Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Women Are Less Likely to Survive AMI Presenting With Out-of-Hospital Cardiac Arrest: A Nationwide Study

ObjectiveTo assess the impact of patient’s sex on outcomes and management of acute myocardial infarction (AMI) patients presenting with out-of-hospital cardiac arrest (OHCA).Patients and MethodsWe conducted a population-based retrospective cohort study in AMI patients admitted with OHCA between 2010 and 2017 from the Myocardial Ischaemia National Audit Project (MINAP) registry. We used multivariable logistic regression models to evaluate the role of sex as a predictor of clinical outcomes and treatment strategy.ResultsOf 16,278 patients, women constituted almost one-quarter of the population (n=3710 [22.7%]). Women were older (median age 69 [IQR, 57-79] years vs 63 [IQR, 54-72] years, P<.001), experienced longer call-to-hospital-arrival time (median, 1.2 hours vs 1.1 hours; P=.008), were less likely to present with shockable rhythm (86.8% vs 91.5%, P<.001), and less likely to receive dual antiplatelet therapy (73.8% vs 78.6%, P<.001), beta blockers (64.7% vs 72.3%, P<.001), angiotensin-converting enzyme inhibitors (49.0% vs 55.3%, P<.001), coronary angiography (73.7% vs 83.3%, P<.001), and percutaneous coronary intervention (37.5% vs. 40.7%, p 0.004). After adjusting for patient characteristics and management, women had significantly higher odds of in-hospital death compared with men (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.5) and lower odds of receiving coronary angiography (OR, 0.67; 95% CI, 0.59 to 0.75) and coronary artery bypass graft (OR, 0.28; 95% CI, 0.19 to 0.40).ConclusionWomen were less likely to survive following OHCA secondary to AMI. Hospital protocols that minimize physician bias and improve women-physician communication are needed to close this gap.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Arthritis Prediction of Advanced Hepatic Fibrosis in HFE Hemochromatosis

ObjectiveTo evaluate whether arthritis predicts the likelihood of advanced hepatic fibrosis in HFE hemochromatosis.Patients and MethodsWe conducted a retrospective, cross-sectional analysis of 112 well-characterized patients with HFE hemochromatosis and liver biopsy–validated fibrosis staging recruited between January 1, 1983, and December 31, 2013. Complete clinical, biochemical, hematologic, and noninvasive serum biochemical indices (aspartate aminotransferase to platelet ratio index [APRI] and fibrosis 4 index [FIB4]) were available. Scheuer fibrosis stages 3 and 4, APRI greater than 0.44, or FIB4 greater than 1.1 were used to define advanced hepatic fibrosis. Comparisons between groups were performed using categorical analysis, unpaired or paired t test.ResultsMale (n=76) and female (n=36) patients were similar in age. Nineteen patients had advanced hepatic fibrosis, and 47 had hemochromatosis arthritis. Arthritis was significantly associated with the presence of advanced hepatic fibrosis as determined by liver biopsy (sensitivity, 84%, [95% CI, 62% to 95%]; negative predictive value, 95% [95% CI, 87% to 99%]; relative risk, 7.4 [95% CI, 2.5 to 23]; P<.001), APRI (sensitivity, 75% [95% CI, 55% to 88%]; negative predictive value, 91% [95% CI, 81% to 96%]; relative risk, 4.5 [95% CI, 2.0 to 10.2]; P<.001), or FIB4 (sensitivity, 61% [95% CI, 41% to 78%]; negative predictive value, 67% [95% CI, 68% to 90%]; relative risk, 2.2 [95% CI, 1.1 to 4.6]; P=.03). Mean cell volume values were significantly higher pretreatment in patients with F3-4 fibrosis (96.7±1.1 fL) compared with F0-2 fibrosis (93.4±0.5 fL; P=.004) and declined following treatment (F3-4, 93.2±0.9 fL, P=.01; F0-2, 91.7±0.6 fL, P=.01).ConclusionAdvanced hepatic fibrosis is strongly associated with arthritis in HFE hemochromatosis. The absence of arthritis predicts a low likelihood of advanced hepatic fibrosis, supporting its use as a clinical marker for advanced hepatic fibrosis in HFE hemochromatosis.     

