Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review.

OBJECTIVE: To compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. DESIGN: Systematic review of randomised controlled trials (RCTs). DATA SOURCES: Medline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020. STUDY SELECTION AND REVIEW METHODS: RCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from -1.7% to -2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from -1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from -12.8% to -5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty). CONCLUSIONS: The reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD. PROSPERO REGISTRATION NUMBER: CRD42020179087

Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery:An Individual Patient Data Meta-Analysis

IMPORTANCE: Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed.OBJECTIVE: To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery.DATA SOURCES: MEDLINE, EMBASE, and CINAHL from inception to May 2020.STUDY SELECTION: Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020.DATA EXTRACTION AND SYNTHESIS: Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data.MAIN OUTCOMES AND MEASURES: The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD.RESULTS: A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for &gt;85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index &lt;18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for &gt;10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72).CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.</p

Right Heart and Pulmonary Hemodynamic Response to Prolonged Exercise in Middle-Aged Endurance Athletes

Chronic endurance exercise has shown to contribute to disproportionate right ventricular (RV) remodeling in athletes, and prolonged strenuous exercise has been associated with acute changes in RV function post-exercise, which are transient. RV function has been closely coupled to pulmonary arterial (PA) hemodynamics, and PA pressures appear to increase progressively with exercise intensity. There is however a paucity of directly-measured pulmonary hemodynamic data to support this observation. We characterized the PA hemodynamic and RV functional responses to acute, step-incremental (n=16) and sustained steady-state aerobic exercise (n=5) in healthy, middle-aged endurance athletes. All subjects underwent simultaneous right heart catheterization and echocardiography. PA pressures increased after initiation of exercise, then stabilized, without further change during acute and prolonged exercise. Accordingly, indices of RV function did not decline during prolonged exercise, altogether arguing against the notion that sustained elevations in pulmonary pressures may compromise RV systolic performance during prolonged aerobic exercise.M.Sc

Alterations of pulmonary vascular afterload in exercise‐induced pre‐ and post‐capillary pulmonary hypertension

Abstract Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance‐compliance time. In health, afterload stress stabilizes during steady‐state exercise. Our objective was to examine alterations of these exercise‐associated stresses in states of pre‐ and post‐capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady‐state exercise at moderate intensity in patients who exhibited Pre‐capillary (n = 22) and post‐capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR‐HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post‐capillary PH and NOR‐HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre‐capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance‐compliance time at rest (r2 = 0.843) and exercise (r2 = 0.760). Exercise resistance‐compliance time was longer in pre‐capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance‐compliance time was shortest in post‐capillary PH compared to pre‐capillary PH and NOR‐HD and associated with limited increases in exercise diastolic pressure gradient. During steady‐state, modest‐intensity exercise‐specific patterns of pulmonary vascular afterload responses were observed in pre‐ and post‐capillary PH relative to NOR‐HD. Longer resistance‐compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre‐capillary PH, while shorter resistance‐compliance time appeared to limit these increases in post‐capillary PH

Factors Associated with the Magnitude Of acUpuncture treatment effectS (FAMOUS): a meta-epidemiological study of acupuncture randomised controlled trials

Objective To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas.Data source Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019.Study selection The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons.Data analysis The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model.Results 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (&gt;0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2–0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (&lt;0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25).Conclusion Patients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects