Cumulative Incidence Function Research Articles

Pneumonitis Rates Before and After Adoption of Immunotherapy Consolidation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation

We hypothesized that after adoption of immune checkpoint inhibitor (ICI) consolidation for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy (cCRT), rates of symptomatic pneumonitis would increase, thereby supporting efforts to reduce lung radiation dose. This single institution, multisite retrospective study included 783 patients with LA-NSCLC treated with definitive cCRT either before introduction of ICI consolidation (pre-ICI era cohort [January 2011-September 2017]; N=448) or afterward (ICI era cohort [October 2017-December 2021]; N=335). Primary endpoint was grade ≥2 pneumonitis (G2P) and secondary endpoint was grade ≥3 pneumonitis (G3P), per Common Terminology Criteria for Adverse Events v5.0. Pneumonitis was compared between pre-ICI era and ICI era cohorts using the cumulative incidence function and Gray's test. Inverse probability of treatment weighting (IPTW)-adjusted Fine-Gray models were generated. Logistic models were developed to predict the 1-year probability of G2P as a function of lung dosimetry. G2P was higher in the ICI era than in the pre-ICI era (1-year cumulative incidence 31.4% vs 20.1%; P < .001; IPTW-adjusted multivariable subdistribution hazard ratio, 2.03; 95% confidence interval, 1.53-2.70; P < .001). There was no significant interaction between ICI era treatment and either lung volume receiving≥20 Gy (V20) or mean lung dose in Fine-Gray regression for G2P; however, the predicted probability of G2P was higher in the ICI era at clinically relevant values of lung V20 (≥24%) and mean lung dose (≥14 Gy). Cut-point analysis revealed a lung V20 threshold of 28% in the ICI era (1-year G2P rate 46.0% above vs 19.8% below; P < .001). Among patients receiving ICI consolidation, lung V5 was not associated with G2P. G3P was not higher in the ICI era (1-year cumulative incidence 7.5% vs 6.0%; P=.39; IPTW-adjusted multivariable subdistribution hazard ratio, 1.12; 95% confidence interval, 0.63-2.01; P=.70). In patients with LA-NSCLC treated with cCRT, the adoption of ICI consolidation was associated with an increase in G2P but not G3P. With ICI consolidation, stricter lung dose constraints may be warranted.

Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study

Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

The impact of cardiovascular disease on all-cause and cancer mortality: results from a 16-year follow-up of a German breast cancer case–control study

BackgroundCardiovascular disease (CVD) is the leading cause of death worldwide. The aim of this study was to examine if CVD affects the mortality of women after a breast cancer diagnosis and population controls differently.MethodsThe analysis included a total of 3,555 women, diagnosed with primary stage 1–3 breast cancer or in situ carcinoma between 2002 and 2005 and 7,334 controls breast cancer-free at recruitment, all aged 50–74 years, who were followed-up in a German breast cancer case–control study until June, 30 2020. Kaplan–Meier and cumulative incidence function were calculated for all-cause mortality and mortality from any cancer, stratified for case–control status and CVD, separately for women aged < 65 and ≥ 65 years. Cox regression and Fine-Gray subdistribution hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between case–control-status, CVD and mortality from all causes/any cancer.ResultsThe median follow-up was 16.1 years. In total, 1,172 cases (33.0%) and 1,401 initial controls (19.1%) died. CVD prevalence at recruitment was 15.2% in cases and controls. Cases with CVD had the highest and controls without CVD the lowest mortality during the entire observation period in both age groups (< 65 and ≥ 65 years). CVD was identified as a risk factor for all-cause mortality in both cases and controls aged < 65 years (HR 1.22, 95%CI 0.96–1.55 and HR 1.79, 95%CI 1.43–2.24) as well as at ages of ≥ 65 years (HR 1.44, 95%CI 1.20–1.73 and HR 1.59, 95%CI 1.37–1.83). A significant association of CVD and cancer mortality was found only for cases aged ≥ 65 years.ConclusionCVD was significantly associated with all-cause mortality of both cases and controls and CVD was identified as a risk factor for cancer mortality of cases aged ≥ 65 years at recruitment. Therefore, attention should be paid on monitoring and preventing CVD in breast cancer patients, especially in those diagnosed at older ages.

Incidence of chronic disease following smoking cessation treatment: A matched cohort study using linked administrative healthcare data in Ontario, Canada.

