Fine-Gray Competing Risk Regression Research Articles

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Suicide among patients with oral cancer: A population-based study

BackgroundPatients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. MethodsSurveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. ResultsTotally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. ConclusionAs oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Favorable prostate-specific antigen levels correlate with a worse prognosis in high-grade prostate cancer: a population-based analysis.

To compare the association between prostate-specific antigen (PSA) levels and prostate cancer-specific mortality (PCSM), and the effectiveness of local treatment in patients with high-grade and low-grade prostate cancer (PCa). This retrospective cohort study enrolled patients diagnosed with clinically localized PCa (cT1-4N0M0) from January 2010 to December 2020 in the Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray competing risk regression analysis was conducted to generate cumulative incidence plots and estimate the hazards ratio (HR) and 95% confidence interval (95% CI) of PCSM. Multivariable restricted cubic spline (RCS) analysis was used to examine the non-linear associations of continuous values of PSA levels with PCSM. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics between different local treatment cohorts. A total of 392083 eligible patients were included in the study, including 327659 low-grade (Gleason score [GS]≤7) PCa and 64424 high-grade (GS≥8) PCa. In multivariate Fine-Gray competing risk regression analysis, using PSA levels of 4.1-10.0ng/ml as the reference, the adjusted HR among high-grade patients with PSA levels ≤2.5ng/ml, 2.6-4.0ng/ml, 10.1-20.0ng/ml and >20.0ng/ml were 1.988 (95% CI=1.677-2.358), 1.411 (95% CI=1.194-1.668), 1.472 (95% CI=1.351-1.603) and 2.506 (95% CI=2.318-2.709), respectively. Among low-grade PCa, the adjusted HR were 0.985 (95% CI=0.800-1.213), 0.727 (95% CI=0.602-0.877), 1.844 (95% CI=1.679-2.026) and 3.574 (95% CI=3.220-3.966), respectively. Multivariable-adjusted RCS analysis showed a U/J-shaped distribution relationship between PSA levels and PCSM in high-grade PCa, while there was a positive association between PSA levels and PCSM in low-grade PCa. As for local treatment effectiveness, radiation therapy (RT) provided better control of PCSM compared to radical prostatectomy (RP) and RP+RT in high-grade PCa, while RP provided better control of PCSM compared to RT and RP+RT in low-grade PCa. Low PSA level (≤2.5ng/ml) is significantly associated with very high risk of PCSM in high-grade localized PCa but not in low-grade localized PCa. High-grade localized PCa patients benefit more from RT in terms of PCSM control, while low-grade localized PCa patients benefit more from RP. High-grade localized PCa with low PSA level may be a unique subgroup that could benefit from novel risk stratification strategies in PCa, which requires further studies to investigate the potential of developing novel therapeutic strategies, prognostic tools, and clinical management approaches.

Concomitant use of lansoprazole and ceftriaxone is associated with an increased risk of ventricular arrhythmias and cardiac arrest in a large Japanese hospital database

To determine whether concomitant use of ceftriaxone and oral or intravenous lansoprazole increases the risk of ventricular arrhythmia and cardiac arrest in the real-world setting in Japan. The data analyzed were obtained from the JMDC hospital-based administrative claims database for the period April 2014 to August 2022. Patients who received a proton pump inhibitor (PPI) while receiving ceftriaxone or sulbactam/ampicillin were identified. The frequency of ventricular arrhythmia and cardiac arrest was analyzed according to whether oral or intravenous PPI was concomitant with ceftriaxone or sulbactam/ampicillin. Estimates of the incidence of ventricular arrhythmia and cardiac arrest were then compared among the groups, using the Fine-Gray competing risk regression model. The results showed that the risk of ventricular arrhythmia and cardiac arrest was significantly higher with concomitant ceftriaxone and oral lansoprazole (hazard ratio 2.92, 95% confidence interval 1.99-4.29, P<0.01) or intravenous lansoprazole (hazard ratio 4.57, 95% confidence interval 1.24-16.80, P=0.02) than with concomitant sulbactam/ampicillin and oral or intravenous lansoprazole. Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone.

Geriatric conditions and healthcare utilization among older adults living in subsidized housing.