Outcomes of Patients With Type 2 Myocardial Infarction Complicating Acute Ischemic Stroke

ObjectiveTo study the patient profiles and the prognostic impact of type 2 myocardial infarction (MI) on outcomes of acute ischemic stroke (AIS).MethodsThe National Readmission Database 2018 was queried for patients with primary AIS hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between cohorts were compared.ResultsOf 587,550 AIS hospitalizations included in the study, 4182 (0.71%) had type 2 MI. Patients with type 2 MI were older (73.6 years vs 70.1 years; P<.001) and more likely to be female (52% vs 49.7%; P<.001), and they had a higher prevalence of heart failure (32.6% vs 15.5%; P<.001), atrial fibrillation (38.5% vs 24.2%; P<.001), prior MI (8.8% vs 7.7%; P<.001), valvular heart disease (17% vs 9.8%; P<.001), peripheral vascular disease (12.2% vs 9.2%; P<.001), and chronic kidney disease (24.4% vs 16.7%; P<.001). Compared with patients without type 2 MI, AIS patients with type 2 MI had significantly higher in-hospital mortality (adjusted odds ratio [aOR], 1.96; 95% CI, 1.65 to 2.32), poor functional outcome (aOR, 1.80; 95% CI, 1.62 to 2.00), more hospital costs (adjusted parameter estimate, $5618; 95% CI, $4480 to $6755), higher rate of discharge to a facility (aOR, 1.70; 95% CI, 1.52 to 1.90), increased length of stay (adjusted parameter estimate, 2.22; 95% CI, 1.72 to 2.72), and higher rate of 30-day all-cause readmissions (aOR, 1.38; 95% CI, 1.18 to 1.60).ConclusionType 2 MI in patients hospitalized with AIS is associated with poor prognosis and higher resource utilization.     

Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

Whole Body Vibration Exercise for Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveThis study systematically reviews previous work on the effects of whole body vibration exercise (WBVE) on pain associated with chronic musculoskeletal disorders.Data SourcesSeven electronic databases (PubMed, Embase, CINAHL, Web of Science, Cochrane, Physiotherapy Evidence Database [PEDro], and the China National Knowledge Infrastructure) were searched for articles published between January 1980 and September 2018.Study SelectionRandomized controlled trials involving adults with chronic low back pain (CLBP), osteoarthritis (OA), or fibromyalgia were included. Participants in the WBVE intervention group were compared with those in the nontreatment and non-WBVE control groups.Data ExtractionData were independently extracted using a standardized form. Methodological quality was assessed using PEDro.Data SynthesisSuitable data from 16 studies were pooled for meta-analysis. A random effects model was used to calculate between-groups mean differences at 95% confidence interval (CI). The data were analyzed depending on the duration of the follow-up, common disorders, and different control interventions.ResultsAlleviation of pain was observed at medium term (standardized mean difference [SMD], -0.67; 95% CI, -1.14 to -0.21; I², 80%) and long term (SMD, -0.31; 95% CI, -0.59 to -0.02; I², 0%). Pain was alleviated in osteoarthritis (OA) (SMD, -0.37; 95% CI, -0.64 to -0.10; P<.05; I², 22%) and CLBP (SMD, -0.44; 95% CI, -0.75 to -0.13; P<.05; I², 12%). Long-term WBVE could relieve chronic musculoskeletal pain conditions of OA (SMD, -0.46; 95% CI, -0.80 to -0.13; P<.05; I², 0%). WBVE improved chronic musculoskeletal pain compared with the treatment “X” control (SMD, -0.37; 95% CI, -0.61 to -0.12; P<.05; I², 26%), traditional treatment control (SMD, -1.02; 95% CI, -2.44 to 0.4; P>.05; I², 94%) and no treatment control (SMD, -1; 95% CI, -1.76 to -0.24; P<.05; I², 75%).ConclusionsEvidence suggests positive effects of WBVE on chronic musculoskeletal pain, and long durations of WBVE could be especially beneficial. However, WBVE does not significantly relieve chronic musculoskeletal pain compared with the traditional treatment. Further work is required to identify which parameters of WBVE are ideal for patients with chronic musculoskeletal pain.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

Noninvasive Ventilation in the Management of Respiratory Failure Due to COVID-19 Infection: Experience From a Resource-Limited Setting