Scarce evidence is available on the impact of real-world smoking cessation treatment on subsequent health outcomes, such as incidence of chronic disease. This study compared two cohorts of people that smoke-those that enrolled in a smoking cessation program, and a matched control that had not accessed the program-to assess the incidence of cancer, chronic obstructive pulmonary disease, diabetes, hypertension, and major cardiovascular events over a 5-year follow-up period. We selected five sub-cohorts with matched treatment-control pairs in which both individuals were at risk of the five chronic diseases. Incident chronic disease from index date until December 31, 2017, was determined through linkage with routinely collected healthcare data. The cumulative incidence of each chronic disease was estimated using the cumulative incidence function with death as a competing risk. Gray's test was used to test for a difference between matched treatment and control groups in the chronic disease-specific cumulative incidence function over follow-up. Analyses were stratified by sex. Among females, cumulative incidence of diabetes was higher over follow-up for the treatment group (5-year cumulative incidence 5.8% vs 4.2%, p = 0.004), but did not differ for the four other chronic diseases. Among males, cumulative incidence of chronic obstructive pulmonary disease (12.2% vs 9.1%, p < 0.001) and diabetes (6.7% vs 4.8%, p < 0.001) both had higher 5-year cumulative incidence for the treated versus control groups but did not differ for the other three chronic diseases. We conclude that accessing primary-care based smoking cessation treatment is associated with increased incidence of diabetes for both sexes, and chronic obstructive pulmonary disease for males (possibly due to under diagnosis prior to treatment), within 5 years of treatment. The associations detected require further research to understand causal relationships.

Respiratory infections predominate after day 100 following B-cell maturation antigen–directed CAR T-cell therapy

AbstractInfections are an important complication after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy and risks may differ between the early and late periods. We evaluated infections in 99 adults who received a first BCMA–directed CAR T-cell therapy (commercial and investigational autologous BCMA CAR T-cell products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded until day 365, if patients experienced symptoms with a microbiologic diagnosis, or for symptomatic site-specific infections treated with antimicrobials. One-year cumulative incidence functions were calculated based on time to first respiratory infection using dates of infection-free death and receipt of additional antineoplastic therapies as competing risks. Secondary analysis evaluated risk factors for late respiratory infections using univariate and multivariable Cox regression models. Thirty-seven patients (37%) experienced 64 infectious events over the first year after BCMA–directed CAR T-cell therapy, with 42 early infectious events (days, 0-100), and 22 late infectious events (days, 101-365). Respiratory infections were the most common site-specific infection and the relative proportion of respiratory infections increased in the late period (31% of early events vs 77% of late events). On multivariable analysis, hypogammaglobulinemia (hazard ratio [HR], 6.06; P = .044) and diagnosis of an early respiratory viral infection (HR, 2.95; P = .048) were independent risk factors for late respiratory infection. Respiratory infections predominate after BCMA CAR T-cell therapy, particularly after day 100. Hypogammaglobulinemia and diagnosis of an early respiratory infection are risk factors for late respiratory infections that may be used to guide targeted preventive strategies.

On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B

The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US. Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment. Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC. Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC. In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.

Evaluation of laboratory values affecting mortality of end-stage renal disease patients: a competing risks approach

BackgroundChronic Kidney Disease (CKD) is a prevalent and life-threatening situation recognized as an emerging health issue. The present study aimed to evaluate the effect of demographic and laboratory parameters on the survival of patients with End-Stage Renal Disease (ESRD) in a hemodialysis (HD) center in Iran.Materials and methodsThis study was conducted on patients receiving chronic HD in Iran Helal Pharmaceutical and Clinical Complex between 2014 and 2018. The survival time was considered as the time interval between HD initiation and death. Receiving kidney transplantation was regarded as a competing risk, and an improper form of two-parameter Weibull distribution was utilized to simultaneously model the time to both death and renal transplantation. The Bayesian approach was conducted for parameters estimation.ResultsOverall, 29 (26.6%) patients expired, and 19 (17.4%) received kidney transplants. The male gender was related to poor survival, having nearly 4.6 folds higher hazard of mortality (90% HPD region: 1.36–15.49). Moreover, Serum calcium levels ge9.5 mg/dL (adjusted Sub-hazard ratio (S-HR)=2.33, 90% HPD region: 1.05–5.32) and intact parathyroid hormone (iPTH) le150 pg/mL (adjusted S-HR = 2.56, 90% HPD region: 1.09–6.15) were associated with an elevated hazard of mortality. The cumulative incidence function (CIF) for transplantation was greater than death in the first two years of the study. Subsequently, the CIF for death exceeded transplantation in the following two years. The 4-year cumulative incidence of death and kidney transplantation was 63.7% and 36.3%, respectively.ConclusionMale gender, hypercalcemia, and hypoparathyroidism were associated with worse outcomes. Correcting mentioned laboratory parameters may improve patients’ survival in the HD population.