Nearly 2.9 million older Americans with lower incomes live in subsidized housing. While regional and single-site studies show that this group has higher rates of healthcare utilization compared to older adults in the general community, little is known about healthcare utilization nationally nor associated risk factors. We conducted a retrospective cohort study of Medicare beneficiaries aged ≥65 enrolled in the National Health and Aging Trends Study in 2011, linked to Medicare claims data, including individuals living in subsidized housing and the general community. Participants were followed annually through 2020. Outcomes were hospitalization, short-term skilled nursing facility (SNF) utilization, long-term care utilization, and death. Fine-Gray competing risks regression analysis was used to assess the association of subsidized housing residence with hospitalization and nursing facility utilization, and Cox proportional hazards regression analysis was used to assess the association with death. Among 6294 participants (3600 women, 2694 men; mean age, 75.5 years [SD, 7.0]), 295 lived in subsidized housing at baseline and 5999 in the general community. Compared to older adults in the general community, those in subsidized housing had a higher adjusted subdistribution hazard ratio [sHR] of hospitalization (sHR 1.21; 95% CI, 1.03-1.43), short-term SNF utilization (sHR 1.49; 95% CI, 1.15-1.92), and long-term care utilization (sHR 2.72; 95% CI, 1.67-4.43), but similar hazard of death (HR, 0.86; 95% CI, 0.69-1.08). Individuals with functional impairment had a higher adjusted subdistribution hazard of hospitalization and short-term SNF utilization and individuals with dementia and functional impairment had a higher hazard of long-term care utilization. Older adults living in subsidized housing have higher hazards of hospitalization and nursing facility utilization compared to those in the general community. Housing-based interventions to optimize aging in place and mitigate risk of nursing facility utilization should consider risk factors including functional impairment and dementia.

Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P<0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths. Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.

Acute Kidney Injury and Subsequent Kidney Failure With Replacement Therapy Incidence in Older Adults With Advanced CKD: A Cohort Study of US Veterans

Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship. Retrospective cohort study. 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to2013. AKI, AKI severity, and age. KFRT and death. The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death. Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity. Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity. In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.

Later aorta operation after aortic valve replacement for bicuspid aortic valve

BackgroundWe investigated long-term outcomes, particularly later aorta operations and overall death in patients who underwent aortic valve replacement for bicuspid aortic valve without aortic surgery.MethodsBetween January 2002 and December 2022, 274 patients underwent aortic valve replacement for bicuspid aortic valve at our institution. Of them, 181 patients who did not undergo aortic surgery, in accordance with current guidelines, were analyzed retrospectively.ResultsThe median follow-up duration was 6.1 (2.0–10.6) years, and follow-up was completed in 97.8% of pateints. There were 3 patients (1.7%) who underwent later aorta operation during follow-up period. The cumulative later aorta operation rate at 10 years adjusting overall death as competing risk was 16.3%, and the estimated rates of freedom from overall death at 10 years was 83.7%. Fine-Gray competing risk regression model showed that aortic valve stenosis was only the predictor of later aorta operation (hazard ratio 8.477; p = 0.012). In multivariable Cox models, predictors of overall death were aortic valve stenosis (hazard ratio: 8.270, 95% confidence interval: 1.082–63.235; p = 0.042) and operation time (hazard ratio: 1.011, 95% confidence interval: 1.004–1.017; p = 0.002).ConclusionsPatients with bicuspid aortic valve with ascending aortic diameter less than 45 mm are at low risk of later aorta operation after isolated aortic valve replacement.

Association of multiparametric magnetic resonance imaging findings with oncologic outcomes in non-palpable localized prostate cancer.

