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Background While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away. Methods We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among 11 Japanese private companies (n = 1209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis. Results During the 3.5-year period (follow-up rate: 99.9%), 1014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years. Conclusions Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

BACKGROUND Salvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era. OBJECTIVE To characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median follow-up of 5 years. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Variables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation. RESULTS AND LIMITATIONS Factors associated with BF after SRT include PSA DT

The recent Academic Research Consortium for High Bleeding Risk (ARC-HBR) proposal did not consider acute coronary syndrome (ACS), by consensus, a bleeding criterion per se despite being a high bleeding risk (HBR) scenario. We investigated the applicability of the ARC-HBR classification and criteria in ACS patients.Patients with ACS undergoing coronary stenting between 2012 and 2018 at a tertiary hospital were retrospectively classified as being at HBR if they met ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary endpoint was the 1-year cumulative incidence of Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.Among 4412 patients, 29.5% were at HBR. The incidence of bleeding was higher in the HBR group than in the non-HBR group (9.4% vs 1.3%; P.01). The rates of in-hospital periprocedural and postdischarge bleeding were also higher in the HBR group (4.3% vs 0.5% and 5.3% vs 0.9%, respectively; P.01). Bleeding risk gradually increased with increasing ARC-HBR criteria: 1.8%, 5.0%, 9.4%, 16.8%, 25.2%, and 25.9% for 1 isolated minor criterion, ≥ 2 isolated minor criteria, 1 major criterion (isolated or plus 1 minor criterion), 1 major plus ≥ 2 minor criteria, ≥ 2 major criteria (isolated or plus 1 minor criterion), and ≥ 2 major plus ≥ 2 minor criteria, respectively. Sixteen (80%) out of 20 ARC-HBR criteria satisfied the ARC-HBR predefined cutoffs for BARC 3 or 5 bleeding risk.This study supports the use of the ARC-HBR classification and criteria in the ACS setting. The ARC-HBR classification provides an accurate major bleeding risk estimate and it seems suitable for the identification and management of patients at HBR.

BackgroundIn this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.MethodsData were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.ResultsRisk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.ConclusionsThese findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

Background A variety of dermatoses have been reported in the growing number of patients treated with immune-checkpoint inhibitors (ICIs), but the current understanding of cutaneous immune-related adverse events (irAEs) is limited. Objective To determine the cumulative incidence, distribution, and risk factors of cutaneous irAEs after ICI initiation. Methods This was a retrospective cohort study of patients in a national insurance claims database including cancer patients treated with ICIs and matched controls. Results The study included 8637 ICI patients and 8637 matched controls. The overall incidence of cutaneous irAEs was 25.1%, with a median onset time of 113 days. The ICI group had a significantly higher incidence of pruritus, mucositis, erythroderma, maculopapular eruption, vitiligo, lichen planus, bullous pemphigoid, Grover disease, rash, other nonspecific eruptions, and drug eruption or other nonspecific drug reaction. Patients with melanoma and renal cell carcinoma and those receiving combination therapy were at a higher risk of cutaneous irAEs. Limitations Retrospective design without access to patient chart data. Conclusions This study identifies cutaneous irAEs in a real-world clinical setting and highlights patient groups that are particularly at risk. The results can aid dermatologists at the bedside in the diagnosis of cutaneous irAEs and in formulating management recommendations to referring oncologists regarding the continuation of ICI therapy.

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired. ispartof: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY vol:163 issue:3 pages:1166-1175 ispartof: location:United States status: published

Background The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA. Methods We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model. Results Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12). Conclusions CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF.

The ninth edition of lung cancer staging system recommends that specific driver mutations should be considered as prognostic factors in survival models. This study comprehensively investigated the prognostic value of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with resected lung adenocarcinomas according to different clinicopathologic and radiologic characteristics.In total, 1464 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations from November 2008 to March 2015. Age, sex, smoking status, performance status, tumor-node-metastasis stage, radiologic features, and histologic subtypes were collected. Competing risk model was used to estimate the cumulative incidence rate of recurrence. Cox regression multivariable analyses on recurrence-free survival (RFS) and overall survival (OS) were performed.KRAS mutations were more frequent in male subjects (P .001), current/former smokers (P .001), invasive mucinous adenocarcinoma (P .001), and solid tumors (P .001). In general, KRAS-mutated patients had greater cumulative recurrence rate (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.23-3.08; P .001) and worse overall survival (OS; HR, 1.88; 95% CI, 1.23-2.87; P .001) than KRAS wild-type patients. The OS (P .001) of patients harboring KRAS-G12C/V mutations was shorter than that of other KRAS-mutated patients. Cox multivariable analyses demonstrated that KRAS mutations were independently associated with worse RFS (HR, 5.34; 95% CI, 2.53-11.89; P = .001) and OS (HR, 2.63; 95% CI, 1.03-6.76; P = .044) in part-solid lung adenocarcinomas. For stage I patients, Cox multivariable analyses revealed that KRAS mutation was an independent risk factor for RFS (HR, 2.05; 95% CI, 1.19-3.56; P = .010) and OS (HR, 2.38; 95% CI, 1.29-4.40; P = .005).In this study, we revealed that KRAS mutations was an independent prognostic factor in part-solid tumors and in stage I lung adenocarcinomas. These findings may contribute to the ninth edition of lung cancer staging project.

The impact of multiple listing (ML) strategies on lung transplantation is unknown. Retrospective review of United Network for Organ Sharing (UNOS) registry for lung transplantation between May 1, 2005 and March 31, 2017 was performed. Characteristics of single (SL) and ML candidates were compared, and incidence density matching was used to select up to 10 controls for each case. Overall survival was evaluated using Cox regression stratified by matched sets. Nelson-Aalen estimators were used to estimate the cumulative incidence (CI) of transplant, death on the waiting list, and removal from wait-list as competing risks; Gray's test was used to compare wait list outcomes between groups. 23,445 subjects listed for lung transplant, of which 467 (2%) subjects listed at 2+ centers; 206 matched sets. There was no difference in overall survival of matched cases and controls at 1 year (ML 83.7%, SL 90.2%), 3 years (ML 63.9%, SL 68%), and 5 years (ML 51.9%, SL 49.3%) (p=0.24). The CIs of receiving a lung transplant at 2 years for ML and SL were 83.6% and 71%, respectively. Multi-listing increased the probability of receiving a transplant (p0.001) but was not associated with waitlist mortality (p=0.13). There was no difference in post-transplant survival between ML and SL candidates (HR=0.82, p=0.32). ML was associated with a substantial increase in probability of lung transplantation, but there was no difference in overall survival, post-transplant, or wait-list mortality. Our study permits more informed decision-making for patients considering the ML strategy.