Importance of familial predisposition to heart failure to the risk of anthracycline-related cardiotoxicity: A nationwide study

Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF. Using nationwide Danish registries, all patients treated with anthracycline from 2004 to 16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model. A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with preanthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n=1,608) 35 patients (2.2%) were diagnosed with HF vs 133 (1.3%) in the group without a first-degree relative with HF (n=10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, P=.004); adjusted hazard ratio 1.53 (CI:1.05-2.23, P=.03). In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity.

Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer.

We report the outcomes of cisplatin-ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel. We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Sixty-five patients were identified with median age of 71 years (range 44-85). Median radiation dose was 70 Gy and the median doses of carboplatin and paclitaxel were AUC 1 and 40 mg/m2 , respectively. At a median follow-up of 29 (range 5-91) months, the 2-year rates of LRR, DM, PFS, and OS were 8.8%, 9.4%, 72.2%, and 88.7%, respectively. In total, there were 5 LRR, 7 DM, and 12 deaths. Chemoradiation with carboplatin and paclitaxel is an excellent option for cisplatin-ineligible HNSCC patients.

Valve-in-valve transcatheter aortic valve replacement versus isolated redo surgical aortic valve replacement

ObjectiveTo compare outcomes of patients undergoing valve-in-valve transcatheter aortic valve replacement (ViV TAVR) versus redo surgical aortic valve replacement (SAVR). MethodsThis was a retrospective study using institutional databases of transcatheter (2013-2022) and surgical (2011-2022) aortic valve replacements. Patients who underwent ViV TAVR were compared with patients who underwent redo isolated SAVR. Clinical and echocardiographic outcomes were analyzed. Kaplan-Meier survival estimation and Cox regression were performed. Cumulative incidence functions were generated for heart failure readmissions. ResultsA total of 4200 TAVRs and 2306 isolated SAVRs were performed. Of these, there were 198 patients who underwent ViV TAVR and 147 patients who underwent redo SAVR. Operative mortality was 2% in each group, but observed to expected operative mortality in the redo SAVR group was higher than in the ViV TAVR group (1.2 vs 0.32). Those who underwent redo SAVR were more likely to require transfusions and reoperation for bleeding, to have new-onset renal failure requiring dialysis, and to require a permanent pacemaker postoperatively than those in the ViV group. Mean gradient was significantly lower in the redo SAVR group than in the ViV group at 30 days and 1 year. Kaplan-Meier survival estimates at 1 year were comparable, and on multivariable Cox regression, ViV TAVR was not significantly associated with an increased hazard of death compared with redo SAVR (hazard ratio, 1.39; 95% CI, 0.65-2.99; P = .40). Competing-risk cumulative incidence estimates for heart-failure readmissions were higher in the ViV cohort. ConclusionsViV TAVR and redo SAVR were associated with comparable mortality. Patients who underwent redo SAVR had lower postoperative mean gradients and greater freedom from heart failure readmissions, but they also had more postoperative complications than the VIV group, despite their lower baseline risk profiles.

Outcomes for Malignant Pleural Effusions Because of Melanoma Treated With Indwelling Pleural Catheters.

Indwelling pleural catheters (IPCs) reduce dyspnea and improve quality of life in patients with malignant pleural effusions (MPEs). Data on outcomes of MPEs secondary to metastatic melanoma managed with IPCs are scarce. We aimed to evaluate outcomes of patients receiving IPCs for MPEs secondary to melanoma compared with other malignancies. We identified patients from our prospectively collected database of all patients who had an IPC insertion for MPEs at our tertiary care center for melanoma between May 2006 and November 2018 and for nonmelanoma between May 2006 and June 2013. Chart reviews were conducted to obtain patient demographics, catheter complications, time of IPC removal or death, x-ray imaging, and pleural fluid characteristics. We identified 27 MPEs because of melanoma and 1114 because of nonmelanoma malignancies treated with IPC. The most frequent complication was pleural fluid loculation requiring fibrinolytics which was significantly higher in the melanoma (14.8%) compared with the nonmelanoma group (3.8%; P=0.02). Cumulative incidence functions for catheter removal (P=0.8) or death with catheter in situ (P=0.3) were not significant between melanoma and nonmelanoma groups in competing risk analysis. Baseline radiographic pleural effusion scores were similar, but became significantly higher (increased pleural opacity) in the melanoma group at time points following IPC insertion (P<0.05). MPEs because of melanoma had a higher rate of loculations requiring fibrinolytics and less radiographic improvement after IPC insertion suggesting this patient subgroup has a more complicated pleural space which may be less responsive to drainage.