ObjectiveTo study the role of noninvasive ventilation (NIV) in Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) related acute respiratory failure (C-ARF).Patients and MethodsPatients with C-ARF managed on NIV were categorized as NIV success or failure (death or intubation). Factors associated with failure were explored using regression analysis and expressed as odds ratio (OR) with 95% CI.ResultsBetween April 1, 2020, and September 15, 2020, a total of 286 patients with a mean ± SD age of 53.1±11.6 years and Acute Physiology and Chronic Health Evaluation II score of 11.1±5.5 were initiated on NIV. Of the 182 patients (63.6%) successfully managed on NIV alone, 118 had moderate or severe acute respiratory distress syndrome. When compared with NIV success, NIV failure was associated with lower admission PaO₂ to fraction of inspired oxygen ratio (P<.001) and higher respiratory rate (P<.001). On penalized logistic regression analysis, NIV failure was associated with higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.12; 95% CI, 1.01 to 1.24), severe acute respiratory distress syndrome (OR, 3.99; 95% CI, 1.24 to 12.9), D-dimer level of 1000 ng/mL DDU (to convert to mg/L, divide by 1000) or greater (OR, 2.60; 95% CI, 1.16 to 5.87), need for inotropes or dialysis (OR, 12.7; 95% CI, 4.3 to 37.7), and nosocomial infections (OR, 13.6; 95% CI, 4.06 to 45.9). Overall mortality was 30.1% (86/286). In patients requiring intubation, time to intubation was longer in nonsurvivors than survivors (median, 5; interquartile range, 3-8 vs 3; interquartile range, 2-3 days; P<.001).ConclusionNoninvasive ventilation can be used successfully in C-ARF. Illness severity and need for non–respiratory organ support predict NIV failure.     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.     

Adults With Tetralogy of Fallot: Early Postoperative Outcomes and Risk Factors for Complications

ObjectiveTo report the early postoperative outcomes in adults with tetralogy of Fallot (TOF) undergoing cardiac surgery and to identify patient factors associated with complications.Patients and MethodsWe performed a single-institution retrospective review of adults with TOF who underwent cardiac surgery from January 8, 2008, through June 21, 2018. Patients’ characteristics, preoperative imaging, surgical interventions, outcomes, and complications were analyzed.ResultsThere were 219 adults with TOF (mean age, 40 years; range, 18-83 years; 88 [40%] female) in the study. Surgical interventions included repair or replacement of the pulmonary valve (n=199 [91%]), tricuspid valve (n=70 [32%]), mitral valve (n=13 [5.9%]), and aortic valve (n=8 [3.7%]). Three patients (1.4%) underwent first-time TOF repair. The 30-day mortality rate was 1.4% (n=3). Early postoperative complications occurred in 66 (30%) and included arrhythmias requiring treatment, dialysis requirement, liver dysfunction, respiratory failure, infection, reoperation, cardiac arrest, mechanical circulatory support, and death. Multivariate analysis found older age at current surgery (odds ratio [OR], 1.04 per year; 95% CI, 1.01 to 1.06; P<.001), longer cardiopulmonary bypass time (OR, 1.01 per minute; 95% CI, 1.01 to 1.02; P<.001), right ventricular systolic dysfunction (OR, 1.31; 95%, CI 1.02 to 1.69; P=.03), diabetes mellitus (OR, 3.50; 95% CI, 1.20 to 10.2; P=.02), and history of initial palliative surgery (OR, 1.99; 95% CI, 1.01 to 3.91; P=.05) as independent predictors of complications.ConclusionSurgical interventions for adult patients with TOF can be performed with low early morbidity and mortality. Clinical characteristics and preoperative testing parameters can predict risk for complications in the postoperative period.     

Depression as a Predictor of Long-term Employment Outcomes Among Individuals With Moderate-to-Severe Traumatic Brain Injury

ObjectiveTo examine the predictive ability of depression when considering long-term employment outcomes for individuals with moderate-to-severe traumatic brain injury (TBI) after controlling for key preinjury and injury-related variables.DesignSecondary data analysis.SettingCommunity follow-up after discharge from an inpatient rehabilitation center.ParticipantsIndividuals between 18 and 60 years old with moderate-to-severe TBI enrolled in the Traumatic Brain Injury Model Systems database.InterventionsNot applicable.Main Outcome MeasuresEmployment status.ResultsThe prevalence of employment at 2 and 5 years post injury was 40.3% and 44.5%, respectively. Individuals identified as depressed at 1 year were more likely to be unemployed at 2 years post injury (odds ratio [OR], 1.77; 95% CI, 1.38-2.27; P<.0001). Similar relations between current depression and future employment were observed from 1- and 2-year depression status predicting 5-year employment (1-year: OR, 1.88; 95% CI, 1.48-2.40; P<.0001: 2-year: OR, 1.72; 95% CI, 1.36-2.17; P<.0001).ConclusionsAfter controlling for baseline predictors variables, the experience of postinjury depression—a modifiable condition—contributes predictive ability to future employment outcomes. Incorporating assessments and/or interventions for depression into postacute rehabilitation programs could promote favorable employment outcomes after TBI.     

