Absolute Risk Difference Research Articles

Comparison Of 3-6 Month Versus 12 Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

Background: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) using third-generation drug-eluting stents (DES) with ultrathin struts and advanced polymer technology. We investigated whether 3-6 month DAPT was non-inferior to 12 month one after implantation of DES with ultrathin struts and advanced polymer technology. Methods: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing PCI using the Orsiro biodegradable-polymer sirolimus-eluting stents (SES) or the Coroflex ISAR polymer-free SES. Patients with ST-segment elevation myocardial infarction were excluded. Patients were randomized to receive either 3-6 month or 12 month DAPT after PCI. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event (NACE), a composite of cardiac death, target vessel myocardial infarction (TVMI), clinically driven target lesion revascularization (CD-TLR), stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure (TLF), a composite of cardiac death, TVMI, CD-TLR, and major bleeding. Results: A total of 2,013 patients (mean age 65.7±10.5, 1,487 male [73.9%], 1,110 [55.1%] presented with acute coronary syndrome) were randomized to 3-6 month DAPT (n=1,002) or 12 month DAPT (n=1,011). The primary outcome occurred in 37 (3.7%) patients in the 3-6 month DAPT group and 41 (4.1%) in the 12 month DAPT group. The non-inferiority of the 3-6 month DAPT group to the 12 month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% confidence interval (CI), -∞% to 1.1%; P<0.001 for non-inferiority]). There were no significant differences in TLF (hazard ratio [HR] 0.98, 95% CI 0.56-1.71, P=0.94) or major bleeding (HR 0.82, 95% CI 0.41-1.61, P=0.56) between the two groups. Across various subgroups, the treatment effect of 3-6 month DAPT was consistent for NACE. Conclusions: Among patients undergoing PCI using third-generation DES, 3-6 month DAPT was non-inferior to 12 month DAPT for NACE. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3-6 month DAPT.

Effects of 12 mg vs. 6 mg dexamethasone on thromboembolism and bleeding in patients with critical COVID-19 - a post hoc analysis of the randomized, blinded COVID STEROID 2 trial

BackgroundThromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19.MethodsUsing additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care.ResultsWe included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of − 0.5% (95% CI − 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes.ConclusionsAmong patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.

Effect of Prosthesis-Patient Mismatch on Long-Term Clinical Outcomes After Bioprosthetic Aortic Valve Replacement

BackgroundProsthesis-patient mismatch (PPM) is common following surgical aortic valve replacement (SAVR). ObjectivesThe purpose of this study was to quantify the impact of PPM on all-cause mortality, heart failure hospitalization, and reintervention following bioprosthetic SAVR. MethodsThis observational nationwide cohort study from SWEDEHEART (Swedish Web system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies) and other national registers included all patients who underwent primary bioprosthetic SAVR in Sweden from 2003 to 2018. PPM was defined according to the Valve Academic Research Consortium 3 criteria. Outcomes were all-cause mortality, heart failure hospitalization, and aortic valve reintervention. Regression standardization was used to account for intergroup differences and to estimate cumulative incidence differences. ResultsWe included 16,423 patients (no PPM: 7,377 [45%]; moderate PPM: 8,502 [52%]; and severe PPM: 544 [3%]). After regression standardization, the cumulative incidence of all-cause mortality at 10 years was 43% (95% CI: 24%-44%) in the no PPM group compared with 45% (95% CI: 43%-46%) and 48% (95% CI: 44%-51%) in the moderate and severe PPM groups, respectively. The survival difference at 10 years was 4.6% (95% CI: 0.7%-8.5%) and 1.7% (95% CI: 0.1%-3.3%) in no vs severe PPM and no vs moderate PPM, respectively. The difference in heart failure hospitalization at 10 years was 6.0% (95% CI: 2.2%-9.7%) in severe vs no PPM. There was no difference in aortic valve reintervention in patients with or without PPM. ConclusionsIncreasing grades of PPM were associated with long-term mortality, and severe PPM was associated with increased heart failure. Moderate PPM was common, but the clinical significance may be negligible because the absolute risk differences in clinical outcomes were small.

