Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban,Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism

ObjectiveTo compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).Patients and MethodsConsecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).ResultsIn the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).ConclusionApixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.Trial RegistrationClinicalTrials.gov identifier: NCT03504007.     

Long-Term Risk of Major Adverse Cardiac Events in Atrial Fibrillation Patients on Direct Oral Anticoagulants

ObjectiveTo determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).Patients and MethodsThis study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.ResultsThe mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.ConclusionDOACs are associated with a lower risk of MACE in patients with AF independently from dosage.     

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.     

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.     

Direct Oral Factor Xa Inhibitors for the Treatment of Acute Cancer-Associated Venous Thromboembolism: A Systematic Review and Network Meta-analysis

ObjectiveTo explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE).Patients and MethodsMEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding.ResultsWe identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I²=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise.ConclusionDirect oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.     

Comorbidities As Risk Factors for Rheumatoid Arthritis and Their Accrual After Diagnosis

ObjectiveTo determine the prevalence of comorbidities in rheumatoid arthritis (RA), discover which comorbidities might predispose to developing RA, and identify which comorbidities are more likely to develop after RA.Patients and MethodsWe performed a case-control study using a single-center biobank, identifying 821 cases of RA (143 incident RA) between January 1, 2009, and February 28, 2018, defined as 2 diagnosis codes plus a disease-modifying antirheumatic drug. We matched each case to 3 controls based on age and sex. Participants self-reported the presence and onset of 74 comorbidities. Logistic regression models adjusted for race, body mass index, education, smoking, and Charlson comorbidity index.ResultsAfter adjustment for confounders and multiple comparisons, 11 comorbidities were associated with RA, including epilepsy (odds ratio [OR], 2.13; P=.009), obstructive sleep apnea (OR, 1.49; P=.001), and pulmonary fibrosis (OR, 4.63; P<.001), but cancer was not. Inflammatory bowel disease (OR, 3.82; P<.001), type 1 diabetes (OR, 3.07; P=.01), and venous thromboembolism (VTE; OR, 1.80; P<.001) occurred more often before RA diagnosis compared with controls. In contrast, myocardial infarction (OR, 3.09; P<.001) and VTE (OR, 1.84; P<.001) occurred more often after RA diagnosis compared with controls. Analyses restricted to incident RA cases and their matched controls mirrored these results.ConclusionInflammatory bowel disease, type 1 diabetes, and VTE might predispose to RA development, whereas cardiovascular disease, VTE, and obstructive sleep apnea can result from RA. These findings have important implications for RA pathogenesis, early detection, and recommended screening.     

Outcomes Following Percutaneous Coronary Intervention in Renal Transplant Recipients: A Binational Collaborative Analysis

ObjectiveTo investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI).Patients and MethodsData from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality.ResultsOf the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events.ConclusionThis large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI.     

Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke

ObjectiveTo evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older.Patients and MethodsThis retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding).ResultsA total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use.ConclusionIn patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.     

Sex Differences in Management and Outcomes Among Patients With High-Risk Pulmonary Embolism: A Nationwide Analysis

ObjectiveTo examine the sex differences in management and outcomes among patients with high-risk acute pulmonary embolism (PE).Patients and MethodsThe Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2018. Differences in use of advanced therapies, in-hospital mortality, and bleeding events were compared between men and women.ResultsA total of 125,901 weighted hospitalizations with high-risk PE were identified during the study period; 46.3% were women (n=58,253). Women were older and had a higher prevalence of several comorbidities and risk factors of PE such as morbid obesity, diabetes mellitus, chronic pulmonary disease, heart failure, and metastatic cancer. Systemic thrombolysis and catheter-directed interventions were more commonly used among women; however, mechanical circulatory support was less frequently used. In-hospital mortality was higher among women in the unadjusted analysis (30.7% vs 27.8%, P<.001) and after propensity score matching (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.08 to 1.25; P<.001), whereas the rates of intracranial hemorrhage and non–intracranial hemorrhage were not different. On multivariate regression analysis, female sex (OR, 1.18; 95% CI, 1.15 to 1.21; P<.001) was independently associated with increased odds of in-hospital mortality.ConclusionIn this contemporary observational cohort of patients admitted with high-risk PE, women had higher rates of in-hospital mortality despite receiving advanced therapies more frequently, whereas the rate of major bleeding events was not different from men. Efforts are needed to minimize the excess mortality observed among women.     

Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis

ObjectiveTo assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials.Patients and MethodsWe performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk.ResultsWe included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I²=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up.ConclusionWe found insufficient evidence to support an increased risk of JAK inhibitor–associated VTE based on currently available data.     

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.     

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.     

Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy

ObjectiveTo evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT).Patients and MethodsThis study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score–matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding.ResultsOf these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04).ConclusionIn China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted.Trial Registrationclinicaltrials.gov Identifier: NCT02306616.     

Changes in Burnout and Satisfaction With Work-Life Integration in Physicians and the General US Working Population Between 2011 and 2020

ObjectiveTo evaluate the prevalence of burnout and satisfaction with work-life integration (WLI) among physicians and US workers in 2020 relative to 2011, 2014, and 2017.MethodsBetween November 20, 2020, and March 23, 2021, we surveyed US physicians and a probability-based sample of the US working population using methods similar to our prior studies. Burnout and WLI were measured using standard tools. Information about specific work-related COVID-19 experiences was collected.ResultsThere were 7510 physicians who participated in the survey. Nonresponder analysis suggested that participants were representative of US physicians. Mean emotional exhaustion and depersonalization scores were lower in 2020 than in 2017, 2014, and 2011 (all P<.001). However, emotional exhaustion and depersonalization scores did not improve in specialties most heavily affected by COVID-19. Overall, 38.2% of physicians reported 1 or more symptoms of burnout in 2020 compared with 43.9% in 2017, 54.4% in 2014, and 45.5% in 2011 (all P<.001). Providing care without adequate personal protective equipment (odds ratio [OR], 1.53; 95% CI, 1.35 to 1.72) and having suffered disruptive economic consequences due to COVID-19 (OR, 1.49; 95% CI, 1.32 to 1.69) were independently associated with risk of burnout. On multivariable analysis, physicians were at increased risk for burnout (OR, 1.41; 95% CI, 1.25 to 1.58) and were less likely to be satisfied with WLI (OR, 0.71; 95% CI, 0.64 to 0.79) than other working US adults.ConclusionBurnout and satisfaction with WLI among US physicians improved between 2017 and 2020. The impact of the COVID-19 pandemic on physicians varies on the basis of professional characteristics and experiences. Physicians remain at increased risk for burnout relative to workers in other fields.     

Indirect Comparison of Glucocorticoid-Sparing Agents for Remission Maintenance in Giant Cell Arteritis: A Network Meta-analysis

ObjectiveTo compare and rank the effect of glucocorticoid-sparing agents in giant cell arteritis (GCA), for which several drugs have been evaluated but with a benefit-risk balance that remains uncertain.MethodsThe MEDLINE and Clinical Trials databases were searched up to November 2021; all randomized controlled trials investigating glucocorticoids in GCA were included. The glucocorticoid regimen was dichotomized into short (≤6 months) or prolonged (>6 months) use. Risk of relapse and safety were estimated using network meta-analysis with frequentist random effects models.ResultsOf the 96 records screened, 8 trials were included (572 patients). The trials compared glucocorticoids and a sparing agent: tocilizumab (2 trials), oral methotrexate (3 trials), infliximab (1 trial), etanercept (1 trial), and adalimumab (1 trial). The pooled prevalence of GCA relapse was 52.6% (95% CI, 38.1 to 66.9). The risk of relapse was significantly lower with tocilizumab compared with methotrexate (relative risk [RR], 0.41; 95% CI, 0.17 to 0.97) and prolonged (RR, 0.41; 95% CI, 0.20 to 0.83) and short (RR, 0.32; 95% CI, 0.16 to 0.66) glucocorticoid use. The risk of relapse was not significantly different with methotrexate compared with short (RR, 0.79; 95% CI, 0.48 to 1.31) and prolonged (RR, 0.95; 95% CI, 0.31 to 2.89) glucocorticoid use. The frequency of serious adverse events and serious infection was comparable between the different drugs. The certainty of the evidence was low to very low.ConclusionThis meta-analysis suggests that tocilizumab may be superior to other sparing agents to prevent GCA relapse, but with a low to very low certainty of evidence, and that safety is comparable to the other drugs.RegistrationThe protocol of the meta-analysis is registered in the international prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/prospero/; registration CRD42020112387).     