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction

ObjectiveTo evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.MethodsA retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.ResultsOf 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD?, 86% in MAC?/MVD+, and 92% in MAC?/MVD?. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10).ConclusionIn a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.     

Efficacy and Safety of High-Frequency Repetitive Transcranial Magnetic Stimulation for Poststroke Depression: A Systematic Review and Meta-analysis

ObjectiveTo summarize and systematically review the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in patients with stroke.Data SourcesSix databases (Wanfang, the China National Knowledge Infrastructure, PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until November 15, 2018.Study SelectionSeventeen randomized controlled trials were included for meta-analysis.Data ExtractionTwo independent reviewers selected potentially relevant studies based on the inclusion criteria, extracted data, and evaluated the methodological quality of the eligible trials using the Physiotherapy Evidence Database.Data SynthesisWe calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. Physiotherapy Evidence Database scores ranged from 7 to 8 points (mean=7.35). The study results indicated that HF-rTMS had significantly positive effects on depression in patients with stroke. The effect sizes of the SMD ranged from small to large (SMD, -1.01; 95% confidence interval [CI], -1.36 to -0.66; P<.001; I², 85%; n=1053), and the effect sizes of the OR were large (response rates, 58.43% vs 33.59%; OR, 3.31; 95% CI, 2.25-4.88; P<.001; I², 0%; n=529; remission rates, 26.59% vs 12.60%; OR, 2.72; 95% CI, 1.69-4.38; P<.001; I², 0%; n=529). In terms of treatment side effects, the HF-rTMS group was more prone to headache than the control group (OR, 3.53; 95% CI, 1.85-8.55; P<.001; I², 0%; n=496).ConclusionsHF-rTMS is an effective intervention for poststroke depression, although treatment safety should be further verified via large sample multicenter trials.     

A Cross-Sectional Study to Investigate the Effects of Perceived Discrimination in the Health Care Setting on Pain and Depressive Symptoms in Wheelchair Users With Spinal Cord Injury

ObjectivesIn a sample of wheelchair users with spinal cord injury (SCI), the objectives were to investigate which participant characteristics are associated with greater perceived discrimination in the health care setting, and how such discrimination relates to health outcomes of pain and depressive symptoms.DesignSurvey, cross-sectional.SettingSpinal Cord Injury Model Systems (SCIMS) Center.ParticipantsFull-time wheelchair users with SCI from 9 SCIMS centers (N=410), with data collected between 2011 and 2016.InterventionsN/A.Main OutcomesA 7-item questionnaire inquiring about perceived discrimination by hospital staff, self-reported pain severity over the past month using a 0-10 Numeric Rating Scale, and depressive symptoms using the 2-question Patient Health Questionnaire screener.ResultsParticipants who were black or from the lowest income group were more likely to report experiencing more discrimination than those who were white or from the highest income group, respectively (incidence rate ratio=2.2-2.6, P<.01). Those who reported more perceived discrimination had greater risk of severe pain compared to no pain (relative risk [RR]=1.11; 95% confidence interval [95% CI], 1.01-1.23; P<.05), mild depressive symptoms (RR=1.09; 95% CI, 1.02-1.17; P<.05), and severe depressive symptoms (RR=1.12; 95% CI, 1.04-1.21; P<.05) compared to no symptoms.ConclusionsWheelchair users with SCI who were from more disadvantaged groups (black, lower income levels) reported experiencing more discrimination in their health care setting. Furthermore, those who reported more discrimination were more likely to report worse mental and physical health outcomes. Attempts to reduce discrimination in health care settings may lead to better outcomes for people with SCI. These observations were correlational and not causal; a prospective analysis is necessary to prove causation. Future investigations should further explore the effect of discrimination on the many facets of living with an SCI.     

Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy

ObjectiveTo study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery.Patients and MethodsWe retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation.ResultsOf these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience.ConclusionMost major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence.     