Cirrhosis is independently associated with complications and mortality following operative treatment of acetabular fractures

IntroductionPatients with cirrhosis are at higher risk for morbidity after injury. Acetabular fractures represent a highly morbid injury pattern. Few studies have specifically examined an effect of cirrhosis on risk of complications after acetabular fracture. We hypothesized that cirrhosis is independently associated with increased risk of inpatient complications following operative treatment of acetabular fractures. MethodsAdults patients with acetabular fracture who underwent operative treatment were identified from Trauma Quality Improvement Program data from 2015 to 2019. Patients with and without cirrhosis were matched on a propensity score predicting cirrhotic status and inpatient complications based on patient, injury, and treatment characteristics. The primary outcome was overall complication rate. Secondary outcomes included serious adverse event rate, overall infection rate, and mortality. ResultsAfter propensity score matching, 137 cirrhosis+ and 274 cirrhosis- remained. No significant differences existed in observed characteristics after matching. Compared to cirrhosis- patients, cirrhosis+ patients experienced 43.4% (83.9 vs 40.5%, p < 0.001) greater absolute risk difference of any inpatient complication, 29.9% (51.8 vs 21.9%, p < 0.001) greater absolute risk difference of serious adverse events, 28.5% (41.6 vs 13.1%, p < 0.001) greater absolute risk difference of any infection, and 2.9% (2.9% vs 0.0%, p = 0.02) greater absolute risk difference of inpatient mortality. ConclusionCirrhosis is associated with higher rates of inpatient complications, serious adverse events, infection, and mortality among patients undergoing operative repair of acetabular fracture. Level of EvidencePrognostic Level III.

Adjuvant immunotherapy in renal cell carcinoma: A living systematic review and network meta-analysis (NMA).

694 Background: The treatment landscape of localized renal cell carcinoma (RCC) is rapidly evolving. Recent trials have demonstrated contrasting efficacy with adjuvant immunotherapy. Therefore, we sought to assess the mixed treatment comparisons among different adjuvant treatment options using updated data from trials and quantified the absolute effect with these treatments stratified by risk categories. Methods: This living network meta-analysis was conducted using the living interactive evidence (LIvE) synthesis framework. We used stratified baseline risks of disease progression from observational data and at 5, 10, 15 years from the Leibovich risk stratification system (based on risk scores ranging from 0 to ≥15). Corresponding intervention risks were then approximated using relative effect estimates (from NMA) and baseline risks. The difference between CIRs and baseline risks were calculated to present absolute risk differences in each risk category. Results: This NMA included eight RCTs with 8480 participants and seven unique treatment options. Pembrolizumab (pembro; rank 1) was associated with improved disease-free survival (DFS) when compared to atezolizumab (atezo; rank 6; hazard ratio: 0.68; 0.49;0.93), and nivolumab-ipilimumab (nivoipi; rank 5; 0.68; 0.48-0.97). However, no statistically significant difference was observed between pembro and atezo for overall survival (0.53; 0.28-1.01). Survival data for nivoIpi was not reported. No new statistically significant differences were observed since last update. The absolute benefit of atezo and nivoipi was minimal with higher T and N patients (Table). The results were similar with increasing Leibovich risk scores. Conclusions: Current evidence favors the use of a risk adapted approach when offering adjuvant immunotherapy. Adjuvant pembrolizumab remains a preferred treatment in patients with RCC who underwent nephrectomy. [Table: see text]

Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States.

As Hepatitis C virus infection (HCV+) rates in kidney donors and transplant recipients rise, direct-acting antivirals (DAA) may affect outcomes. To analyze the effects of HCV+ in donors, recipients, or both, on deceased-donor (DD) kidney transplantation (KT) outcomes, and the impact of DAAs on those effects. The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+ status. We performed patient survival (PS) and death-censored graft survival (DCGS) pairwise comparisons after propensity score matching to assess the effects of HCV+ in donors and/or recipients, stratifying our study by DAA era to evaluate potential effect modification. Pre-DAA, for HCV+ recipients, receiving an HCV+ kidney was associated with 1.28-fold higher mortality (HR 1.151.281.42) and 1.22-fold higher death-censored graft failure (HR 1.081.221.39) compared to receiving an HCV- kidney and the absolute risk difference was 3.3% (95%CI: 1.8%-4.7%) for PS and 3.1% (95%CI: 1.2%-5%) for DCGS at 3 years. The HCV dual-infection (donor plus recipient) group had worse PS (0.56-fold) and DCGS (0.71-fold) than the dual-uninfected. Donor HCV+ derived worse post-transplant outcomes than recipient HCV+ (PS 0.36-fold, DCGS 0.34-fold). In the DAA era, the risk associated with HCV+ in donors and/or recipients was no longer statistically significant, except for impaired PS in the dual-infected vs dual-uninfected (0.43-fold). Prior to DAA introduction, donor HCV+ negatively influenced kidney transplant outcomes in all recipients, while recipient infection only relatively impaired outcomes for uninfected donors. These adverse effects disappeared with the introduction of DAA.