281 Background: Multiparametric magnetic resonance imaging (mpMRI) is becoming increasingly integrated into the evaluation and medical decision making for localized prostate cancer. However, mpMRI findings have not been correlated with prostate cancer outcomes and therefore are not currently included in staging. The purpose of this study was to test the association between mpMRI detected extraprostatic extension with oncologic outcomes in patients with non-palpable prostate cancer. Methods: We used the Veterans Affairs Prostate Data Core to identify patients diagnosed with cT1N0M0 prostate cancer between 2000-2021 with an mpMRI prior to definitive treatment. We reviewed MRI reports to identify presence of extracapsular extension (MRI-T3a), seminal vesicle invasion (MRI-T3b), and adjacent organ invasion (MRI-T4). We assessed the impact of mpMRI findings on metastasis free survival with multivariable Fine-Gray competing-risks regression. Results: Overall, 3,142 veterans with cT1N0M0 prostate cancer were included. There were 1,411 (45%) Black patients. By clinical staging, 904 (29%) had low risk, 1,626 (52%) had intermediate risk, and 612 (19%) had high risk disease. The majority of patients were treated with radiation (N=2,267; 72%). There were 217 (7%) patients with MRI-T3a disease, 87 (3%) patients with MRI-T3b disease, and 26 (1%) patients with MRI-T4 disease. The median follow-up time was 5.4 years (90% CI, 1-13 years). The 5-year cumulative incidence of metastases for patients with low, intermediate, and high risk prostate cancer were 3% (95% CI, 2-4%), 7% (95% CI, 6-8%), and 15% (95% CI, 12-18%). The 5-year cumulative incidence of metastases for patients with MRI-T3a, MRI-T3b, and MRI-T4 disease were 15% (95% CI, 10-20%), 29% (95% CI, 29-39%), and 40% (95% CI, 13-66%). After controlling for age, race, risk stratification (which includes prostate specific antigen (PSA) and grade group), local therapy, and co-morbidities, the presence of MRI-T3a (HR 1.58, 95% CI 1.09-2.29, p=0.02), MRI-T3b (HR 3.38, 95% CI 2.31-4.95, p&lt;0.0001), and MRI-T4 disease (HR 4.47, 95% CI 2.32-8.62, p&lt;0.0001) were independently associated with worse metastasis free survival. Similar results were obtained with PSA and grade group as individual variables. Conclusions: Extraprostatic extension observed on mpMRI is independently prognostic of metastasis free survival in patients with non-palpable prostate cancer. mpMRI is a critical imaging modality that should be widely available for patients with prostate cancer, and studies are ongoing to define its role as a standard staging modality.

Competing risk nomogram predicting cause-specific mortality in older patients with testicular germ cell tumors.

Testicular germ cell tumor (TGCT) is the most common type of malignancy in young men, but rarely in older adults. We aimed to construct a competing risk model to predict the prognosis for older patients with TGCT. We collected TGCT patients aged 50 years or older diagnosed between 2004 and 2015 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. We estimated the cumulative incidences of cause-specific death (CSD) and other causes of death and established a nomogram predicting cause-specific mortality in older patients with TGCT by Fine-Gray competing risk regression. The concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC), and decision analysis curves (DCA) were used to evaluate the differentiation, accuracy, and clinical significance of the nomogram. A total of 2,751 older TGCT patients were included in the study. The 3-, 5-, and 10-year cumulative incidences were 4.4, 5.0 and 6.1%, respectively, for cause-specific death, and 3.8, 6.2, 13.1%, respectively, for other causes of death. Predictors of cause-specific mortality in older TGCT included age, marital status, annual household income, histology, tumor size, stage and surgery. In the training and validation sets, the C-indexes were greater than 0.8, indicating that the nomogram had good discrimination. The AUC revealed the same result. The calibration curves showed good agreement between the predicted and observed results of the nomogram. DCA curves indicated that the nomogram had more clinical significance than the conventional American Joint Committee on Cancer (AJCC) staging. Based on the total nomogram score of each case, all patients were categorized into low-risk and high-risk groups, and risk categorization allowed the identification of cases with a high risk of death. We established a competing risk nomogram with good performance that may help clinicians accurately predict the prognosis of older TGCT patients.

High blood pressure and colorectal cancer mortality in a 29-year follow-up of the Japanese general population: NIPPON DATA80.

Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980-2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30-49 years (hazard ratios 1.43 [95% confidence interval, 1.22-1.67] and 1.86 [1.32-2.62], respectively) but not in those aged 50-59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life.

Incidence and associated factors of developing second pelvic malignant neoplasms among prostate cancer patients treated with radiotherapy.

To identify risk factors of secondary pelvic malignant neoplasms (SPMNs) among prostate cancer (PCa) patients treated with radiotherapy. Simultaneously, population-based data were used to validate the high risk of SPMNs in PCa patients with radiotherapy. We identified male patients diagnosed with PCa (localized and regional) as the first primary cancer and pelvic malignant neoplasm (including bladder and rectal cancer) as secondary cancer from Surveillance, Epidemiology, and End Results database (1975-2020). An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Fine-Gray competing risk regression and Poisson regression were utilized to evaluate the risk of SPMNs development. Poisson regression was also performed to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to assess the overall survival (OS) of patients with SPMNs. 89397 PCa patients treated with radiotherapy were enrolled. We identified associated factors of SPMNs, including age at diagnosis, race, year of diagnosis, marital status, radiation strategy and latency. In the multivariable competing risk regression model and Poisson regression model, a significantly higher risk of SPMNs development was observed in patients over 50 years(P<0.05), white patients(P<0.001), unmarried patients and treated with brachytherapy combined with external beam radiotherapy or brachytherapy(P<0.05). Patients treated with radiotherapy had a higher bladder and rectal cancer incidence than the general population. Patients who developed SPMNs showed poorer OS. We identified several risk factors associated with SPMNs and confirmed a relatively higher incidence of bladder and rectal cancer among PCa patients with radiotherapy. These results help tailor treatment and surveillance strategies.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study

