Urgent COVID-19 Care Clinic (LUC3), we show how continuous quality outcomes (safety, timeliness, equity and patient-centredness), as well as patient experience survey responses, can drive iterative changes in programme delivery. RESULTS: The inspiration phase identified four key needs for this patient population: monitoring COVID-19 signs and symptoms; self-managing COVID-19 symptoms; managing other comorbidities in the setting of COVID-19; and escalating care as needed. Guided by these needs, a cross-disciplinary stakeholder group was engaged in the ideation and implementation phases to create a unique and comprehensive telemedicine programme (LUC3). During the implementation phase, LUC3 assessed 2202 community-based patients diagnosed with acute COVID-19; the collected quality outcomes and end-user feedback led to evolution of programme delivery. CONCLUSION: Design thinking methodology provided an essential framework and valuable lessons for the development of a safe, equitable, timely and patient-centred telemedicine care programme. The lessons learnt here-the importance of inclusive collaboration, using empathy to guide equity-focused interventions, leveraging continuous metrics to drive iteration and aiming for good-if-not-perfect plans-can serve as a road map for using design thinking for targeted healthcare problems.

Does this patient have obstructive sleep apnea?: The Rational Clinical Examination systematic review.

IMPORTANCE: Obstructive sleep apnea is a common disease, responsible for daytime sleepiness. Prior to referring patients for definitive testing, the likelihood of obstructive sleep apnea should be established in the clinical examination. OBJECTIVE: To systematically review the clinical examination accuracy in diagnosing obstructive sleep apnea. DATA SOURCES: MEDLINE and reference lists from articles were searched from 1966 to June 2013. Titles and abstracts (n = 4449) were reviewed for eligibility and appraised for evidence levels. STUDY SELECTION: For inclusion, studies must have used full, attended nocturnal polysomnography for the reference standard (n = 42). MAIN OUTCOMES AND MEASURES: Community and referral-based prevalence of obstructive sleep apnea; accuracy of symptoms and signs for the diagnosis of obstructive sleep apnea. RESULTS: The prevalence of sleep apnea in community-screened patients is 2% to 14% (sample sizes 360-1741) and 21% to 90% (sample sizes 42-2677) for patients referred for sleep evaluation. The prevalence varies based on the apnea-hypopnea index (AHI) threshold used for the evaluation (≥5 events/h, prevalence 14%; ≥15/h, prevalence 6%) and whether the disease definition requires symptoms in addition to an abnormal AHI (≥5/h with symptoms, prevalence 2%-4%). Among patients referred for sleep evaluation, those with sleep apnea weighed more (summary body mass index, 31.4; 95% CI, 30.5-32.2) than those without sleep apnea (summary BMI, 28.3; 95% CI, 27.6-29.0; P < .001 for the comparison). The most useful observation for identifying patients with obstructive sleep apnea was nocturnal choking or gasping (summary likelihood ratio [LR], 3.3; 95% CI, 2.1-4.6) when the diagnosis was established by AHI ≥10/h). Snoring is common in sleep apnea patients but is not useful for establishing the diagnosis (summary LR, 1.1; 95% CI, 1.0-1.1). Patients with mild snoring and body mass index lower than 26 are unlikely to have moderate or severe obstructive sleep apnea (LR, 0.07; 95% CI, 0.03-0.19 at threshold of AHI ≥15/h). CONCLUSIONS AND RELEVANCE: Nocturnal gasping or choking is the most reliable indicator of obstructive sleep apnea, whereas snoring is not very specific. The clinical examination of patients with suspected obstructive sleep apnea is useful for selecting patients for more definitive testing.

A case of tinea incognito.

Tinea incognito is a dermatophyte infection of the skin that presents atypically because it has previously been treated with imunnosuppresive medication. Herein we present a case of a middle-aged man who was initially clinically diagnosed to have plaque-type psoriasis on his arms. Over the course of two months of topical hydrocortisone and calciptriol treatment as well as phototherapy, the rash worsened. At the time of presentation to hospital the patient had a pruritic, widespread, sloughing, erythematous rash with areas of eschar. A punch biopsy skin confirmed dermatophyte fungal infection of the skin. Fungal culture was positive for Trichophyton Rubrum and the eruption resolved with systemic anti-fungal therapy. Patient specific risk factors for atypical presentation included poor hygiene and hepatatic disease.

NutriSup-PPN: A pilot randomized control trial of oral nutritional supplementation (ONS) and peripheral parenteral nutrition (PPN) in canadian, malnourished, hospitalized patients.