Severe Maternal Morbidity and Mortality Among Immigrant and Canadian-Born Women Residing Within Low-Income Neighborhoods in Ontario, Canada

Evidence indicates that immigrant women and women residing within low-income neighborhoods experience higher adversity during pregnancy. Little is known about the comparative risk of severe maternal morbidity or mortality (SMM-M) among immigrant vs nonimmigrant women living in low-income areas. To compare the risk of SMM-M between immigrant and nonimmigrant women residing exclusively within low-income neighborhoods in Ontario, Canada. This population-based cohort study used administrative data for Ontario, Canada, from April 1, 2002, to December 31, 2019. Included were all 414 337 hospital-based singleton live births and stillbirths occurring between 20 and 42 weeks' gestation, solely among women residing in an urban neighborhood of the lowest income quintile; all women were receiving universal health care insurance. Statistical analysis was performed from December 2021 to March 2022. Nonrefugee immigrant status vs nonimmigrant status. The primary outcome, SMM-M, was a composite outcome of potentially life-threatening complications or mortality occurring within 42 days of the index birth hospitalization. A secondary outcome was SMM severity, approximated by the number of SMM indicators (0, 1, 2 or ≥3 indicators). Relative risks (RRs), absolute risk differences (ARDs), and odds ratios (ORs) were adjusted for maternal age and parity. The cohort included 148 085 births to immigrant women (mean [SD] age at index birth, 30.6 [5.2] years) and 266 252 births to nonimmigrant women (mean [SD] age at index birth, 27.9 [5.9] years). Most immigrant women originated from South Asia (52 447 [35.4%]) and the East Asia and Pacific (35 280 [23.8%]) regions. The most frequent SMM indicators were postpartum hemorrhage with red blood cell transfusion, intensive care unit admission, and puerperal sepsis. The rate of SMM-M was lower among immigrant women (2459 of 148 085 [16.6 per 1000 births]) than nonimmigrant women (4563 of 266 252 [17.1 per 1000 births]), equivalent to an adjusted RR of 0.92 (95% CI, 0.88-0.97) and an adjusted ARD of -1.5 per 1000 births (95% CI, -2.3 to -0.7). Comparing immigrant vs nonimmigrant women, the adjusted OR of having 1 SMM indicator was 0.92 (95% CI, 0.87-0.98), the adjusted OR of having 2 indicators was 0.86 (95% CI, 0.76-0.98), and the adjusted OR of having 3 or more indicators was 1.02 (95% CI, 0.87-1.19). This study suggests that, among universally insured women residing in low-income urban areas, immigrant women have a slightly lower associated risk of SMM-M than their nonimmigrant counterparts. Efforts aimed at improving pregnancy care should focus on all women residing in low-income neighborhoods.

Association of cardiopulmonary bypass with acute kidney injury in patients undergoing coronary artery bypass grafting: a retrospective cohort study.

Association of cardiopulmonary bypass with acute kidney injury in patients undergoing coronary artery bypass grafting: a retrospective cohort study.

Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial.

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated the clinical benefit of the combination of ezetimibe-simvastatin compared to placebo-simvastatin following acute coronary syndrome (ACS). This review highlights key findings from this study with particular attention to the practice-changing impact on guidelines for low-density lipoprotein cholesterol (LDL-C) reduction after ACS, especially among high-risk populations. Consistent reductions in LDL-C have been reported with newer lipid-lowering therapies (proprotein convertase subtilisin/kexin type 9 inhibitors, cholesterol ester transfer proteins, bempedoic acid) in combination with statin in high-risk subgroups. Since high-risk subgroups remain a focus of guidelines, exploration of high-risk subgroups can help define the optimal use of new therapies. Ezetimibe reduced the LDL-C by 16.7mg/dL compared to placebo at 1year, resulting in a significant reduction in the primary composite endpoint (absolute risk difference 2.0%; relative risk difference 6.4%, hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). The benefits achieved with ezetimibein both LDL-C reduction and the primary clinical composite across 10 pre-specified high-risk subgroups, including the elderly; women; patients with diabetes, prior coronary artery bypass graft, history of stroke, polyvascular disease, low baseline LDL-C, renal dysfunction, prior heart failure, and an elevated TIMI risk score for secondary prevention, were similar or greater than in the corresponding non-high-risk subgroups. Safety events were similar between ezetimibe and placebo across the high-risk subgroups. These data support the addition of ezetimibe to statin therapy in high-risk patients who require additional therapy to lower the LDL-C post-ACS.