Increasing risk of revision due to infection after primary total hip arthroplasty: results from the Nordic Arthroplasty Register Association.

The incidence of periprosthetic joint infection after total hip arthroplasty (THA) may be increasing. We performed time-trend analyses of risk, rates, and timing of revision due to infection after primary THAs in the Nordic countries from the period 2004-2018. 569,463 primary THAs reported to the Nordic Arthroplasty Register Association from 2004 to 2018 were studied. Absolute risk estimates were calculated by Kaplan-Meier and cumulative incidence function methods, whereas adjusted hazard ratios (aHR) were assessed by Cox regression with the first revision due to infection after primary THA as primary endpoint. In addition, we explored changes in the time span from primary THA to revision due to infection. 5,653 (1.0%) primary THAs were revised due to infection during a median follow-up time of 5.4 (IQR 2.5-8.9) years after surgery. Compared with the period 2004-2008, the aHRs for revision were 1.4 (95% confidence interval [CI] 1.3-1.5) for 2009-2013, and 1.9 (CI 1.7-2.0) for 2014-2018. The absolute 5-year rates of revision due to infection were 0.7% (CI 0.7-0.7), 1.0% (CI 0.9-1.0), and 1.2% (CI 1.2-1.3) for the 3 time periods respectively. We found changes in the time span from primary THA to revision due to infection. Compared with 2004-2008, the aHR for revision within 30 days after THA was 2.5 (CI 2.1-2.9) for 2009-2013, and 3.4 (CI 3.0-3.9) for 2013-2018. The aHR for revision within 31-90 days after THA was 1.5 (CI 1.3-1.9) for 2009-2013, and 2.5 (CI 2.1-3.0) for 2013-2018, compared with 2004-2008. The risk of revision due to infection after primary THA almost doubled, both in absolute cumulative incidence and in relative risk, throughout the period 2004-2018. This increase was mainly due to an increased risk of revision within 90 days of THA. This may reflect a "true" increase (i.e., frailer patients or more use of uncemented implants) and/or an "apparent" increase (i.e., improved diagnostics, changed revision strategy, or completeness of reporting) in incidence of periprosthetic joint infection. It is not possible to disclose such changes in the present study, and this warrants further research.

Adverse events after left ventricular assist device implantation linked to psychosocial risk in women and men

Reasons for women's increased probability to experience adverse events (AEs) after left ventricular assist device (LVAD) implantation compared with men's remain uncertain. We explored the role of psychosocial risk in the experience of AEs in women and men. INTERMACS patients receiving a primary continuous-flow LVAD between July2006 and December 2017, median follow-up 13.6 months, were included (n=20,123, 21.3% women). Time-to-event was calculated with cumulative incidence functions for 10 types of AEs separately (e.g., infection, device malfunction), each time accounting for the competing outcomes death, heart transplant, and device explant due to recovery. Event-specific Cox proportional hazard models were run with a binary psychosocial risk variable (including substance abuse, psychiatric diagnosis, limited social support, limited cognition, repeated noncompliance), controlled for covariates. Psychosocial risk was more prevalent in men than in women (21.4% vs 17.5%, p<0.001). Seven out of 10 AEs were more likely in women than in men (e.g., infection 44.5% vs 39.2%, p<0.001). The association of psychosocial risk with each AE was either stronger in women than in men (e.g., device malfunction HRadj 1.29, 95% confidence interval (CI) (1.06-1.56) vs HRadj 1.10, 95% CI (0.97-1.25); rehospitalization HRadj 1.15, 95% CI (1.02-1.29) vs HRadj 1.03, 95% CI (0.97-1.10) or similar between sexes. Independent of clinical parameters, the presence of psychosocial risk is associated with increases in AEs. This suggests that early modification of psychosocial risk factors may have the potential to lower the risk for AEs in this patient population.