Background/purpose: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored. Methods: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test. Results: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p

Background: The long-term effects of occupational injury (OI) on psychiatric diseases are unclear. This study assessed and compared the effects of OI, no injury (control), and non-OI (NOI) on the development of psychiatric diseases. Methods: We used Taiwan’s National Health Insurance Research Database to investigate the incidence of psychiatric disorders in OI, NOI, and control groups. The subjects were aged 20–50 years, actively employed in 2000, and did not have history of injury or psychiatric disorders. All subjects were followed from 2000 and were classified into OI, NOI, and control groups according to occurrence of target injury later on. Individuals in each group were matched by age, sex, insurance premium before the index date, and year of the index date. Psychiatric disease-free days were compared among the groups using survival analysis and Cox regression. Results: We included a total of 12,528 patients for final analysis, with 4,176 in each group. Compared with the control group, the OI group had an increased occurrence of trauma and stress-related disorder, depressive disorders, anxiety disorders, and alcohol and other substance dependence. These increases were similar to those in the NOI group. Elevated cumulative incidence rate of any psychiatric disorders was observed among those with OI or NOI up to 10 years after injury. Conclusion: We confirmed that OI and NOI induced psychiatric disorders. These findings highlight the need for workers’ compensation mechanisms to consider long-term psychological care among injured workers.

Aim The prevalence of atherosclerotic cardiovascular (CV) disease has risen in Japan due to increasing metabolic risk factors, including dyslipidemia. A positive linear correlation between low-density lipoprotein cholesterol (LDL-C) levels, incidence of CV events, and preventive effects of lipid-lowering therapy (LLT) is well established; however, data in Japan are limited. This analysis evaluated current lipid management practices and risk of recurrent CV events in Japanese post-acute coronary syndrome (ACS) patients. Methods EXPLORE-J is a multicenter, 2-year observational study of hospitalized ACS patients in Japan. Results At 2-year follow-up (n=1944, mean age 66 years, 80.3% male), the cumulative incidence of major adverse cardiovascular events (MACE; death associated with myocardial infarction/cerebrovascular accident [CVA] and other CV death, non-fatal ACS, and non-fatal CVA requiring hospitalization during the observation period) was 6.2%; respective incidences of CV death, non-fatal ACS, and CVA were 0.7%, 4.5%, and 1.7%. Statin, intensive statin, and ezetimibe were prescribed for 93.6%, 8.2%, and 3.9% at visit (V)1 (Day[D]1＋14), and 92.3%, 10.5%, and 11.6% of patients at V5 (D730±30 days), respectively. Mean LDL-C was reduced from first post-ACS measurement (121.3 mg/dL) to V5 (79.8 mg/dL). A limited number of patients achieved LDL-C ＜70 mg/dL from V1-V5 (14.4%-34.6%); those with a greater LDL-C reduction by V1 had a lower probability of MACE, indicating the benefits of early LDL-C reduction post ACS. Conclusions Guideline-recommended LDL-C target achievement post ACS in Japan is suboptimal, suggesting the need for LLT intensification. Additional analyses by risk stratification of the study population and the benefits of lipid management are planned.

Background/Purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan–Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p

Prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) with knowledge of explant data is important for guiding post-LT surveillance and treatment. The RETREAT score was recently introduced for this purpose, but has not been validated outside the USA. In a retrospective single-center study of 169 consecutive patients undergoing LT in Gothenburg, through 2000-2017 (mean age 57 years, 80% men), there were 34 HCC recurrences during a median 4.6-year follow-up. The 5-year cumulative incidence of HCC recurrence was 0% with RETREAT scores of 0-1 (18%), 11-22% with scores of 2-4 (58%), and 65% with scores of 5-8 (24%). The C-statistic, as a measure of discrimination for prediction of HCC recurrence was 0.762, 0.664, 0.616, and 0.717, for the RETREAT score, Milan criteria, UCSF criteria, and post-MORAL criteria. The RETREAT score had no significant impact on patient survival after HCC recurrence (HR 1.00, P = 0.97). In conclusion, the RETREAT score provided valid predictions of post-LT HCC recurrence in a European setting, with the ability to discriminate between high, intermediate, and low risk for HCC recurrence in a clinically important way. Prognosis after recurrence did not differ according to the RETREAT score in our study.

Objectives To estimate the diagnosed incidence of non-affective psychotic disorder between the ages of 13 and 19 years in South-Western British Columbia (BC) and to examine variation in risk by sex, family and neighbourhood income, family migration background, parent mental health contact and birth year. Methods Linked individual-level administrative data were used to construct a cohort of individuals born in 1990–1998 and residing in South-Western BC ( n = 193,400). Cases were identified by either one hospitalization or two outpatient physician visits within 2 years with a primary diagnosis of a non-affective psychotic disorder (ICD-10: F20–29, ICD-9: 295, 297, 298). We estimated cumulative incidence, annual cumulative incidence and incidence rate between the ages of 13 and 19 years, and conducted Cox proportional hazards regression to estimate associations between sociodemographic factors and risk over the study period. Results We found that 0.64% of females and 0.88% of males were diagnosed with a non-affective psychotic disorder between the ages of 13 and 19 years, with increasing risk observed over the age range, especially amongst males. Incidence rate over the entire study period was 106 per 100,000 person-years for females and 145 per 100,000 person-years for males. Risk of diagnosis was elevated amongst those in low-income families and neighbourhoods, those with a parent who had a health service contact for a mental disorder, and more recent birth cohorts. Risk was reduced amongst children of immigrants compared to children of non-migrants. Conclusions Findings from this study provide important information for health service planning in South-Western BC. Future work should examine whether variations in diagnosed incidence is driven by differences in health service engagement or reflect genuine differences in risk.

Introduction: To identify factors affecting potency and to predict ideal patient subgroups who will have the highest chance of being potent after robot-assisted laparoscopic prostatectomy (RALP) based on nerve sparing (NS). Materials and Methods: Analysis of 7268 patients who underwent RALP between 2008 and 2018 with a minimum of 12 months of follow-up was performed. The patients were then categorized into four separate neurovascular bundle-sparing groups (NVB 1-4). A Cox regression analysis was used to determine the independent factors predicting potency outcomes. Cumulative incidence functions were used to depict the probability and time to potency between the NS groups stratified by age and preoperative sexual health inventory in men (SHIM). Results: Cox regression analysis of age, preoperative SHIM score, and grades of NS significantly predicted potency outcomes post-RALP. Patients with SHIM score ≥22 had a better chance of potency vs patients with SHIM NVB 3. Conclusions: Preoperative SHIM, age, and NS are the most influential factors for potency recovery following RALP. Patients with good baseline sexual function had similar postoperative potency, irrespective of their grades of partial NS. In patients with decreased baseline SHIM and older age, a higher grade of partial NS resulted in a significantly better potency compared with a lower grade of partial nerve spare.