ImportanceThe use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DesignPopulation-based retrospective cohort study. ParticipantsPatients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. ExposureWarfarin use within 14 days of IE diagnosis. Main outcomes and measuresPatients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. ResultsThe matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39–0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70–1.53]), intracranial hemorrhage (HR:1.25 [0.77–2.04]), and gastrointestinal bleeding (HR:1.04 [0.60–1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34–8.31]), but not at 90-day (sub-HR:1.63 [0.95–2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Conclusions and relevanceWarfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Key pointsQuestion: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe?Findings: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding.Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

Baclofen and the risk of fall and fracture in older adults: A real-world cohort study.

The growth of oral muscle relaxant prescriptions among older adults in the United States is concerning due to the drugs' adverse sedative effects. Baclofen is a gamma-aminobutyric acid agonist muscle relaxant that is associated with encephalopathy. We characterized the risk of fall and fracture associated with oral baclofen against other muscle relaxants (tizanidine or cyclobenzaprine) in older adults. We designed a new-user, active-comparator study using tertiary health system data from Geisinger Health, Pennsylvania (January 2005 through December 2018). Older adults (aged ≥65 years) newly treated with baclofen, tizanidine, or cyclobenzaprine were included. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the treatment groups on 58 baseline characteristics. Fine-Gray competing risk regression was used to estimate the risk of fall and fracture. The study cohort comprised of 2205 new baclofen users, 1103 new tizanidine users, and 9708 new cyclobenzaprine users. During a median follow-up of 100 days, baclofen was associated with a higher risk of fall compared to tizanidine (IPTW incidence rate, 108.4 vs. 61.9 per 1000 person-years; subdistribution hazard ratio [SHR], 1.68 [95% CI, 1.20-2.36]). The risk of fall associated with baclofen was comparable to cyclobenzaprine (SHR, 1.17 [95% CI, 0.93-1.47]) with a median follow-up of 106 days. The risk of fracture was similar among patients treated with baclofen versus tizanidine (SHR, 0.85 [95% CI, 0.63-1.14]) or cyclobenzaprine (SHR, 0.85 [95% CI, 0.67-1.07]). The risk of fall associated with baclofen was greater than tizanidine, but not compared to cyclobenzaprine in older adults. The risk of fracture was comparable among the older users of baclofen, tizanidine, and cyclobenzaprine. Our findings may inform risk-benefit considerations in the increasingly common clinical encounters where oral muscle relaxants are prescribed.

Ratio of waist circumference to body mass index: A novel predictor of clinical outcome in hypertension patients.

We aim to investigate the influence of waist circumference and body mass index (BMI) on all-cause death and cardiovascular-specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all-cause mortality and cardiovascular events. The waist circumference-to-BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan-Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all-cause mortality. Subsequently, Fine-Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular-specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P<.05), while no significant difference was observed in waist circumference (P=.373). When analyzed as continuous, the risk of all-cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06-2.85). The restricted cubic spline illustrated an elevated risk of all-cause mortality as WtBR increased (J-shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular-specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all-cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity-related health.

Survival outcomes for lung neuroendocrine tumors in California differ by sociodemographic factors.

Lung neuroendocrine tumors (NETs) have few known predictors of survival. We investigated associations of sociodemographic, clinicopathologic, and treatment factors with overall survival (OS) and lung cancer-specific survival (LCSS) for incident lung NET cases (typical or atypical histology) in the California Cancer Registry (CCR) from 1992 to 2019. OS was estimated with the Kaplan-Meier method and compared by sociodemographic and disease factors univariately with the log-rank test. We used sequential Cox proportional hazards regression for multivariable OS analysis. LCSS was estimated using Fine-Gray competing risks regression. There were 6038 lung NET diagnoses (5569 typical, 469 atypical carcinoid); most were women (70%) and non-Hispanic White (73%). In our multivariable model, sociodemographic factors were independently associated with OS, with better survival for women (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.57-0.68, P < 0.001), married (HR 0.76, 95% CI 0.70-0.84, P < 0.001), and residents of high socioeconomic status (SES) neighborhoods (HRQ5vsQ1 0.73, 95% CI 0.62-0.85, P < 0.001). Compared to cases with private insurance, OS was worse for cases with Medicare (HR 1.24, 95% CI 1.10-1.40, P < 0.001) or Medicaid/other public insurance (HR 1.45, 95% CI 1.24-1.68, P < 0.001). In our univariate model, non-Hispanic Black Californians had worse OS than other racial/ethnic groups, but differences attenuated after adjusting for stage at diagnosis. In our LCSS models, we found similar associations between sex and marital status on survival, but no differences in outcomes by SES or insurance. By race/ethnicity, American Indian cases had worse LCSS. In summary, beyond disease-related and treatment variables, sociodemographic factors were independently associated with survival in lung NETs.

Association of race and ethnicity with pediatric burn outcomes: A population study of the Kids’ Inpatient Database

BackgroundWhile most studies on burn outcomes have focused on adults, it is unclear if the same socioeconomic and environmental inequalities affect paediatric patients. This study aims to investigate the impact of race and ethnicity on outcomes in paediatric burn patients. MethodsThe Kids' Inpatient Database is released by Agency for Healthcare Research and Quality, and is the largest publicly available database for the United States inpatient paediatric population. All paediatric burned patients in 2016 and 2019 were identified. Race and/or ethnicity was the primary exposure variable, and the primary outcome was a composite of several in-hospital morbidities. Secondary outcomes included death, non-routine disposition, and length of stay. Fine-Gray competing risks regression and multivariable logistic regression were used to analyze length of stay and all other outcomes, respectively. Analysis also isolated subgroups related to socioeconomic status and case severity. ResultsWe included12,582 pediatric burn patients in this study. No difference was found in composite morbidity between White patients and those of other race or ethnicity groups. Hispanic ethnicity was associated with longer lengths of stay and increased odds of routine (i.e. home) discharge. Black patients had increased length of stay compared to White patients only in severe burn cases. ConclusionsOur study implies that race- or ethnicity-associated mechanisms driving outcome disparities in adults does not necessarily apply in paediatric burn patients.

Recurrence After Complete Resection for Non-Small Cell Lung Cancer in the National Lung Screening Trial

BackgroundThe objective of this study was to evaluate patterns, predictors, and long-term outcomes of recurrent disease after complete resection for early-stage non-small cell lung cancer (NSCLC) using the National Lung Screening Trial (NLST). MethodsThe frequency of recurrence in patients with pathologic stage I-II NSCLC who underwent complete resection (lobectomy or bilobectomy) in the NLST was evaluated. Predictors of increased risk of recurrence were assessed by Fine-Gray competing risks regression. ResultsOf the 497 patients meeting study inclusion criteria, 94 experienced a recurrence—a rate of 4.9 (95% CI, 4.0-6.0) per 100 person-years. The 5-year cumulative incidence of recurrence was 20.1% (95% CI, 16.5%-23.9%). Most patients experienced recurrences at distant sites alone (n = 47 [50.0%]) or at both locoregional and distant sites (n = 30 [31.9%]). The median time from resection to recurrence was 18.8 (10.6-30.7) months. The incidence rate of recurrence was significantly lower among patients with lung cancer detected by low-dose computed tomography screening during one of the three screening rounds of the NLST when compared with patients with lung cancer detected by chest radiography screening and patients with lung cancer not detected by any form of screening (ie, those diagnosed after a negative or missed screening exam and those diagnosed during follow-up after the three screening rounds of the NLST were completed) (P < .001). Median survival (from the date of recurrence) of patients with pathologic stage I and stage II disease who had recurrences at locoregional, distant, or both sites was 63.0, 23.1, and 9.8 months and 28.9, 8.7, and 10.2 months, respectively. ConclusionsIn this analysis of NLST participants with completely resected stage I-II NSCLC, the 5-year cumulative incidence of recurrence was 20%. Nearly 82% of recurrences were at distant sites and associated with poor survival.

Advanced chronic kidney disease; A comparison between nephroureterectomy and nephron-sparing surgery for upper tract urothelial carcinoma.