Survival After Cryotherapy Versus Radiotherapy in Low and Intermediate Risk Localized Prostate Cancer

BackgroundFocal therapy, including cryotherapy, reduces overtreatment in low- and intermediate-risk prostate cancer (PCa) patients with multiple comorbidities, which seems to increase in popularity compared with whole gland treatment. However, there is currently no consensus regarding the medium-term outcomes of cryosurgery as a prospective alternative to radiotherapy (RT) for such patients. Our study aims to find the available evidence that directly compares the medium-term overall survival (OS) and cancer-specific mortality (CSM) outcomes between cryotherapy and RT in patients with low- and intermediated-risk PCa. Materials and MethodUsing the Surveillance, Epidemiology, and End Results (SEER) database, we identified 47,787 patients with low- and intermediate-risk PCa diagnosed between 2004 and 2015, of which 46,853 (98%) received treatment with RT, while only 934 (2.0%) received treatment with cryotherapy. Kaplan–Meier methods were used to estimateOS and cancer-specific survival (CSS) between the 2 groups. We performed multivariable Cox regression analysis to assess overall mortality (OM), while the cumulative incidence function (CIF) was used to illustrate cancer-specific mortality (CSM) and noncancer-specific mortality (non-CSM) for all patients. Additionally, competing risks regression (Fine-Gray) was implemented to evaluate any differences. After propensity score matching (PSM), all the aforementioned analyses were repeated. After the inverse probability of treatment weighting (IPTW), we repeated Kaplan–Meier methods on OS and CSS, and performed multivariable Cox regression analysis to assess OM in cryotherapy versus RT. Sensitivity analyses were conducted by excluding patients who died of cardiovascular disease. ResultsAfter applying 1:4 PSM to the cryotherapy group with the RT group, the resulting RT cohort consisted of 3,736 patients who were matched with 934 patients in the cryotherapy cohort. The 5‐year OS and cumulative CSM rates for PS-matched groups (N = 4670) receiving cryotherapy (N = 934) or RT (N = 3736) were 89% versus 91.8%, 0.65% versus 0.57, respectively. Multivariable Cox regression analysis demonstrated that cryotherapy was associated with a poorer OS outcome compared to RT (hazard ratio [HR] 1.29, 95% confidence interval [CI]: 1.07-1.55, p < .01). Multivariate competing risk regression analysis revealed that both treatments were not associated with CSS, with HR = 1.07 (95% CI: 0.55-2.08, p = .85). IPTW-adjusted analyses showed that the 5-years OS rates were 89.6% versus 91.8% for cryotherapy versus RT, respectively. Multivariate regression analysis for OS demonstrated that cryotherapy was more likely to have inferior OS in comparison to RT (HR = 1.30; 95%CI: 1.09-1.54; p < .01). The outcome of sensitivity analyses indicates that there was no significant difference in OS and CSS between the 2 groups. ConclusionFor low- and intermediate-risk PCa patients treated by cryotherapy or RT, we could not demonstrate a survival difference. Cryotherapy may be a feasible option as a viable alternative to traditional radiation therapy.

Initiation of eplerenone or spironolactone, treatment adherence, and associated outcomes in patients with new-onset heart failure with reduced ejection fraction: a nationwide cohort study.

The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort. We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage. We included 7479 patients; 653 (9%) on eplerenone and 6840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65vs. 69 years), and more often men (91%vs. 68%), both P<0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30), or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (P<0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (P<0.001). In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone.

Hospital Discharge and Readmissions Before and During the COVID-19 Pandemic for California Acute Stroke Inpatients

BackgroundAcute stroke therapy and rehabilitation declined during the COVID-19 pandemic. We characterized changes in acute stroke disposition and readmissions during the pandemic. MethodsWe used the California State Inpatient Database in this retrospective observational study of ischemic and hemorrhagic stroke. We compared discharge disposition across a pre-pandemic period (January 2019 to February 2020) to a pandemic period (March to December 2020) using cumulative incidence functions (CIF), and re-admission rates using chi-squared. ResultsThere were 63,120 and 40,003 stroke hospitalizations in the pre-pandemic and pandemic periods, respectively. Pre-pandemic, the most common disposition was home [46%], followed by skilled nursing facility (SNF) [23%], and acute rehabilitation [13%]. During the pandemic, there were more home discharges [51%, subdistribution hazard ratio 1.17, 95% CI 1.15-1.19], decreased SNF discharges [17%, subdistribution hazard ratio 0.70, 95% CI 0.68-0.72], and acute rehabilitation discharges were unchanged [CIF, p<0.001]. Home discharges increased with increasing age, with an increase of 8.2% for those ≥85 years. SNF discharges decreased in a similar distribution by age. Thirty-day readmission rates were 12.7 per 100 hospitalizations pre-pandemic compared to 11.6 per 100 hospitalizations during the pandemic [p<0.001]. Home discharge readmission rates were unchanged between periods. Readmission rates for discharges to SNF (18.4 vs. 16.7 per 100 hospitalizations, p=0.003) and acute rehabilitation decreased (11.3 vs. 10.1 per 100 hospitalizations, p=0.034). ConclusionsDuring the pandemic a greater proportion of patients were discharged home, with no change in readmission rates. Research is needed to evaluate the impact on quality and financing of post-hospital stroke care.

The Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Clinical Stage I Lung Adenocarcinoma

This study investigated the prognostic impact of epidermal growth factor receptor (EGFR) mutation in clinical stage I lung adenocarcinoma patients. Data for 952 patients who received surgical resection and underwent detection of oncogenic driver mutations were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. The adjusted hazard ratio (aHR) with 95% CI of the prognosticator was calculated by Cox proportional hazards model, and cumulative incidence function was measured by competing risk regression model. EGFR mutation was detected in 581 patients (61.0%) and was more frequent in women (63.9%), nonsmokers (85.5%), and those with ground-glass nodules (GGNs; 56.6%). EGFR mutation was not associated with recurrence and death in the entire cohort or GGN cohort. However, for patients with radiologic pure-solid appearance, EGFR mutation was an independent risk factor for RFS (aHR, 1.623; 95% CI, 1.192-2.210) and distant recurrence (aHR, 1.863; 95% CI, 1.311-2.650), but not OS. Subsequently, subgroup analysis based on EGFR mutation subtypes, including exon 19 deletions (19-Del), exon 21 L858R substitution (L858R), and rare mutations in patients with radiologic pure-solid appearance, revealed that all 3 subtypes have poorer RFS (19-Del: aHR, 1.424; 95% CI, 0.991-2.047; L858R: aHR, 1.708; 95% CI, 1.172-2.490; rare mutations: aHR, 2.500; 95% CI, 1.400-4.465) and higher prevalent distant recurrence (19-Del: aHR, 1.595; 95% CI, 1.061-2.400; L858R: aHR, 2.073; 95% CI, 1.371-3.140; rare mutations: aHR, 2.657; 95% CI, 1.397-5.050) compared with wild-type. In clinical stage I lung adenocarcinoma, EGFR mutation was associated with worse RFS and higher prevalent distant recurrence in patients with radiologic pure-solid appearance but not in patients with GGN.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study

To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Retrospective cohort study. Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate<15mL/min/1.73m2. AKI (defined as≥50% or≥0.3mg/dL serum creatinine increase). The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72mL/min/1.73m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. We lacked granular data, such as urine output. Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

102-LB: Cumulative Probability of Mortality among Non-Hispanic Black Compared with Non-Hispanic White Individuals with Type 2 Diabetes on Empagliflozin (EMPA-AA)—Real-World Data

Authors 1, 2 &amp; 11 participated equally. Given the underrepresentation of minorities in the CV outcome trials, guidelines encouraged investigating antihyperglycemic medications in minorities, particularly in non-Hispanic Blacks (Black). Our goal was to evaluate the incidence of all-cause mortality (ACM) among Black vs non-Hispanic White (White) patients with type 2 diabetes (T2D) who were prescribed empagliflozin (EMPA). We performed a multicenter retrospective study using EMR-derived data for adults with T2D cared for at 4 healthcare systems in North and South Carolina between Aug 2014 and Dec 2019. In patients without HF hospitalizations (hHF) prior to an initial EMPA prescription, we compared ACM in Black vs White patients. A propensity-score weighted analysis was performed to balance characteristics by race. The cumulative probability of ACM by race was estimated using the cumulative incidence function. A total of 8789 patients were eligible. Baseline characteristics and results are summarized in Table 1. After propensity-score weighted analysis adjusting for age, gender, and baseline comorbidities, there was no significant difference in the risk of ACM between Black vs White patients. In patients with T2D without hHF prior to an initial EMPA prescription, we found no significant difference in ACM in Black vs White patients. Disclosure B. M. Mishriky: Advisory Panel; Bayer Inc., Research Support; Lilly. A. Adams: None. W. Irish: Consultant; Eurofins Transplant Genomics, Other Relationship; CTI Clinical Trial and Consulting. D. M. Cummings: None. Y. Fu: None. J. Halladay: None. W. S. Jones: None. A. D. Boan: None. S. Jones berkeley: None. S. P. Patil: None. J. R. Powell: None. Funding Brody Brothers Endowment Fund (20-0922)