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center

ObjectiveTo assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center.Patients and MethodsThis is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities.ResultsIn total, 400,998 admissions were included. Total allogeneic transfusions per 1000 admissions decreased from 607 to 405 over the study time frame, corresponding to an absolute risk reduction for transfusion of 6.0% (95% confidence interval [CI]: 3.6%, 8.3%; P<.001) and a 22% (95% CI: 6%, 37%; P=.006) decrease in the rate of transfusions over projected. The risk of transfusion decreased for all blood components except cryoprecipitate. Transfusion reductions were experienced for all major surgery types except liver transplantation, which remained stable over time. Hospital length of stay (multiplicative increase in geometric mean 0.85 [95% CI: 0.81, 0.89]; P<.001) and incident in-hospital adverse events (absolute risk reduction: 1.5% [95% CI: 0.1%, 3.0%]; P=.04) were lower than projected at the end of the study time frame.ConclusionPatient blood management implementation for hospitalized patients in a large academic center was associated with substantial reductions in transfusion utilization and improved clinical outcomes. Broad-scale implementation of PBM in US hospitals is feasible without signal for patient harm.     

Effects of Tai Chi on Lower Limb Proprioception in Adults Aged Over 55: A Systematic Review and Meta-Analysis

ObjectiveTo summarize and critically evaluate the effects of Tai Chi on lower limb proprioception in adults older than 55.Data SourcesSeven databases (Scopus, PubMed, Web of Science, SPORTDiscus, Cochrane Library, Wanfang, CNKI) were searched from inception until April 14, 2018.Study SelectionEleven randomized controlled trials were included for meta-analysis.Data ExtractionTwo independent reviewers screened potentially relevant studies based on the inclusion criteria, extracted data, and assessed methodological quality of the eligible studies using the Physiotherapy Evidence Database (PEDro).Data SynthesisThe pooled effect size (standardized mean difference [SMD]) was calculated while the random-effects model was selected. Physiotherapy Evidence Database scores ranged from 5 to 8 points (mean=6.7). The study results showed that Tai Chi had significantly positive effects on lower limb joint proprioception. Effect sizes were moderate to large, including ankle plantar flexion (SMD=−0.55; 95% confidence interval [95% CI], −0.9 to −0.2; P=.002; I²=0%; n=162), dorsiflexion (SMD=−0.75; 95% CI, −1.11 to −0.39; P<.001; I²=0%; n=162), nondominant or left knee flexion (SMD=−0.71; 95% CI, −1.10 to −0.41; P<.001; I²=25.1%; n=266), dominant or right knee flexion (SMD=−0.82; 95% CI, −1.06 to −0.58; P<.001; I²=33.8%; n=464).ConclusionsThere is moderate to strong evidence that suggests that Tai Chi is an effective intervention to maintain and improve lower limb proprioception in adults older than 55. More robust multicenter studies including oldest-old participants, with longer follow-ups and validated outcome measures, are needed before a definitive conclusion is drawn.     

Decline of Influenza and Respiratory Viruses With COVID-19 Public Health Measures: Alberta,Canada

ObjectiveTo determine the incidence of influenza and noninfluenza respiratory viruses (NIRVs) pre-/post-implementation of public health measures aimed to decrease coronavirus disease 2019 (COVID-19) transmission using population-based surveillance data. We hypothesized that such measures could reduce the burden of respiratory viruses (RVs) transmitting via the same routes.Patients and MethodsAn interrupted time-series analysis of RV surveillance data in Alberta, Canada, from May 2017 to July 2020 was conducted. The burden of influenza and NIRVs before and after intervention initiation at week 11 was compared. The analysis was adjusted for seasonality, overdispersion, and autocorrelation.ResultsDuring the study period, an average of 708 and 4056 weekly respiratory multiplex molecular panels were conducted pre-/post-intervention, respectively. We found significant reductions in test positivity rates in the postintervention period for influenza (-94.3%; 95% CI, -93.8 to 97.4%; P<.001) and all NIRVs (-76.5%; 95% CI, -77.3 to -75.8%; P<.001) in the crude model, and -86.2% (95% CI, -91.5 to -77.4%: P<.001) and -75% (95% CI, -79.7 to -69.3%; P<.001), respectively, in the adjusted models. Subanalyses for individual viruses showed significant decreases in respiratory syncytial virus, human metapneumovirus, enterovirus/rhinovirus, and parainfluenza. For non–severe acute respiratory coronavirus 2 human coronaviruses, the decline was not statistically significant after adjustment (-22.3%; 95% CI, -49.3 to +19%, P=.246).ConclusionThe implementation of COVID-19 public health measures likely resulted in reduced transmission of common RVs. Although drastic lockdowns are unlikely to be required given widespread COVID-19 vaccination, targeted implementation of such measures can lower RV disease burden. Studies to evaluate relative contributions of individual interventions are warranted.