Establishment of an in vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain and Retinal Fibrosis

Background: The addition of an addiction medicine consult service has been shown to improve mortality and decrease hospital costs but its impact on the proportion of patients discharged against medical advice (DAMA) and in-hospital initiation of medication for opioid use disorder (MOUD) has not been examined. Methods: A retrospective before-after cohort study was performed at an urban, academic medical center between January 1, 2015 and November 1, 2019. We included adult patients with infective endocarditis and injection drug use determined by admitting diagnosis ICD-9 or ICD-10 codes or documentation within the history section of electronic health recordEHR. Our institution implemented a formal addiction medicine consult service on July 1, 2018. We determined the proportion of patients DAMA and the proportion of patients started on MOUD among patients in the pre-intervention (i.e. hospitalized before July 1, 2018) and intervention (i.e. hospitalized July 1, 2018 or after) groups. Results: A total of 171 patients among hospitalized patients with injection drug use-associated infective endocarditis were included with 119 patients in the pre-intervention group and 52 patients in the intervention group. There was no statistically significant difference in patients DAMA [19% vs 15%, absolute risk difference 4.6% (95% confidence interval -8.6% to 17.7%)] between the intervention and pre-intervention groups. However, there was an increase in the proportion of inpatient MOUD initiation in the intervention group compared to the pre-intervention group [56% vs 21%, absolute risk difference 35% (95% confidence interval 19% to 50%)]. Conclusions: The initiation of an addiction medicine consult service was associated with a higher proportion of MOUD initiation but there was no statistically significant association with the proportion of patients DAMA.

Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

BackgroundThe effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. ObjectivesThe purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. MethodsWe searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. ResultsIn 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. ConclusionsIn adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300mg of nirmatrelvir plus 100mg of ritonavir every 12h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI-2.94 to 7.49, P=0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD,-0.62; 95% CI-2.29 to 1.05, P=0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P=0.39; serious adverse events, 4.55% vs. 3.788%, P=0.76). Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. National Natural Science Foundation of China (grant number: 82172152, 81873944).

Operative Versus Nonoperative Treatment of Acute Achilles Tendon Rupture: A Propensity Score-Matched Analysis of a Large National Dataset.

No consensus exists regarding the superiority of operative versus nonoperative management for Achilles tendon ruptures, as multiple randomized controlled trials conducted since the advent of early mobilization protocols have found outcomes for these 2 interventions to be more similar than were previously held. To use a large national database to (1) compare reoperation and complication rates between operative and nonoperative treatment of acute Achilles tendon ruptures and (2) evaluate trends in treatment and cost over time. Cohort study; Level of evidence, 3. The MarketScan Commercial Claims and Encounters database was used to identify an unmatched cohort of 31,515 patients who sustained primary Achilles tendon ruptures between 2007 and 2015. Patients were stratified into operative and nonoperative treatment groups, and a propensity score-a matching algorithm-was used to establish a matched cohort of 17,996 patients (n = 8993 per treatment group). Reoperation rates, complications, and aggregate treatment costs were compared between groups with an alpha level of .05. A number needed to harm (NNH) was calculated from the absolute risk difference in complications between cohorts. The operative cohort experienced a significantly larger total number of complications within 30 days of injury (1026 vs 917; P = .0088). The absolute increase in cumulative risk was 1.2% with operative treatment, which resulted in an NNH of 83. Neither 1-year (1.1% [operative] vs 1.3% [nonoperative]; P = .1201) nor 2-year reoperation rates (1.9% [operative] vs 2% [nonoperative]; P = .2810) were significantly different. Operative care was more expensive than nonoperative care at 9 months and 2 years after injury; however, there was no difference in cost between treatments at 5 years. Before matching, the rate of surgical repair for Achilles tendon rupture remained stable, from 69.7% to 71.7% between 2007 and 2015, indicating little change in practice in the United States. Results indicated no differences in reoperation rates between operative and nonoperative management of Achilles tendon ruptures. Operative management was associated with an increased risk of complications and higher initial costs, which dissipated over time. Between 2007 and 2015 the proportion of Achilles tendon ruptures managed operatively remained similar despite increasing evidence that nonoperative management of Achilles tendon rupture may provide equivalent outcomes.