Drug Treatment,Postural Control,and Falls: An Observational Cohort Study of 504 Patients With Acute Stroke,the Fall Study of Gothenburg

ObjectiveTo identify whether, and to what extent, treatment with cardiovascular drugs and neurotropic drugs are associated with postural control and falls in patients with acute stroke.DesignObservational cohort study.SettingA stroke unit at a university hospital.ParticipantsA consecutive sample of patients (N=504) with acute stroke.InterventionsNot applicable.Main Outcome MeasuresPostural control was assessed using the modified version of the Postural Assessment Scale for Stroke Patients. Data including baseline characteristics, all drug treatments, and falls were derived from medical records. Univariable and multivariable logistic regression and Cox proportional hazards models were used to analyze the association of drug treatment and baseline characteristics with postural control and with falls.ResultsIn the multivariable logistic regression analysis, factors significantly associated with impaired postural control were treatment with neurotropic drugs (eg, opioids, sedatives, hypnotics, antidepressants) with an odds ratio (OR) of 1.73 (95% confidence interval [CI], 1.01-2.97, P=.046); treatment with opioids (OR 9.23, 95% CI, 1.58-54.00, P=0.014); age (OR 1.09, 95% CI, 1.07-1.12, P<.0001), stroke severity, which had a high National Institutes of Health Stroke Scale-score (OR 1.29, 95% CI, 1.15-1.45, P<.0001), and sedentary life style (OR 4.32, 95% CI, 1.32-14.17, P=.016). No association was found between neurotropic drugs or cardiovascular drugs and falls.ConclusionsTreatment with neurotropic drugs, particularly opioids, in the acute phase after stroke, is associated with impaired postural control. Since impaired postural control is the major cause of falls in patients with acute stroke, these results suggest opioids should be used with caution in these patients.     

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.     

Prevalence and Risk Factors of Adhesive Capsulitis in Asian Breast Cancer Patients Undergoing an Outpatient Community Cancer Rehabilitation Program

ObjectivesTo investigate the prevalence and risk factors for adhesive capsulitis in postoperative breast cancer patients up to 5 years after surgery who were attending an outpatient community cancer rehabilitation program, and to determine whether any significant relationship exists between arm lymphedema and adhesive capsulitis.DesignCross-sectional observational study.SettingNational cancer rehabilitation center.ParticipantsAsian women (N=135) who underwent breast surgery and were referred for an outpatient community cancer rehabilitation program.InterventionsNot applicable.Main Outcome MeasuresPresence of adhesive capsulitis, lymphedema.ResultsThe prevalence of adhesive capsulitis and lymphedema in this population was 22.2% and 33.3%, respectively. A history of mastectomy (odds ratio [OR], 3.93; 95% confidence interval [CI], 1.23-12.63; P=.021), mastectomy with reconstruction (OR, 2.72; 95% CI, 1.27-30.54; P=.024), and lymphedema (OR, 7.92; 95% CI, 2.73-22.95; P<.001) were found to be significantly associated with adhesive capsulitis on multivariate analysis.ConclusionsAdhesive capsulitis and lymphedema are common in breast cancer survivors. The design of cancer rehabilitation programs for breast cancer survivors should include surveillance and management of adhesive capsulitis, especially in the presence of lymphedema.     

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.