First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia.

BACKGROUND: First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth. OBJECTIVE: The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia. STUDY DESIGN: This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios. RESULTS: The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001). CONCLUSION: In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Competitive Risk Analysis of Prognosis in Older Adults with Sigmoid Colon Adenocarcinoma: A Population-Based Study.

BACKGROUND: The purpose of this study is to employ a competing risk model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for elderly individuals with sigmoid colon adenocarcinoma (SCA) and compare them with the classic Cox proportional hazards model. METHODS: We extracted data from elderly patients diagnosed with SCA registered in the SEER database between 2010 and 2015. Univariate analysis was conducted using cumulative incidence functions and Gray's test, while multivariate analysis was performed using both the Fine-Gray and Cox proportional hazards models. RESULTS: Among the 10,712 eligible elderly patients diagnosed with SCA, 5595 individuals passed away: 2987 due to sigmoid colon adenocarcinoma and 2608 from other causes. The results of one-way Gray's test showed that age, race, marital status, AJCC stage, differentiation grade, tumor size, surgical status, liver metastasis status, lung metastasis status, brain metastasis status, radiotherapy status, and chemotherapy status all affected the prognosis of SCA (P < .05). Multivariate analysis showed that sex, age, race, marital status, and surgical status affected the prognosis of SCA (P < .05). Multifactorial Fine-Gray analysis revealed that key factors influencing the prognosis of SCA patients include age, race, marital status, AJCC stage, grade classification, surgical status, tumor size, liver metastasis, lung metastasis, and chemotherapy status (P < .05). CONCLUSION: Data from the SEER database were used to more accurately estimate CIFs for sigmoid colon adenocarcinoma-specific mortality and prognostic factors using competing risk models.

First-trimester prediction of preterm pre-eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth.

OBJECTIVE: To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. DESIGN: Secondary analysis of data from the SPREE study and the ASPRE trial. SETTING: Multicentre studies. POPULATION: In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. METHODS: Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. MAIN OUTCOME MEASURE: Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). RESULTS: Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. CONCLUSION: Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

Screening for pre-eclampsia with competing-risks model using placental growth factor measurement in blood samples collected before 11 weeks' gestation.

OBJECTIVES: To describe the distributional properties and assess the performance of placental growth factor (PlGF) measured in blood samples collected before 11 weeks' gestation in the prediction of pre-eclampsia (PE). METHODS: The study population consisted of pregnant women included in the Pre-eclampsia Screening in Denmark (PRESIDE) study with a PlGF measurement from the routine combined first-trimester screening (cFTS) blood sample collected at 8-14 weeks' gestation. PRESIDE was a prospective multicenter study investigating the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for PE in a Danish population. In the current study, serum concentration of PlGF in the cFTS blood samples was analyzed in batches between January and June 2021. RESULTS: A total of 8386 pregnant women were included. The incidence of PE was 0.7% at < 37 weeks' gestation and 3.0% at ≥ 37 weeks. In blood samples collected at 10 weeks' gestation, PlGF multiples of the median (MoM) were significantly lower in pregnancies with preterm PE < 37 weeks compared to unaffected pregnancies. However, PlGF MoM did not differ significantly between pregnancies with PE and unaffected pregnancies in samples collected before 10 weeks' gestation. CONCLUSIONS: The gestational-age range for PlGF sampling may be expanded from 11-14 to 10-14 weeks when assessing the risk for PE using the FMF first-trimester screening model. There is little evidence to support the use of PlGF in blood samples collected before 10 weeks' gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of different methods of first-trimester screening for preterm pre-eclampsia: cohort study.

OBJECTIVE: To compare the predictive performance of three different mathematical models for first-trimester screening of pre-eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk-scoring systems. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non-malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing-risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen-positive rate (SPR), as well as the area under the receiver-operating-characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6-95.8%), 73.8% (95% CI, 58.7-88.9%) and 79.8% (95% CI, 66.1-93.5%) of early PE; 72.7% (95% CI, 62.9-82.6%), 69.2% (95% CI, 58.8-79.6%) and 74.1% (95% CI, 64.2-83.9%) of preterm PE; and 55.1% (95% CI, 48.8-61.4%), 47.1% (95% CI, 40.6-53.5%) and 53.9% (95% CI, 47.4-60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879-0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3-58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4-76.4%) of preterm PE at 33.8% SPR. CONCLUSIONS: The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of screening performance of first-trimester competing-risks prediction model for small-for-gestational age in Asian population.

OBJECTIVE: To examine the external validity of the Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at 11-14 weeks' gestation in an Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 120 women with a singleton pregnancy undergoing routine assessment at 11-14 weeks' gestation. We applied the FMF competing-risks model for the first-trimester prediction of SGA, combining maternal characteristics and medical history with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) concentration. We calculated risks for different cut-offs of birth-weight percentile (< 10th , < 5th or < 3rd percentile) and gestational age at delivery (< 37 weeks (preterm SGA) or SGA at any gestational age). Predictive performance was examined in terms of discrimination and calibration. RESULTS: The predictive performance of the competing-risks model for SGA was similar to that reported in the original FMF study. Specifically, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA with birth weight < 10th percentile (SGA < 10th ) and preterm SGA with birth weight < 5th percentile (SGA < 5th ), with areas under the receiver-operating-characteristics curve (AUCs) of 0.765 (95% CI, 0.720-0.809) and 0.789 (95% CI, 0.736-0.841), respectively. Combining maternal factors with MAP and PlGF yielded the best model for predicting preterm SGA with birth weight < 3rd percentile (SGA < 3rd ) (AUC, 0.797 (95% CI, 0.744-0.850)). After excluding cases with pre-eclampsia, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA < 10th and preterm SGA < 5th , with AUCs of 0.743 (95% CI, 0.691-0.795) and 0.762 (95% CI, 0.700-0.824), respectively. However, the best model for predicting preterm SGA < 3rd without pre-eclampsia was the combination of maternal factors and PlGF (AUC, 0.786 (95% CI, 0.723-0.849)). The FMF competing-risks model including maternal factors, MAP, UtA-PI and PlGF achieved detection rates of 42.2%, 47.3% and 48.1%, at a fixed false-positive rate of 10%, for the prediction of preterm SGA < 10th , preterm SGA < 5th and preterm SGA < 3rd , respectively. The calibration of the model was satisfactory. CONCLUSION: The screening performance of the FMF first-trimester competing-risks model for SGA in a large, independent cohort of Asian women is comparable with that reported in the original FMF study in a mixed European population. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

One-shot distributed algorithms for addressing heterogeneity in competing risks data across clinical sites.

OBJECTIVE: To characterize the interplay between multiple medical conditions across sites and account for the heterogeneity in patient population characteristics across sites within a distributed research network, we develop a one-shot algorithm that can efficiently utilize summary-level data from various institutions. By applying our proposed algorithm to a large pediatric cohort across four national Children's hospitals, we replicated a recently published prospective cohort, the RISK study, and quantified the impact of the risk factors associated with the penetrating or stricturing behaviors of pediatric Crohn's disease (PCD). METHODS: In this study, we introduce the ODACoRH algorithm, a one-shot distributed algorithm designed for the competing risks model with heterogeneity. Our approach considers the variability in baseline hazard functions of multiple endpoints of interest across different sites. To accomplish this, we build a surrogate likelihood function by combining patient-level data from the local site with aggregated data from other external sites. We validated our method through extensive simulation studies and replication of the RISK study to investigate the impact of risk factors on the PCD for adolescents and children from four children's hospitals within the PEDSnet, A National Pediatric Learning Health System. To evaluate our ODACoRH algorithm, we compared results from the ODACoRH algorithms with those from meta-analysis as well as those derived from the pooled data. RESULTS: The ODACoRH algorithm had the smallest relative bias to the gold standard method (-0.2%), outperforming the meta-analysis method (-11.4%). In the PCD association study, the estimated subdistribution hazard ratios obtained through the ODACoRH algorithms are identical on par with the results derived from pooled data, which demonstrates the high reliability of our federated learning algorithms. From a clinical standpoint, the identified risk factors for PCD align well with the RISK study published in the Lancet in 2017 and other published studies, supporting the validity of our findings. CONCLUSION: With the ODACoRH algorithm, we demonstrate the capability of effectively integrating data from multiple sites in a decentralized data setting while accounting for between-site heterogeneity. Importantly, our study reveals several crucial clinical risk factors for PCD that merit further investigations.

Survival and disease burden analyses of occupational pneumoconiosis during 1958-2021 in Huangshi city, China: a retrospective cohort study.

BACKGROUND: Pneumoconiosis, a chronic disease stemming from prolonged inhalation of dust particles, stands as a significant global burden of occupational diseases. This study aims to investigate the survival outcomes of pneumoconiosis patients in Huangshi city, China, while also evaluating the disease burden on afflicted patients. METHODS: Data for this study were sourced from the Huangshi Center for Disease Control and Prevention. Survival analyses of pneumoconiosis patients were conducted employing life tables and the Kaplan-Meier method. The Cox proportional hazards models were deployed to identify factors influencing pneumoconiosis patients' survival duration. Competing risks models were employed to confirm the validity of the model outcomes. Additionally, in the disease burden assessment, disability-adjusted life years (DALYs) were computed for various demographic groups and time frames. RESULTS: A total of 5,641 pneumoconiosis cases, diagnosed in Huangshi City, Hubei Province between 1958 and 2021, were incorporated into the cohort analysis. The probability of mortality and the risk ratio increased with advancing age. Notably, the median survival time of stage III pneumoconiosis patients was significantly shorter compared with those in stages I and II. The Cox proportional hazards model and competing risks analyses underscored several significant factors influencing survival time, including dust exposure duration (HR = 1.197, 95% CI: 1.104-1.298), age at first diagnosis (HR = 3.149, 95% CI: 2.961-3.349), presence of silicosis (HR = 1.378, 95% CI: 1.254-1.515), and stage II-III pneumoconiosis (HR = 1.456, 95% CI: 1.148-1.848). Cumulatively, DALYs amounted to 7,974.35 person-years, with an average of 1.41 person-years. The period between 2000 and 2019 witnessed the highest disease burden. CONCLUSION: Our findings highlight the urgent need for improved prevention, earlier detection, and more effective management strategies for the occupational pneumoconiosis population. This study not only underscores the persistent issue of pneumoconiosis in industrial environments but also serves as a crucial call to action for policymakers and healthcare providers.

Competing-risks analysis for evaluating the prognosis of patients with microinvasive cutaneous squamous cell carcinoma based on the SEER database.

BACKGROUND: Utilizing the traditional Cox regression model to identify the factors affecting the risk of mortality due to microinvasive cutaneous squamous cell carcinoma (micSCC) may produce skewed results. Since cause-specific mortality can guide clinical decision-making, this study employed the Fine-Gray model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify significant predictive variables for the risk of micSCC-related mortality. METHODS: This study used the information of patients with micSCC who were listed in the SEER database during 2000-2015. Cox regression and Fine-Gray models were utilized for the multivariable analysis, and Gray's test and the cumulative incidence function were used for the univariable analyses. RESULTS: There were 100 patients who died from other reasons and 38 who died from micSCC among the 1259 qualified patients with micSCC. Most were female, white, married, had localized metastasis, etc. According to the univariable Gray's test (P < 0.05), the cumulative incidence rate for events of interest was strongly associated with age, sex, marital status, American Joint Committee on Cancer staging, radiation status, summary stage, chemotherapy status, surgery status, and tumor size. Multivariable Cox regression analysis and multivariable competing-risks analysis indicated that age, tumor size, and income were independent risk variables for the prognosis of patients with micSCC. In both age and tumor size variables, the competing-risks model showed a slight decrease in the hazard ratio and a slight narrowing of the 95% confidence interval compared with the Cox regression model. However, this pattern is not evident in the income variable. CONCLUSIONS: This study established a Fine-Gray model for identifying the independent risk factors that influence the risk of mortality among patients with micSCC. This study uncovers that, in the context of competing risks, age, tumor size, and income serve as independent risk factors influencing the risk of mortality due to micSCC among patients. Our findings have the potential to provide more accurate risk assessments for patient outcomes and contribute to the development of individualized treatment plans.

Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre-eclampsia.

OBJECTIVE: To examine the effect of self-declared race on serum placental growth factor (PlGF) and sFlt-1/PlGF ratio and the impact on pre-eclampsia (PE) prediction. DESIGN: Prospective observational study. SETTING: Two UK maternity hospitals. POPULATION: 29 035 women with singleton pregnancies attending a routine 35+0 to 36+6 weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE. METHODS: The predictive performance of PlGF and sFlt-1/PlGF for PE in minority racial groups (versus white) was examined. MAIN OUTCOME MEASURE: Delivery with PE. RESULTS: Compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut-off corresponding to a screen-positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut-off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut-off in sFlt-1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient-specific risks. CONCLUSION: Screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.

Incidence of pre-eclampsia: effect of deprivation.

OBJECTIVES: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of pre-eclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the 'history-only' competing-risks model (based on maternal characteristics and medical history). METHODS: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criteria were delivery at ≥ 24 weeks' gestation of babies without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history, which was then reviewed by a doctor together with the woman. Patients were asked to self-identify as white, black, South Asian, East Asian or mixed race. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to their level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. IMD was assigned based on a woman's postcode. Risk factors for PE and its incidence were assessed across IMD using chi-square test or t-test, as appropriate. The relationship between IMD and gestational age at delivery with PE was evaluated by fitting parametric survival models for IMD alone, IMD combined with race and IMD combined with the Fetal Medicine Foundation history-only competing-risks model. RESULTS: The incidence of PE (n = 4088, 2.6%) increased progressively across IMD quintiles, from 2.0% in Quintile 5 (least deprived) to 3.0% in Quintile 1 (most deprived). Compared with white women and those in other racial groups, black women had a higher incidence of PE (4.8%), were less often in IMD Quintiles 4 and 5, and were more often in IMD Quintiles 1 and 2. None of the IMD quintiles improved the prediction of PE compared with that provided by the history-only competing-risks model (which includes race). The history-only competing-risks model with vs without IMD had a similar detection rate for delivery with PE at < 37 weeks' gestation (44.1% (95% CI, 41.1-47.2%) vs 43.9% (95% CI, 40.1-47.0%)) and at any gestational age (35.2% (95% CI, 33.8-36.7%) vs 35.1% (95% CI, 33.7-36.6%)), at a 10% screen-positive rate. CONCLUSIONS: The incidence of PE is higher in women living in the most deprived areas in South East England and in black women (vs those of other racial groups), who also live in areas of higher deprivation. However, in screening for PE, inclusion of IMD does not improve the prediction of PE provided by race and other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of first-trimester combined screening for preterm pre-eclampsia: findings from cohort of 10 110 pregnancies in Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing-risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11-13 weeks' gestation of preterm pre-eclampsia (PE) in a Spanish population. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non-malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient-specific risks for term and preterm PE were calculated according to the FMF competing-risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen-positive rate (SPR). Risk calibration of the model was assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA-PI MoM were significantly higher, and median serum PlGF MoM and PAPP-A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA-PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9-82.6%). An alternative strategy of replacing PlGF with PAPP-A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8-77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). CONCLUSIONS: The FMF model is effective in predicting preterm PE in the Spanish population at 11-13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high-quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of maternal serum glycosylated fibronectin (GlyFn), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). METHODS: This was a case-control study in which maternal serum GlyFn was measured using a point-of-care device in stored samples from a non-intervention screening study of singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. In the same samples, PlGF was measured by time-resolved fluorometry. We used samples from women who delivered with PE at < 37 weeks' gestation (n = 100), PE at ≥ 37 weeks (n = 100), gestational hypertension (GH) at < 37 weeks (n = 100), GH at ≥ 37 weeks (n = 100) and 1000 normotensive controls with no pregnancy complications. In all cases, MAP and UtA-PI had been measured during the routine 11-13-week visit. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements of medical history. Similarly, the measured values of MAP, UtA-PI and PlGF were converted to MoMs. The competing-risks model was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE or GH at < 37 and ≥ 37 weeks' gestation. Screening performance was estimated by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at 10% fixed false-positive rate (FPR). RESULTS: The maternal characteristics and elements of medical history with a significant effect on the measurement of GlyFn were maternal age, weight, height, race, smoking status and history of PE. In pregnancies that developed PE, GlyFn MoM was increased and the deviation from normal decreased with increasing gestational age at delivery. The DR and AUC of screening for delivery with PE at < 37 weeks' gestation by maternal factors alone were 50% and 0.834, respectively, and these increased to 80% and 0.949, respectively, when maternal risk factors were combined with MAP, UtA-PI and PlGF (triple test). The performance of the triple test was similar to that of screening by a combination of maternal factors, MAP, UtA-PI and GlyFn (DR, 79%; AUC, 0.946) and that of screening by a combination of maternal factors, MAP, PlGF and GlyFn (DR, 81%; AUC, 0.932). The performance of screening for delivery with PE at ≥ 37 weeks' gestation was poor; the DR for screening by maternal factors alone was 35% and increased to only 39% with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. The DR of screening for GH with delivery at < 37 and ≥ 37 weeks' gestation by maternal factors alone was 34% and 25%, respectively, and increased to 54% and 31%, respectively, with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. CONCLUSIONS: GlyFn is a potentially useful biomarker in first-trimester screening for preterm PE, but the findings of this case-control study need to be validated by prospective screening studies. The performance of screening for term PE or GH at 11 + 0 to 13 + 6 weeks' gestation by any combination of biomarkers is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of adverse perinatal outcome at midgestation.

OBJECTIVES: First, to investigate the association between adverse neonatal outcomes and birth weight and gestational age at delivery. Second, to describe the distribution of adverse neonatal outcomes within different risk strata derived by a population stratification scheme based on the midgestation risk assessment for small-for-gestational-age (SGA) neonates using a competing-risks model. METHODS: This was a prospective observational cohort study in women with a singleton pregnancy attending a routine hospital visit at 19 + 0 to 23 + 6 weeks' gestation. The incidence of neonatal unit (NNU) admission for ≥ 48 h was evaluated within different birth-weight-percentile subgroups. The pregnancy-specific risk of delivery with SGA < 10th percentile at < 37 weeks was estimated by the competing-risks model for SGA, combining maternal factors and the likelihood functions of Z-score of sonographically estimated fetal weight and uterine artery pulsatility index multiples of the median. The population was stratified into six risk categories: > 1 in 4, > 1 in 10 to ≤ 1 in 4, > 1 in 30 to ≤ 1 in 10, > 1 in 50 to ≤ 1 in 30, > 1 in 100 to ≤ 1 in 50 and ≤ 1 in 100. The outcome measures were admission to the NNU for a minimum of 48 h, perinatal death and major neonatal morbidity. The incidence of each adverse outcome was estimated in each risk stratum. RESULTS: In the study population of 40 241 women, 0.8%, 2.5%, 10.8%, 10.2%, 19.0% and 56.7% were in the risk strata > 1 in 4, > 1 in 10 to ≤ 1 in 4, > 1 in 30 to ≤ 1 in 10, > 1 in 50 to ≤ 1 in 30, > 1 in 100 to ≤ 1 in 50 and ≤ 1 in 100, respectively. Women in higher-risk strata were more likely to deliver a baby that suffered an adverse outcome. The incidence of NNU admission for ≥ 48 h was highest in the > 1 in 4 risk stratum (31.9% (95% CI, 26.9-36.9%)) and it gradually decreased until the ≤ 1 in 100 risk stratum (5.6% (95% CI, 5.3-5.9%)). The mean gestational age at delivery in SGA cases with NNU admission for ≥ 48 h was 32.9 (95% CI, 32.2-33.7) weeks for risk stratum > 1 in 4 and progressively increased to 37.5 (95% CI, 36.8-38.2) weeks for risk stratum ≤ 1 in 100. The incidence of NNU admission for ≥ 48 h was highest for neonates with birth weight below the 1st percentile (25.7% (95% CI, 23.0-28.5%)) and decreased progressively until the 25th to < 75th percentile interval (5.4% (95% CI, 5.1-5.7%)). Preterm SGA neonates < 10th percentile had significantly higher incidence of NNU admission for ≥ 48 h compared with preterm non-SGA neonates (48.7% (95% CI, 45.0-52.4%) vs 40.9% (95% CI, 38.5-43.3%); P < 0.001). Similarly, term SGA neonates < 10th percentile had significantly higher incidence of NNU admission for ≥ 48 h compared with term non-SGA neonates (5.8% (95% CI, 5.1-6.5%) vs 4.2% (95% CI, 4.0-4.4%); P < 0.001). CONCLUSIONS: Birth weight has a continuous association with the incidence of adverse neonatal outcomes, which is affected by gestational age. Pregnancies at high risk of SGA, estimated at midgestation, are also at increased risk for adverse neonatal outcomes. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing-risks model.

OBJECTIVE: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt-1/PlGF ratio (> 90th percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt-1 ('double test') or PlGF, sFlt-1 and MAP ('triple test'). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests. RESULTS: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7-23.0%) and 12.4% (9.7-15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9-26.8%) and 12.9% (7.7-17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4-21.6%) and 5.4% (0.0-10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. CONCLUSION: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

How socioeconomic and clinical factors impact prostate-cancer-specific and other-cause mortality in prostate cancer stratified by clinical stage: Competing-risk analysis.

BACKGROUND: The aim of this study was to analyze the causes of death and risk factors of prostate-cancer-specific mortality (PCSM) and other-cause mortality (OCM) at different clinical stages using data from the Surveillance, Epidemiology, and End Results database. METHODS: The characteristics and cause-specific death classifications of males with prostate cancer (PCa) were extracted. Multivariate competing-risk regression analysis was used to identify significant predictors and quantify the cumulative incidence of PCSM and OCM at different clinical stages. RESULTS: Of the 244,433 PCa patients who were included, 19,274 died from 7356 PCSM, and 11,918 from OCM. The proportion of PCSM gradually increased from 2010 to 2016. The risk factors for PCSM in the localized PCa stage included older age, not being married, living in a county with higher poverty rates, and higher PSA levels and Gleason scores. Meanwhile, Medicaid and lower education levels were the additional risk factors of OCM. The risk factors for PCSM in the regional PCa stage included older age, not being married, Medicaid, living in a county with higher poverty rates, and higher PSA levels and Gleason scores. Meanwhile, the income level did not affect OCM risk. The risk factors for PCSM in the distant metastatic PCa stage included a separated/divorced/widowed marital status, Medicaid, and higher PSA levels and Gleason scores. Meanwhile, older age, an unmarried or separated/divorced/widowed marital status, and higher PSA levels were risk factors for OCM. In addition, receiving both surgery and radiation was worse than just receiving surgery for PCa specific survival in localized and regional PCa patients. CONCLUSION: Some pretreatment and treatment factors may influence OCM that are not identical to those for PCSM at the corresponding stage. Decision-makers and managers should fully consider OCM to maximize treatment benefits for PCa.