Preoperative Loss of Knee Extension Affects Knee Extension Deficit in Patients After Anterior Cruciate Ligament Reconstruction.

Loss of knee extension (LOE) after anterior cruciate ligament reconstruction (ACLR) is associated with limited knee joint function and increased risk for knee osteoarthritis. Preoperative LOE will affect postoperative LOE for up to 12 months after ACLR. Cohort study; Level of evidence, 2. Included were patients who underwent anatomic ACLR between June 2014 and December 2018. In all patients, the postoperative rehabilitation protocol was the same. A heel height difference (HHD) ≥2 cm between the affected and the contralateral leg was used as a measure of LOE. Based on preoperative HHD, patients were divided into LOE and no-LOE groups. The HHD was reevaluated at 1, 3, 4, 6, 9, and 12 months postoperatively. Proportional hazards analysis was used, with the dependent variable being whether a postoperative HHD <2 cm was achieved; the independent variables being the presence or absence of preoperative LOE; and the adjusted variables being age, sex, time to surgery, and presence of meniscal sutures. A total of 389 patients (208 female, 181 male; median age, 21.0 years) were included in the study. There were 55 patients in the LOE group and 334 patients in the no-LOE group. The incidence of LOE at 12 months after ACLR was 13.8% in the no-LOE group and 38.2% in the LOE group (P < .001), with an absolute risk difference of 24.4%. The hazard ratio for achieving postoperative HHD <2 cm was 2.79 for the LOE group versus the no-LOE group (P < .001). Patients with preoperative LOE were nearly 3 times more likely than those without LOE to have LOE at 12 months after ACLR.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P=0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Prevalence and change in social inequalities in physical activity before and during the COVID-19 pandemic in Sweden

BackgroundPhysical activity is crucial for our wellbeing. Since the COVID-19 pandemic emerged, physical activity behaviour has changed globally, and social inequalities that already exist in physical activity have increased. However, there is limited knowledge of how these inequalities have evolved in Sweden. Thus, the aim of this study was to assess the prevalence of physical activity, and the socioeconomic inequalities in physical activity before and during the COVID-19 pandemic.MethodsThis study analysed data from the national ‘Health on Equal Terms’ survey which was conducted on participants between 16 and 84, through a repeated cross-sectional design in 2018 (pre-pandemic) and 2021 (during the pandemic). The socioeconomic variables included gender, age, education, occupation, income, and place of birth. For both years, the prevalence of low physical activity, the absolute risk differences, the slope index of inequality, and the slope index difference for each of the variables were calculated.ResultsThe level of physical activity increased for the total population studied. However, the social inequalities that existed in 2018 increased over time and across age, education, occupation, income, and place of birth, but not with regard to gender.ConclusionsEven though the Swedish population increased their levels of physical activity during the COVID-19 pandemic, the social inequalities that already existed in physical activity increased. Interventions to increase the level of physical activity among the young, people with low socioeconomic status, and those born outside Sweden are needed to reduce these social inequalities, and to improve the Swedish population’s wellbeing.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. The Netherlands Organization for Health Research and Development.

Duration of untreated illness and clinical correlates in first-episode and drug-naïve patients with major depressive disorder

BackgroundsThe notion that a prolonged duration of untreated illness (DUI) leads to poorer outcomes has contributed to extensive changes in mental health services worldwide. However, most studies on DUI have focused on schizophrenia and related psychosis. This study aimed to assess the possible relationship between DUI and certain clinical correlates in first-episode and drug-naïve patients with major depressive disorder (MDD). MethodsThis cross-sectional study recruited 1718 first-episode and drug-naïve MDD outpatients. All participants were scored on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, and thyroid hormone and metabolic parameters were measured. We used the Structure Clinical Interview for DSM-IV for clinical diagnosis and investigated suicide attempts through face-to-face interviews. ResultsA total of 171 (10%) of MDD patients had co-morbid psychiatric symptoms. Participants who were older, with lower education level, and married were less likely to seek a timely treatment compared to the counterparts. One-month longer untreated duration was associated with 2% to 9% higher odds of being with most of the investigated clinical conditions. For those with the longest DUI, the risk was increased for most of the investigated clinical conditions, with absolute risk differences ranging from 5.19% to 29.48%. ConclusionsThese findings suggest that longer DUI may be negatively associated with clinical correlates in MDD. Further long-term follow-up studies are warranted to confirm these preliminary results.

Appropriateness of the Modality of Revascularization According to the SYNTAX Score II 2020 in the FASTTRACK CABG Study: An Interim Report on Patient Selection

BackgroundPersonalized long term vital prognosis plays a key role in deciding between percutaneous coronary intervention (PCI) and CABG in patients with complex coronary artery disease. The FASTTRACK CABG trial enrolls patients with the sole guidance of coronary computed tomographic angiography (CCTA) and fractional flow reserve CCTA (FFRCT). The feasibility/non-feasibility of this approach is determined by the surgeon request to have access to the invasive coronary angiography. MethodsThis interim analysis, which was requested by the Data and Safety Monitoring Board (DSMB), compared the treatment decision of the “on site” Heart team to the recommended treatment as per the SYNTAX Score II 2020 (SS-2020), which was prospectively assessed by the central core laboratory in the first 57 consecutive patients (half of the planned population) enrolled in this First in Man study. ResultsThe average anatomical SYTAX Score is 35.6 ± 11.5. The SS-2020 predicted 5-year MACE and 10-year all-cause mortality are 14.7 % and 21.6 % following CABG, and 23.0 % and 30.4 % following PCI. Among the enrolled patients the SS-2020 predicts long-term PCI outcomes similar to CABG (absolute risk difference ≤0 % in favor of PCI) in only two patients whilst the remaining 55 patients had a predicted survival benefit with CABG. ConclusionsAccording to the SS-2020, the first 57 patients recruited into the FASTTRACK CABG trial received the appropriate modality of revascularization and the DSMB allowed the investigators to complete the study.

Utilization and Outcomes of Clinically Indicated Invasive Cardiac Care in Veterans with Acute Coronary Syndrome and Chronic Kidney Disease.

Of studies reporting an association of CKD with lower use of invasive cardiac care to treat acute coronary syndrome (ACS), just one accounted for the appropriateness of such care. However, its findings in patients hospitalized nearly 30 years ago may not apply to current practice. In a more recent cohort of 64,695 veterans hospitalized with ACS, CKD was associated with a 32% lower likelihood of receiving invasive care determined to be clinically indicated. Among patients with CKD, not receiving such care was associated with a 1.39-fold higher risk of 6-month mortality. Efforts to elucidate the reasons for this disparity in invasive care in patients with ACS and CKD and implement tailored interventions to enhance its use in this population may offer the potential to improve clinical outcomes. Previous studies have shown that patients with CKD are less likely than those without CKD to receive invasive care to treat acute coronary syndrome (ACS). However, few studies have accounted for whether such care was clinically indicated or assessed whether nonuse of such care was associated with adverse health outcomes. We conducted a retrospective cohort study of US veterans who were hospitalized at Veterans Affairs Medical Centers from January 2013 through December 2017 and received a discharge diagnosis of ACS. We used multivariable logistic regression to investigate the association of CKD with use of invasive care (coronary angiography, with or without revascularization; coronary artery bypass graft surgery; or both) deemed clinically indicated based on Global Registry of Acute Coronary Events 2.0 risk scores that denoted a 6-month predicted all-cause mortality ≥5%. Using propensity scoring and inverse probability weighting, we examined the association of nonuse of clinically indicated invasive care with 6-month all-cause mortality. Among 34,430 patients with a clinical indication for invasive care, the 18,780 patients with CKD were less likely than the 15,650 without CKD to receive such care (adjusted odds ratio, 0.68; 95% confidence interval, 0.65 to 0.72). Among patients with CKD, nonuse of invasive care was associated with higher risk of 6-month all-cause mortality (absolute risk, 21.5% versus 15.5%; absolute risk difference 6.0%; adjusted risk ratio, 1.39; 95% confidence interval, 1.29 to 1.49). Findings were consistent across multiple sensitivity analyses. In contemporary practice, veterans with CKD who experience ACS are less likely than those without CKD to receive clinically indicated invasive cardiac care. Nonuse of such care is associated with increased mortality.