Background Transvenous permanent pacemaker (PPM) implantation is an available option for Fontan patients with sinus node dysfunction. However, the thrombogenic potential of leads within the Fontan baffle is unknown. Objective The purpose of this study was to compare the clot burden in Fontan patients with a transvenous atrial PPM to those without a PPM and those with an epicardial PPM. Methods This was a retrospective cohort study of all transvenous PPM implantations in Fontan patients followed at our institution (2000–2018). We performed frequency matching on Fontan type and age group. Primary outcome was identification of intracardiac clot, pulmonary embolus, or embolic stroke. Results Of 1920 Fontan patients, 58 patients (median age 23 years; interquartile range [25th–75th percentiles] 14–33) at the time of transvenous PPM implantation and 174 matched subjects formed our cohort. The type of Fontan performed in case subjects was right atrium–pulmonary artery or right atrium–right ventricle conduit (54%), lateral tunnel (43%), and extracardiac (3%). The cumulative incidence of clot was highest in patients with transvenous PPM, followed by patients with epicardial PPM and no PPM (1.2 vs 0.87 vs 0.67 per 100 person-years of follow-up, respectively). In multivariable analysis, anticoagulation and/or antiplatelet therapy were protective against clot and resulted in reduction of clot risk by 3-fold (incidence rate ratio 0.33; 95% confidence interval 0.21–0.53; P Conclusion In a large cohort of Fontan patients matched for age and Fontan type, patients with transvenous PPM had a higher but not statistically significant incidence of clot compared to those with no PPM and epicardial PPM. Patients treated with warfarin/aspirin had lower clot risk.

Background Atrial fibrillation (AF) is the most common arrhythmia observed with concomitant cardiac surgery. Surgical options include a cut-and-sew technique Maze (CAS) and a cryoablation/bipolar technique Maze (CB). There are limited data comparing the long-term outcomes of these 2 techniques. Methods All patients who underwent either CAS or CB Maze between 2011 and 2018 were included in the study. Chi-square test and Fisher’s exact test or Student’s t test were used to compare differences between baseline characteristics. Kaplan-Meier survival curves were generated for each group. Cumulative incidence functions were generated for AF recurrence and Fine-Gray competing-risk regression was used to determine predictors for AF recurrence. Results A total of 482 patients underwent open surgical ablation. Of those, 287 had CAS and 198 had CB. All procedures were concomitant with cardiac surgery. There was similar long-term mortality between the CAS and CB cohorts (22.3% vs 17.4%; log-rank P = .91). There was no difference in pacemaker implantation (11.1% vs 11.3%; P = .813) or long-term freedom from AF recurrence (73.3% vs 78.2%; P = .294). On Fine-Gray competing-risk regression, New York Heart Association functional class IV (hazard ratio [HR], 2.07; P = .03), concomitant aortic valve replacement (HR, 3.02; P = .01), and concomitant CABG + valve (HR, 2.36; P = .02) were significant independent predictors for AF recurrence; Maze type was not a predictor. Conclusions These data indicate no difference between the CAS vs CB with respect to freedom from long-term AF. Both techniques may be appropriate based on surgeon experience and patient characteristics.

BACKGROUND It is unclear whether hepaticojejunostomy with a continuous suture is suitable for patients with a non-dilated bile duct. METHODS Medical records of patients who underwent pancreatoduodenectomy between 2003 and 2013 were retrospectively reviewed, focusing on the incidence of benign anastomotic stenosis and its relationship with suture method (continuous vs interrupted) and common hepatic duct size. RESULTS Among 336 patients, 172 had a non-dilated (

Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients. Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA2DS2-VASc score of ≥2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9–88.3%], 82.6% (95% CI 82.3–82.9%), 77.7% (95% CI 77.3–78.1%), and 72.0% (95% CI 71.5–72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65–74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA2DS2-VASc score ≥2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49–2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29–1.93) compared with being persistent with OACs. Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence., Graphical Abstract

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre.Design: Randomised, double-masked, parallel-group, phase III equivalence study.Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ.Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

As endoscopic approaches become more widely used to treat early-stage esophageal cancer, reliably identifying patients with less-aggressive tumors is paramount. We sought to identify risk factors for recurrence in patients with completely resected T1 esophageal adenocarcinoma.We retrospectively analyzed a single-institutional database for all patients with completely resected pathologic T1 esophageal adenocarcinoma (1996-2016). Risk factors for recurrence were identified using competing-risk regression methods. Risk stratification was performed on the basis of known preoperative clinicopathologic factors; this model's discriminative power for overall survival was evaluated using a Cox proportional hazards model.Of 243 patients, 32 experienced recurrence. At a median follow-up among survivors of 4 years (range, 0.05-19 years), the 5-year cumulative incidence of recurrence was 15%, and median time to recurrence was 2 years (range, 0.26-6.13 years). On univariable analysis, submucosal invasion, N1 disease, poor differentiation, tumor length, lymphovascular invasion, and multicentricity were significantly associated with recurrence. On multivariable analysis, N1 disease (hazard ratio, 2.93; 95% confidence interval, 1.17-7.34; P = .022) and tumor length (hazard ratio, 1.44; 95% confidence interval, 1.12-1.86; P = .004) were independently associated with recurrence. Risk stratification showed that patients without lymphovascular invasion and a with median tumor length of 0.8 cm (range, 0.10-1.70 cm) had a10% risk of recurrence and improved survival.Pathologic T1 tumors have a 5-year cumulative incidence of recurrence of 15%. Nodal involvement and tumor length were independent risk factors for recurrence, whereas tumors2 cm in length without lymphovascular invasion were associated with a low risk of recurrence.

International audience; PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13–16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2–0.9) to 0.5 (95% CI, 0.3–1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8–1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

To determine risk factors associated with concussion among the general collegiate population using a unique data linkage methodology.Student health medical, counseling, and disability access service data were linked with university enrollment data to provide a comprehensive, deidentified dataset of students who sought care at the student health center for concussion from 2016-2020. Using chi-squared tests and logistic regression, characteristics of students with and without concussion were evaluated.During the study period, 506 concussions from 474 students were identified (cumulative incidence rate of 51.7 per 10,000 students). Significant predictors of concussion included: younger age (21 years): odds ratio (OR) = 3.52 (95% confidence intervals [CI], 2.78, 4.50), Greek affiliation: OR = 1.89 (95% CI, 1.56, 2.30), and utilization of counseling and psychological services: OR = 1.92 (95% CI 1.59, 2.32). Of the students with concussion, 47% had at least one other concussion within the preceding year. History of prior hospitalization or medical imaging for head injury increased subsequent concussion risk by 4.5 fold.Linking unique datasets provides a richer understanding of the characteristics and risk factors associated with student concussions than analysis of a single data source. This comprehensive dataset will enable future targeted interventions to prevent and treat college student concussions.