BACKGROUND & AIMS: Hospitalized malnourished patients experience poor outcomes. Our study determined the feasibility of a novel nutritional care pathway which both rapidly identifies and treats malnourished medical inpatients accounting for the obstacles in nutritional optimization. In our interventional arm, we utilize peripheral parental nutrition (PPN) followed by oral nutritional supplementation (ONS) on a composite outcome of 30 day readmission, mortality and continued admission, as well other important clinical and nutritional outcomes. The study was registered under ClinicalTrials.gov Identifier no. NCT02632630. METHODS: NutriSUP-PPN was a 2 × 2 factorial pilot randomized trial. In two large Canadian hospitals, we recruited 100 adult patients >18 years, < 48 h from admission to a general medicine ward who were moderately or severely malnourished. Patients received: 1. PPN for 5 days and then enhanced ONS until 30 days post randomization; 2. PPN for 5 days and then standard ONS until 30 days; 3. Standard care for intravenous (IV) fluid administration for 5 days and then enhanced ONS until 30 days; 4. Standard care for IV fluid administration for 5 days and standard ONS until 30 days. Our primary outcome was a composite of 30 day readmission, continued admission and mortality. RESULTS: There was no significant differences in the composite outcome of 30 day readmission, continued admission or mortality between any interventional group and control. We did however note a trend in the PPN + ONS arm where only 4/22 patients versus 10/24 patients (p = 0.16) in the control (no PPN, no enhanced ONS) experienced an adverse outcome which was largely driven by a reduction of readmission in the ONS + PPN arm We demonstrated feasibility in recruitment, adherence to protocol, and safety. The incidence of sepsis was greater in the PPN arm compared to control (15.5% versus 4.2%) but was not statistically significant. Improvement in nutritional status for interventional arms were not significant compared to control. However, there was a trend of improvement in preventing decline of nutritional status in both the enhanced ONS arm and PPN + enhanced ONS arm. CONCLUSION: There are signals in our data, which suggest that the combination of PPN with ONS may improve both clinical and nutritional outcomes compared to PPN or ONS alone. We posit that a large, multi-center, definitive randomized control trial is now justified to determine if PPN for up to 5 days along with 30 days of ONS, versus standard of care, will improve a composite outcome of death, continued admission, and readmission at 30 days. However, because PPN was associated with a non-statistically significant increase in episodes of sepsis, future studies should ensure that sepsis episodes are well documented and monitored closely by the data safety monitoring board.

Anticoagulation use in perioperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Perioperative atrial fibrillation is associated with an increased risk of stroke, myocardial infarction, and death after noncardiac surgery. Anticoagulation therapy is effective for stroke prevention in nonsurgical atrial fibrillation, but its efficacy and safety in perioperative atrial fibrillation are unknown. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception until January 2022. We included studies comparing anticoagulation versus no anticoagulation use in patients with perioperative atrial fibrillation after noncardiac surgery. Our study outcomes included stroke ± systemic embolism, bleeding, mortality, myocardial infarction, and venous thromboembolism. We pooled studies using fixed-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable-adjusted results. RESULTS: Seven observational studies but no randomised trials were included. Of the 27,822 patients, 29.1% were prescribed therapeutic anticoagulation. Anticoagulation use was associated with a lower risk of stroke ± systemic embolism (RR 0.73; 95% CI, 0.62-0.85; I2 = 81%; 3 studies) but a higher risk of bleeding (RR 1.14; 95% CI, 1.04-1.25; 1 study). There was a lower risk of mortality associated with anticoagulation use (RR 0.45; 95% CI, 0.40-0.51; I2 = 80%; 2 studies). There was no difference in the risk of myocardial infarction (RR 2.19; 95% CI, 0.97-4.96; 1 study). The certainty of the evidence was very low across all outcomes. CONCLUSION: Anticoagulation is associated with a reduced risk of stroke and death but an increased risk of bleeding. The quality of the evidence is very poor. Randomised trials are needed to better determine the effects of anticoagulation use in this population.

Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis.

BACKGROUND: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. METHODS AND RESULTS: We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. CONCLUSIONS: We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.

Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.

CONTEXT: Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days. OBJECTIVE: To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality. DESIGN, SETTING, AND PARTICIPANTS: A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery. MAIN OUTCOME MEASURES: Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death. RESULTS: A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001). CONCLUSION: Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.