Renal function outcomes between radical nephroureterectomy (RNU) and nephron-sparing surgery (NSS) for upper tract urothelial carcinoma (UTUC) patients are not well established. We sought to compare the incidence and factors associated with development of advanced chronic kidney disease (CKD) between RNU and NSS and examine the role of acute kidney injury (AKI) on renal function outcomes. We retrospectively analyzed an institutional database for patients who underwent either RNU or NSS for UTUC. Cumulative incidence of postoperative advanced CKD, defined as eGFR < 30 ml/min/1.73 m2, was compared between groups. Fine-Gray competing risk regression was used to identify predictors of advanced CKD. Locally weight scatterplot smoothing was used to assess postoperative eGFR trends. AKI events were counted, staged, and assessed for influence of progression to advanced CKD. Four hundred and twenty-six patients were included in analysis, with a median follow up of 6.68 years (IQR 3.4-12.2). Median preoperative eGFR was similar between the groups (NSS: 68 ml/min/1.73 m2, RNU: 65 ml/min/1.73 m2,P = 0.220). Cumulative incidence of advanced CKD was significantly lower in the NSS cohort (P = 0.009). Factors associated with advanced CKD included age, diabetes, recurrent AKI and RNU. Percent of patients with an AKI event differed between the groups (51.5% NSS, 72.7% RNU, P = <0.001), there was no between group difference in percentage of patients with recurrent AKI (25.6% NSS, 25.9% RNU, P =1). NSS provides a renal function benefit in UTUC. AKI is common among UTUC patients and recurrent AKI is a risk factor for development of advanced CKD.

Donor-Specific HLA Antibodies Are Associated with Graft Failure and Delayed Hematologic Recovery after Unrelated Donor Hematopoietic Cell Transplantation

Graft failure (GF) is one of the major concerns after allogeneic hematopoietic cell transplantation (allo-HCT) and remains a significant cause of morbidity and mortality. Although earlier reports have associated the presence of donor-specific HLA antibodies (DSAs) with increased risk of GF after unrelated donor allo-HCT, recent studies have failed to confirm this association. We sought to validate the presence of DSAs as a risk factor for GF and hematologic recovery in the unrelated donor allo-HCT setting. We retrospectively evaluated 303 consecutive patients who underwent their first unrelated donor allo-HCT at our institution from January 2008 to December 2017. DSA evaluation was performed using 2 Single Antigen Beads (SAB) assays, DSA titration with 1:2, 1:8, and 1:32 dilutions, C1q-binding assay, and absorption/elution protocol to assess possible false-positive DSA reactivity. The primary endpoints were neutrophil and platelet recovery and GF, whereas the secondary endpoint was overall survival. Multivariable analyses were performed using Fine-Gray competing risks regression or Cox proportional hazards regression models. The median patient age was 14 years (range, 0-61 years), 56.1% were male, and 52.5% were transplanted for nonmalignant diseases. Eleven patients (3.63%) were DSA-positive. Of them, 10 had preexisting DSAs, and one showed post-transplant de novo DSA. Nine patients had 1 DSA, 1 had 2 DSAs, and 1 had 3 DSAs, with a median MFI of 4334 (range, 588-20,456) and 3581 (range, 227-12,266) in LABScreen and LIFECODES SAB assays, respectively. Overall, 21 patients experienced GF. Of them, 12 had primary graft rejection, 8 had secondary graft rejection, and 1 had primary poor graft function. The cumulative incidences of GF at 28, 100, and 365 days were 4.0% (95% CI, 2.2%-6.6%), 6.6% (95% CI, 4.2%-9.8%), and 6.9% (95% CI, 4.4%-10.2%), respectively. In the multivariable analyses, DSA-positive patients had significantly delayed neutrophil (subdistribution hazard ratio [SHR] = 0.48; 95% CI, 0.29-0.81; P = .006) and platelet recovery (SHR = 0.51; 95% CI, 0.35-0.74; P = .0003) than patients without DSAs. In addition, only DSAs were significant predictors of primary GF at 28 days (SHR = 2.78; 95% CI, 1.65-4.68; P = .0001). The Fine-Gray regression also demonstrated that the presence of DSAs was strongly associated with a higher incidence of overall GF (SHR = 7.60; 95%CI, 2.61-22.14; P = .0002). DSA-positive patients with GF had significantly higher median MFI values than DSA-positive patients who achieved engraftment in LIFECODES SAB assay using neat serum (10,334 vs. 1250; P = .006) and in LABScreen SAB at 1:32 dilution (1627 vs. 61; P = .006). All 3 patients with C1q-positive DSAs failed to engraft. DSAs were not predictive of inferior survival (hazard ratio = 0.50; 95% CI, 0.20-1.26, P = .14). Our results validate the presence of DSAs as a significant risk factor for GF and poor hematologic recovery after unrelated donor allo-HCT. Thus, careful pre-transplant DSA evaluation may optimize unrelated donor selection and improve allo-HCT outcomes.