Background Periprosthetic femur fractures (PFFs) that occur distal to a total hip arthroplasty, Vancouver C fractures, are challenging to treat. We aimed to report patient mortality, reoperations, and complications following Vancouver C PFFs in a contemporary cohort all treated with a laterally based locking plate. Methods We retrospectively identified 42 consecutive Vancouver C PFFs between 2004 and 2018. There was a high prevalence of comorbidities, including 9 patients with neurologic conditions, 9 with a history of cancer, 8 diabetics, and 8 using chronic anticoagulation. Mean time from total hip arthroplasty to PFF was 6 years (range 1 month to 25 years). All fractures were treated with a laterally based locking plate. Fixation bypassed the femoral component in 98% of cases and extended as proximal as the lesser trochanter in 18%. Kaplan-Meier survival was used for patient mortality, and a competing risk model was used to analyze survivorship free of reoperation and nonunion. Mean follow-up was 2 years. Results Patient mortality was 5% at 90 days and 31% at 2 years. Cumulative incidence of reoperation was 13% at 2 years. There were 5 reoperations including revision osteosynthesis for nonunion and/or hardware failure (2), debridement and hardware removal for infection (2), and removal of hardware and total knee arthroplasty for post-traumatic arthritis (1). Cumulative incidence of nonunion was 10% at 2 years. Conclusion Patients who sustained a Vancouver C PFFs had a high mortality rate (31%) at 2 years. Moreover, 13% of patients required a reoperation within 2 years, most commonly for infection or nonunion.

Nonagenarians (90-99 years) have experienced the fastest percent growth in primary total knee arthroplasty (TKA) utilization recently. However, there are limited data on the results of the procedure in this population. The goals of this study are to determine the mortality rate, implant survivorship, clinical outcomes, and complications of primary TKAs in nonagenarians.Our institutional total joint registry was used to identify 105 nonagenarians who underwent 119 primary cemented TKAs for osteoarthritis between 1997 and 2017. Mean age was 92 years, with 58% being female. Mortality, revision, and reoperation were assessed using cumulative incidence with death as a competing risk and Cox regression methods. Clinical outcomes were assessed using Knee Society Scores. A posterior-stabilized design was used in 88%. Mean follow-up was 4 years.The mortality rates were 0%, 2%, 9%, and 47% at 90 days, 1 year, 2 years, and 5 years, respectively. The 5-year cumulative incidences of any revision and reoperation were 0% and 3%, respectively. The reoperations included 2 internal fixations for periprosthetic fracture and 1 hardware removal. The mean Knee Society Score improved significantly from 34 preoperatively to 80 at 5 years (P.001). The 5-year cumulative incidence of any nonmortality complication was 66%. The most common complications were urinary tract infections and retention (8%) in the early postoperative period, and acquired idiopathic stiffness (10%) later.Nonagenarians undergoing primary TKA had low mortality rates at 90 days (0%) and 1 year (2%) with substantial functional improvements. The cumulative incidences of revision and reoperation were low at 5 years.Level IV, retrospective cohort.

Background The incidence of spinal column tumours is estimated to be 0.62 per 100,000 individuals in the US. It is especially important to understand the incidence and predictive factors for adverse events of surgery in spinal oncology patients, as a single complication may be associated with morbidity, mortality, and costs. The aim of the study was to use a large national registry to evaluate the perioperative cumulative incidence and predictors of major complications, for metastatic spinal tumours. Methods This study is a retrospective analysis of data from the DWG registry on patients who have undergone decompression with and without instrumentation undergoing tumour debulking, release of the neural structures, spinal stabilisation or tumour extirpation in metastatic disease of the spine in 124 departments from January 2017 to January 2020, as well as vertebroplasty and percutaneous instrumentation (MIS). The outcomes evaluated were major complications defined by Finkelstein et al. as: death; cerebral (new postoperative coma or stroke), cardiac, pulmonary or renal complication; symptomatic venous thromboembolism (VTE); surgical site infection (SSI). Results In total, 1617 decompressions with and without instrumentation undergoing tumour debulking, release of the neural structures, spinal stabilisation or tumour extirpation in metastatic disease in the spine were identified in the registry; n=266 developed a major complication (group 2), while n= 1351 had no complication (group 1). The mean age in group 1 was 65 years (58.5%), in group 2 69 years (63.5%). In group 2, most of the patients had preoperatively an ASA score of 3 and 4 (patients with severe general disease): 202/266 (75.9%) being significant. The overall prevalence of a major postoperative complication was 16.5% and for an intraoperative complication remained 8%. The likelihood ratio (OR) for major complications by blood loss greater than 500 ml were as follows: cardiovascular event with a likelihood of 4.22 pulmonary insufficiency 4.18 and cerebral 5.47. Conclusions This analysis provides predictive models for surgeons to identify patients who may benefit from transitional care programmes. Preoperative status, invasiveness, blood loss> 500 ml and blood transfusions are independent predictors associated with higher risk of complication.

Highlights • Resource constraints have led to prolonged wait-times for prostate brachytherapy. • Increased wait times predict a significant increase in recurrence and metastases. • Better resource planning is needed to reduce management delays & improve outcomes., Purpose It has previously been shown that increased wait times for prostatectomy are associated with poorer outcomes in intermediate-risk prostatic carcinoma (PCa). However, the impact of wait times on PCa outcomes following low-dose-rate brachytherapy (LDR-BT) are unknown. Methods and Materials We retrospectively reviewed 466 intermediate-risk PCa patients that underwent LDR-BT at a single comprehensive cancer center between 2003 and 2016. Wait times were defined as the time from biopsy to LDR-BT. The association of wait times with outcomes was evaluated using Cox and Fine-Gray regression in both univariate and multivariate models. Results Median (interquartile range) follow-up and wait time for all patients were 8.1 (6.3–10.4) years and 5.1 (3.9–6.9) months, respectively. Among NCCN unfavourable intermediate-risk (UIR) patients (n = 170; 36%), increased wait times predicted both a greater cumulative incidence of recurrence [MHR = 1.01/month of wait time (95% CI: 1.00–1.03); P = 0.044] and metastases [MHR = 1.04/month of wait time (95% CI: 1.02–1.06); P

Background The implantation of rapid-deployment aortic valves may interfere with the conduction system of the heart. This study evaluates the occurrence and predictive factors of conduction anomalies in patients undergoing surgical aortic valve replacement (SAVR) with a rapid-deployment balloon-expandable bioprosthesis in a single-center, real-world experience. Methods Between May 2010 and April 2019, 700 consecutive patients were included in a prospective, ongoing database with a longitudinal follow-up preoperatively, at discharge, and at 3 months, 1 year, 3 years, and 5 years postoperatively. Thirty-seven patients (5.3%) had a permanent pacemaker at baseline and were excluded from further analysis, leaving 663 patients for analysis. Assessment of conduction anomalies was performed by electrocardiography (ECG) monitoring and repeated 12-lead ECG during the hospital stay and at postoperative follow-ups. Results Preoperatively, 126 patients (19.0%) presented with different conduction disturbances. New permanent pacemaker implantation (PPI) occurred in 61 patients during the first 14 days (cumulative incidence, 9.4%). The indication for PPI was complete atrioventricular block in 47 cases (77%). Preoperative conduction anomalies, such as right bundle branch block, as well as operative characteristics (concomitant procedures) were found to be independent predictors for new PPI. One-year survival was 98% in patients with new early PPI and 96% in those without new early PPI (P = .60). Conclusions The PPI rate was in the range of previous reports for rapid-deployment prostheses. PPI did not have a significant influence on short- to intermediate-term survival. Case selection with exclusion of patients presenting with baseline conduction disturbances may decrease the rate of new PPIs after SAVR with rapid-deployment balloon-expandable bioprostheses.

Accelerated partial breast irradiation (APBI) represents a validated technique for low-risk breast cancer. Recently, ultra-APBI (uAPBI) using fewer than 5 fractions was described in the literature. We compared clinical outcomes and late toxicity after APBI or uAPBI in older patients.Two cohorts of older patients (aged ≥70 years) with low-risk breast cancer treated with APBI (interstitial brachytherapy) were analyzed retrospectively. A total dose of 34 Gy in10 fractions (APBI) or 16 Gy in 1 fraction (uAPBI) was delivered from 2004 to 2012 and from 2013 to 2018, respectively. Oncologic outcome analyzed the cumulative incidence of local relapse, regional relapse, and distant metastases with disease-free survival, cause-specific survival, and overall survival. Late toxicity and cosmetic results were investigated.One hundred fifty-seven patients (APBI, n = 109 patients; uAPBI, n = 48 patients) underwent APBI according to the same selection criteria. Apart from the median follow-up (97 vs 72 months for APBI and uAPBI; P.002), no significant difference was noted between the 2 groups. Regarding 6-year oncologic outcome, no significant difference was observed between APBI and uAPBI for local recurrence (1.3% vs 0%; P = .4), regional recurrence (2.5% vs 2.3%; P = .9), distant metastases (4.3% vs. 2.4%; P = .6), disease-free survival (85.2% vs. 82.2%; P = .8), cause-specific survival (96.7% vs. 96.2%; P = .9), and overall survival (86.7% vs. 82.2%; P = .7). Regarding late toxicity, no significant difference was observed between APBI and uAPBI (total complication number, 45 vs 33%; P = .173) with only grade 1 (88.4% vs. 95%) and grade 2 (11.6% vs. 5%) late toxicities (P = .677). Similarly, no significant difference was observed for excellent/good cosmetic results between the 2 cohorts (P = .98).We report the first study comparing APBI versus uAPBI in a cohort of older patients with low-risk breast cancer. No significant difference was found between the 2 treatment groups regarding oncologic outcome, late toxicity, and cosmetic result. uAPBI based on a single fraction of brachytherapy represents an attractive option for therapeutic de-escalation in older patients with breast cancer.

OBJECTIVE Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG. METHODS A total of 1245 pediatric patient (aged 0–17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non–EBRT-treated pediatric patients. RESULTS In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90–6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31–13.00) compared with 4.99% (95% CI 4.38–12.23) in the non–EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21–4.20; p = 0.010). CONCLUSIONS Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population

OBJECTIVES The HeartWare HVAD (HW) and the HeartMate3 (HM3) are presently the most commonly used continuous-flow left ventricular assist devices worldwide. We compared the outcomes of patients supported with either of these 2 devices based on data from the EUROMACS (European Registry for Patients with Mechanical Circulatory Support). METHODS A retrospective analysis of the survival and complications profile in propensity score-matched adult patients enrolled in the EUROMACS between 01 January 2016 and 01 September 2020 and supported with either an HW or HM3. Matching included demographic parameters, severity of cardiogenic shock and risk-modifying end-organ parameters that impact long-term survival. Survival on device and major postoperative adverse events were analysed. RESULTS Following 1:1 propensity score matching, each group consisted of 361 patients. Patients were well balanced ( CONCLUSIONS Mid-term survival in both groups was similar in a propensity-matched analysis. The risk of device malfunction, neurological dysfunction and intracranial bleeding was significantly higher in HW patients.

Objectives Balloon postdilation (BPD) is one strategy for decreasing paravalvular leakage, but its effect on long-term mortality remains unclear. The authors sought to clarify whether BPD influences long-term mortality of patients with transcatheter aortic valve replacement (TAVR). Design Single-center retrospective study. Setting National heart center; single institution. Participants Participants were patients who underwent TAVR in the authors’ hospital from January 2014 to December 2016. A balloon-expandable Sapien XT or Sapien3, or self-expandable CoreValve or Evolute R, was implanted according to the decision of the surgeon considering degree of calcification of the aortic valve. Interventions No interventions. Measurements and Main Results Multivariate Cox regression analysis and inverse probability weighted estimation were performed using a propensity score to examine whether BPD influenced six-year mortality. Ultimately, 180 patients were analyzed. During the follow-up period, with a median of 1104 (interquartile range: 730-1463) days, 41 patients died and cumulative incidence of mortality at six years was 22.8%. Society of Thoracic Surgeons score (odds ratio [OR]: 2.257, 95% CI: 1.213-4.197, p = 0.010)], BPD (OR: 0.306, 95% CI: 0.098-0.953, p = 0.041), and paravalvular regurgitation of at least moderate-to-mild severity after deploying (OR: 5.407, 95% CI: 1.626-17.978, p = 0.006) were significant factors of mortality. Conclusions BPD is associated with reduced six-year mortality.

Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLC patients receiving these treatments.A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of VTEs after ICIs was estimated using competing risk analysis, and the association of these events with survival and response to treatment was determined. Finally, univariate and multivariate tests were performed to identify VTE risk factors.The cumulative incidence of VTEs in the cohort was 14.8% (95% CI = 7.4-22.2%) for an incidence rate of 76.5 (95% CI = 59.9-97.8) thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. VTEs were not correlated with overall survival, progression-free survival, or objective response to ICIs. Age ˂ 65 years old (HR = 2.00; 95% CI = 1.11-3.59) and tumors with PD-L1 1-49% (HR = 3.36; 95% CI = 1.19-9.50) or PD-L1 ≥ 50% (HR = 3.22; 95% CI = 1.21-8.57) were associated with more VTEs after 12 months of ICI initiation. Also, a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 2.06; 95% CI = 1.09-3.89) and active smoking (HR = 2.00; 95% CI = 1.12-3.58) are probable risk factors of VTEs.This study suggests that the incidence of VTEs in NSCLC patients treated with ICIs is comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, VTEs were not associated with a decreased survival or response to therapy. Patient age 65 and tumors with PD-L1 ≥ 1% were associated with a higher risk of VTEs under ICIs.

Background Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD currently is unknown. Research Question What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD? Methods We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis [IPF]) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-min walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality or transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the ILD-GAP-O2 model), which included oxygenation status as a predictor. Results The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1%, respectively, for exertional hypoxemia and 2.4%, 5.6%, and 16.5%, respectively, for resting hypoxemia, which were significantly higher in patients with IPF compared with patients without IPF (P Interpretation Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.

Objective Transrectal ultrasound guided biopsy for diagnostic workup for prostate cancer (PCa) has a substantial false negative rate. We sought to estimate PCa incidence and mortality following negative biopsy in a cohort of men undergoing prostate cancer screening. Subjects and Methods The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial randomized participants 55-74 years to an intervention vs control arm. Intervention arm men received annual prostate-specific antigen (PSA) tests for 6 years and digital rectal exams (DRE) for 4 years. We examined the cohort of men with a positive PSA (> 4 ng/mL) or DRE screen followed within one year by a negative biopsy. PCa incidence and mortality rates from time of first negative biopsy were analyzed as a function of PSA level at diagnosis and other factors. Cumulative incidence and mortality rates accounting for competing risk were estimated. Multivariate proportional hazards regression was utilized to estimate hazard ratios (HRs) of PCa outcomes by PSA level, controlling for age and race. Results The negative biopsy cohort included 2855 men. Median (25th/75th) age at biopsy was 65 (61/69) years; biopsies occurred between 1994 and 2006. Median (25/75th) follow-up was 13.2 (6.5/16.8) years for incidence and 16.6 (12.3/19.2) years for mortality. 740 PCa cases were diagnosed, with 33 PCa deaths. Overall 20-year cumulative PCa incidence and mortality rates were 26.4% (95% CI: 24.8-28.1) and 1.2% (95% CI: 0.9-1.7), respectively. HRs for PCa incidence and mortality increased significantly with increasing PSA. Conclusion The mortality rate from PCa through 20 years following a negative biopsy is low.

OBJECTIVE The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). METHODS Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. RESULTS Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. CONCLUSION Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.

IntroductionHearing loss and insomnia emerged as preeminent sources of morbidity among military service members and veterans who served in the recent Iraq and Afghanistan conflicts. Significant threshold shift (STS), an early indicator of hearing loss, has not been studied in relation to insomnia. This study’s objective was to examine the co-occurrence of STS and insomnia among U.S. military personnel with blast-related injury.Materials and MethodsA total of 652 service members who were blast-injured during military operations in Iraq or Afghanistan between 2004 and 2012 were identified from the Blast-Related Auditory Injury Database. Pre- and post-injury audiometric data were used to ascertain new-onset STS, defined as 30 dB or greater increase for the sum of thresholds at 2,000, 3,000, and 4,000 Hz for either ear. Insomnia diagnosed within 2 years post-injury was abstracted from electronic medical records. Multivariable logistic regression analysis examined the relationship between STS and insomnia, while adjusting for age, year of injury, occupation, injury severity, tinnitus and concussion diagnosed in-theater, and PTSD.ResultsA majority of the study sample was aged 18-25 years (79.9%) and sustained mild-to-moderate injuries (92.2%). STS was present in 21.1% of service members. Cumulative incidence of diagnosed insomnia was 22.3% and 11.1% for those with and without STS, respectively. After adjusting for covariates, those with STS had nearly 2-times higher odds of insomnia (odds ratio (OR) = 1.91, 95% CI = 1.12-3.24) compared with those without STS. In multivariable modeling, the strongest association was between PTSD and insomnia (OR = 5.57, 95% CI = 3.35-9.26). A secondary finding of note was that military personnel with STS had a significantly higher frequency of PTSD compared with those without STS (28.1% vs. 15.2%).ConclusionsHearing threshold shift was associated with insomnia in military personnel with blast-related injury and could be used to identify service members at risk. Multidisciplinary care is needed to manage the co-occurrence of both conditions during the post-deployment rehabilitation phase. Future research should evaluate the specific mechanisms involved in this relationship and further explore the association between hearing threshold shift and PTSD.

OBJECTIVES The aim of this study was to evaluate technical/clinical outcomes of the Gore TAG Conformable Thoracic Stent Graft with Active Control System (CTAG with ACS) in thoracic aortic disease since its introduction in Europe in 2017. METHODS Patients undergoing thoracic endovascular aortic repair (TEVAR) with the device between 2017 and 2020 were identified from a prospectively maintained single-centre database and retrospectively analysed. Predominant indications were aortic dissection (n = 46), thoracic/thoraco-abdominal aneurysm (n = 20/n = 7), penetrating ulcer (n = 14) and intramural haematoma (n = 12). Emergency procedures were performed in 47% (54/115). The primary outcome was technical success. Secondary outcomes were clinical success, serious adverse events and procedure-related reintervention. ACS was assessed regarding angulation, accuracy and apposition. The median follow-up was 8.46 months (interquartile range: 3.18–16.89 months). RESULTS A total of 115 consecutive patients (82 males, median age 63; interquartile range: 53–74 years) have been included. Technical success was achieved in 95.7% (110/115). Clinical success rate was 80.9% (93/115); mostly due to procedure-related death (n = 14). Overall mortality was 19.1% (22/115), with significant differences between elective/emergency procedures (log-rank: P CONCLUSIONS This single-centre study shows encouraging performance of the CTAG with ACS in an array of aortic pathologies. Although longer-term data must be awaited, ACS leads to overall favourable device placement. Despite ongoing advances in device technology, TEVAR remains challenging and is associated with significant burden inherent to the underlying disease.

Background Development of depression in prostate cancer patients depends on multiple disease- and patient-related factors. Objective To investigate the risk of depression following radical prostatectomy focussing on the impact of surgery and subsequent treatment with salvage radiation or androgen deprivation therapy. Design, setting, and participants A population-based cohort study of 5570 men who underwent radical prostatectomy in Denmark from 1998 to 2011 was identified in the Danish Prostate Cancer Registry. Outcome measurements and statistical analysis Data on covariates and primary outcome defined as a hospital contact for depression or a redeemed antidepressant prescription were obtained from nationwide Danish registries. The risk of depression was evaluated using cumulative incidence functions and Cox models with time since surgery as an underlying time scale. Exposure to salvage procedures was included as time-varying covariates, and analyses were adjusted for confounders. Results and limitations The cumulative incidence of depression was increased in men who had undergone surgery compared with cancer-free men throughout follow-up of up to 18 yr, particularly among men on androgen deprivation therapy. Compared with no subsequent treatment, the risk of depression was increased with subsequent androgen deprivation therapy (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.4–2.3), salvage radiation (HR 1.3, 95% CI 1.0–1.6), and the treatments combined (HR 2.2, 95% CI 1.8–2.8) after adjustments for age, year of surgery, income, and cohabitation status. Further adjustment for comorbidity hardly changed the estimates. Conclusions Radical prostatectomy and subsequent salvage procedures increase the risk of depression, and men with subsequent androgen deprivation therapy are mainly at risk. Clinicians should thus be aware of depressive symptoms in patients receiving treatment for postsurgical relapse. Patient summary In a population-based study, we found that radical prostatectomy and subsequent treatments with either radiation or endocrine manipulation significantly increased the risk of developing clinical depression.

Objectives: Patients with ovarian cancer have been shown to have high rates of venous thromboembolism (VTE), with previous studies reporting an up to 16% overall incidence of symptomatic VTE, and a 7.5% cumulative incidence of VTE within the first 30 days after surgery. The goal of this study is to determine the updated incidence and risk factors for VTE for patients with advanced epithelial ovarian cancer undergoing first-line therapy, including cytoreductive surgery, on an Enhanced Recovery After Surgery (ERAS) protocol. Methods: Medical records were reviewed for all patients with FIGO stage IIIA-IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer undergoing primary or interval cytoreductive surgery from March 2017 through September 2019 at a single institution. All patients were enrolled on an ERAS protocol, including 28-day postoperative VTE prophylaxis. Demographic information, past medical history, perioperative characteristics, and ERAS compliance were collected and evaluated using univariate and multivariate Cox proportional hazards models. Download : Download high-res image (86KB) Download : Download full-size image Results: Of 230 patients undergoing cytoreductive surgery via laparotomy, 155 received neoadjuvant chemotherapy and 75 received primary cytoreduction. 38 patients had a VTE during the study period. 13 events (5.7%) were identified at time of diagnosis, 6 (3.9%) during neoadjuvant chemotherapy, 5 (2.2%) within 30 days after surgery, 5 (2.2%) between 30 days and 6 months after surgery, and 9 (3.9%) after the 6-month window. The cumulative incidence of VTE was 6.1% (95% CI, 4.3-8.8%) within 6 months after diagnosis and 8.5% (6.2-11.4%) within 1 year after diagnosis. Estimated blood loss (adjusted HR 1.22 [95% CI, 1.09-1.36], p=0.001) and history of VTE (7.06 [2.34-21.29], p=0.001) were independently associated with VTE. Conclusions: With implementation of an ERAS protocol and 28-day postoperative VTE prophylaxis, only 1 in 46 patients experienced a VTE within 30 days after surgery, a rate markedly lower than historically reported for cytoreductive procedures. However, overall VTE occurred in 1 in 16 patients during first-line therapy. Half of the venous thromboembolic events occurred prior to surgery and 36.8% occurred more than 30 days after surgery. Strategies to further reduce VTE risk, especially during neoadjuvant chemotherapy and surveillance, should be investigated.

Chronic inflammation, a hallmark of gout, is implicated in the pathogenesis of atherosclerosis. Thus, in theory, gout can be expected to increase the risk of acute myocardial infarction (AMI). Yet, results from several epidemiological studies have been inconclusive. A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohort comprised 3581 patients with gout (the gout cohort) and 14,324 patients without gout (the non-gout cohort). The primary outcome was the incidence of AMI. To estimate the effect of gout on the risk of AMI, the Lunn-McNeil competing risk model was fitted to estimate cause-specific hazard ratios (HRs) and their 95% confidence intervals (CIs). The cumulative incidence of AMI was significantly higher in the gout cohort than in the non-gout cohort, resulting in an adjusted HR of 1.36 (95% CI 1.04 to 2.76). Further, HRs of gout with incident AMI were higher in patients without hypertension, diabetes mellitus, or hyperlipidemia (ranging from 1.63 to 2.09) than in those with each of these comorbidities (ranging from 0.95 to 1.13). The results of this study suggest that patients with gout have an increased risk of AMI. The AMI risk associated with gout was conditional on patients’ cardiovascular risk profile. Future work is needed to confirm these findings.

Objective The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). Methods This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients’ demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. Results PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14–1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04–0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. Conclusions CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Background Mentor MemoryGel Breast Implants were approved by the U.S. Food and Drug Administration in November of 2006. Patients in the Core clinical study supporting this approval were followed for 10 years. Methods This prospective, multicenter, clinical study included primary augmentation, revision augmentation, primary reconstruction, and revision reconstruction patients implanted with smooth or Siltex Texture MemoryGel Implants. Incidence, severity, and method of resolution for all postoperative complications were assessed on per-patient and per-implant bases. The primary effectiveness endpoints were overall mean change in chest circumference and bra cup size following the implantation procedure. Results Primary augmentation (n = 552), revision augmentation (n = 145), primary reconstruction (n = 251), and revision reconstruction (n = 60) patients were enrolled in the study. Kaplan-Meier estimated 10-year cumulative incidence rates for key complications at the subject level for Baker grade III/IV capsular contracture were as follows: primary augmentation, 12.1 percent; revision augmentation, 24.4 percent; primary reconstruction, 20.5 percent; and revision reconstruction, 36.9 percent. For infection, rates were as follows: primary augmentation, 1.6 percent; revision augmentation, 1.4 percent; primary reconstruction, 6.2 percent; and revision reconstruction, 0 percent. For explantation with or without replacement, rates were as follows: primary augmentation, 11.6 percent; revision augmentation, 24.1 percent; primary reconstruction, 33.4 percent; and revision reconstruction; 37.8 percent. For rupture, rates were as follows: primary augmentation, 24.2 percent; revision augmentation, 23.7 percent; primary reconstruction, 32.7 percent; and revision reconstruction, 38.7 percent. For any reoperation, rates were as follows: primary augmentation, 25.5 percent; revision augmentation, 43.6 percent; primary reconstruction, 49.0 percent; and revision reconstruction, 50.7 percent. Conclusion The results of this study demonstrate that MemoryGel Implants are safe and effective for use in women undergoing breast augmentation or reconstruction. Clinical question/level of evidence Therapeutic, IV.

Background: Although patients with neuroendocrine tumors (NETs) are known to have prolonged overall survival, the contribution of cancer-specific and noncancer deaths is undefined. This study examined cancer-specific and noncancer death after NET diagnosis. Methods: We conducted a population-based retrospective cohort study of adult patients with NETs from 2001 through 2015. Using competing risks methods, we estimated the cumulative incidence of cancer-specific and noncancer death and stratified by primary NET site and metastatic status. Subdistribution hazard models examined prognostic factors. Results: Among 8,607 included patients, median follow-up was 42 months (interquartile range, 17–82). Risk of cancer-specific death was higher than that of noncancer death, at 27.3% (95% CI, 26.3%–28.4%) and 5.6% (95% CI, 5.1%–6.1%), respectively, at 5 years. Cancer-specific deaths largely exceeded noncancer deaths in synchronous and metachronous metastatic NETs. Patterns varied by primary tumor site, with highest risks of cancer-specific death in bronchopulmonary and pancreatic NETs. For nonmetastatic gastric, small intestine, colonic, and rectal NETs, the risk of noncancer death exceeded that of cancer-specific deaths. Advancing age, higher material deprivation, and metastases were independently associated with higher hazards, and female sex and high comorbidity burden with lower hazards of cancer-specific death. Conclusions: Among all NETs, the risk of dying of cancer was higher than that of dying of other causes. Heterogeneity exists by primary NET site. Some patients with nonmetastatic NETs are more likely to die of noncancer causes than of cancer causes. This information is important for counseling, decision-making, and design of future trials. Cancer-specific mortality should be included in outcomes when assessing treatment strategies.

Contains fulltext : 237504.pdf (Publisher’s version ) (Closed access) INTRODUCTION: The aim of this study was to determine the incidence, location and timing of second primary tumours (SPT) after diagnosis of oral squamous cell carcinoma (OSCC) and relate the risk of SPT to that after head and neck squamous cell carcinoma (HNSCC) and the risks of those tumours in the general population in order to assess the need for a separate follow-up programme for OSCC patients and to aid development of an evidence-based and individualized follow-up programme for OSCC patients. MATERIALS AND METHODS: All patients diagnosed with OSCC or HNSCC in the Netherlands in 1991-2015 were selected from the Netherlands Cancer Registry. Cumulative incidence rates and Standardized Incidence Ratios (SIR) were calculated. Analyses were stratified by incidence period and age at primary diagnosis of the index tumour, follow-up time, and site of the SPT. RESULTS: We included 11263 patients with OSCC from a population of 34244 patients with HNSCC, of which the median follow-up time was 4.0 years. OSCC SPT develop in different patterns and at different locations than after HNSCC. The 5-year risk of SPT and SIR (95% confidence intervals) were respectively 0.13 (0.13-0.14) and 3.0 (2.9-3.1) for OSCC. The risk of a SPT was continuous over follow-up time and calendar period but decreased with an increasing age at diagnosis of the index tumour up to the age of 75 and there were differences in sites of SPT. CONCLUSION: A specific follow-up protocol for OSCC is needed, which can be individualized on the basis of, among others, age.

Purpose: To date, studies regarding the use of prophylactic cranial irradiation (PCI) versus standard of care (SoC) for patients with non-small cell lung cancer (NSCLC) have not shown a significant effect in terms of overall survival (OS). Additionally, the effect of PCI among high-risk patients has been scarcely studied. The objective of this randomized phase 2 study was to evaluate the role of PCI in a population of patients at high risk for development of brain metastases (BM). Methods and Materials: Eligible patients had histologically confirmed NSCLC without baseline BM, harboring epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels at the time of diagnosis. Participants received systemic therapy according to molecular status, those without progressive disease were then assigned to receive SoC or SoC thorn PCI (25 Gy in 10 fractions). The primary outcome was cumulative incidence of brain metastases (CBM). The secondary endpoints included progression-free survival and OS. Quality of life and neurocognitive function are discussed in a separate article (Clinicaltrials.gov: NCT01603849). Results: From May 2012 to December 2017, 84 patients were enrolled in the study, with 41 patients allocated to receive PCI and 43 received SoC. Patients allocated to receive PCI had a CBM at 24 months of 7% versus 38% in those allocated to the SoC arm. PCI was associated with a hazard ratio of 0.12 (95% confidence interval, 0.035-0.42) for developing BM. A benefit in OS was also observed (64.5 vs 19.8 months; hazard ratio: 0.41 (95% confidence interval, 0.22-0.78; P = .007). Conclusions: Among a selected population at high risk for developing BM, PCI significantly decreased CBM in addition to increasing progression-free survival and OS. To our knowledge, this is the first study to evaluate PCI in epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels in patients with NSCLC, showing a significant improvement in CBM. This relevant information should be of particular importance in the context of patients without access to third-generation targeted agents. Further studies are warranted to ascertain this effect. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND: COVID-19 has quickly spread throughout the world, necessitating assessment of effective containment methods. The purpose of this study was to examine the impact of government mandated school closures, stay at home orders and mask requirements METHODS: Cumulative incidence rates were calculated at 14-day intervals until the day of the first vaccine administration in the country. Rate ratios were calculated using negative binomial regression while investigating the effects of adjusting for several sociodemographic and medical factors RESULTS: Faster implementation of mask mandates was consistently shown to be protective. States with mask mandates made at three to six months had a 1.61 times higher rate than those who implemented within one month (adjusted rate ratio = 1.61, 95% confidence interval: 1.23-2.10, P = .001). States with mask mandates made after 6 months or with no mandate had a 2.16 times higher rate than those who implemented within 1 month (adjusted rate ratio = 2.16, 95% confidence interval: 1.64-2.88, P < .0001). In contrast, both stay at home orders and school closures had no significant influence on disease trajectory. DISCUSSION: The benefits of mask mandates are apparent, especially when mandates were issued within a month. The impact of school closing and stay at home orders were less clear. CONCLUSIONS: Our results suggest that of the different physical distancing measures implemented by the government, mask mandates are the most important.

Aims: Therapy with phosphodiesterase-5 inhibitors (PDE5Is) after left ventricular assist device (LVAD) implantation has been associated with lower mortality and device thrombosis but increased risk for post-operative and gastrointestinal bleeding. We aimed to evaluate the impact of long-term PDE5Is on the overall bleeding risk after LVAD implantation. Methods and results: We retrospectively included patients who received a continuous-flow LVAD at our site and were prescribed with long-term oral PDE5Is after discharge from the index hospitalization. The primary endpoint was the occurrence of bleeding at 12 month follow-up. Secondary endpoints were all-cause death and the combination of bleeding and all-cause death. Our analysis included 109 patients of whom 75 (69%) received long-term PDE5Is. Mean age was 56 years, and 85% were male. At 12 months, 19 (17%) patients experienced at least one bleeding event. Patients on PDE5Is had higher bleeding rates (23% vs. 6%, P = 0.03) and more bleeding events per patient-year (0.32 vs. 0.06, P = 0.03) compared with patients not on PDE5Is. While overall bleeding incidence was excessively higher in the PDE5I group, there were no significant differences in the incidence of major bleeding (19% vs. 6%, P = 0.08) and gastrointestinal bleeding (11% vs. 3%, P = 0.18). Kaplan–Meier analysis revealed higher cumulative incidence of bleeding for the PDE5I group (log rank = 0.04) with no difference on all-cause death (log rank = 0.67) and the combination of bleeding and all-cause death (log rank = 0.13). Hospitalizations for bleeding and their duration were numerically higher in the PDE5I group (0.28 vs. 0.03, P = 0.07 and 2.4 vs. 0.2, P = 0.07, respectively). Conclusions: Phosphodiesterase-5 inhibitor treatment after LVAD implantation is associated with increased bleeding risk after LVAD implantation. The safety of long-term PDE5Is in LVAD patients remains unclear and needs to be further clarified in prospective studies with randomized study design. OA Förderung 2021

Purpose Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement. Methods and Materials For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction. Results Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]). Conclusions For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy.