Flexible Parametric Survival Models Research Articles

Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study.

Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES). Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common cancers. Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years (95% CI: 2.5-3.2 years) vs. 1.6 years (95% CI: 1.3-1.9 years)] and breast cancer [1.6 years (95% CI: 1.4-1.8 years) vs. 1.2 years (95% CI: 1.0-1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years (95% CI: 16.1-16.8 years) vs. 16.2 years (95% CI: 15.7-16.7 years)] and liver cancer [15.5 years (95% CI: 15.0-16.0 years) vs. 14.7 years (95% CI: 14.0-15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years (95% CI: 0.4-1.4 years) vs. 0.6 years (95% CI: 0.2-1.0 years)] or melanoma [0.9 years (95% CI: 0.8-1.1 years) vs. 0.7 years (95% CI: 0.5-0.8 years)] had the lowest average LOLE. Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expectancy.

Examining the effects of social assistance on suicide-related behaviour among impoverished older adults in Korea using a nationwide cohort study from 2010–2019

Suicide rates among older adults in Korea are one of the highest in the world. Although prior research found that poverty is associated with suicide mortality among older adults in Korea, it is unknown whether being a recipient of social assistance may reduce suicide risk among older adults living in poverty. We examined the impact of the public assistance program on suicide-related behaviour (SRB). Data from a nationwide cohort in the Korean National Health Insurance Database, including demographic and medical treatment information, linked to the vital statistics for 2010–19 was used. The entire Korean population born before 1951 was included (n = 7,889,086). Flexible parametric survival model was performed to assess whether the risk of SRB hospitalisation and death differed across a) different levels of socioeconomic status, and b) social assistance status among the poor, using gender-stratified models. Older age, chronic disease, poverty, and being out of the labour market were associated with higher SRB hospitalisation and death for both genders. Among those living in poverty, social assistance recipients had lower rates for SRB death and hospitalisation, compared to the low-income non-recipients. Men who were non-recipients had 0.21 higher hazards ratio (95%CI 0.20 to 0.22) for SRB deaths compared to recipients, and the difference was 0.11 (95%CI 0.10 to 0.11) in women, with similar patterns for SRB hospitalizations. Poverty was associated with higher SRB death and hospitalisation among older adults in Korea. Social assistance targeting the older population may help reduce SRB.

Early-Life Disease Exposure and Its Heterogeneous Effects on Mortality Throughout Life: Sweden, 1905-2016.

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905-1929 from age 1 until age 85. We measure exposure to disease using the local post-early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1-85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects.

Excess Mortality and Loss of Life Expectancy After Myocardial Infarction: A Registry-Based Matched Cohort Study.

The effect of myocardial infarction (MI) on life expectancy is difficult to study because the prevalence of MI hinders direct comparison with the life expectancy of the general population. We sought to assess this in relation to age, sex, and left ventricular ejection fraction (LVEF) by comparing individuals with MI with matched comparators without previous MI. We included patients with a first MI between 1991 and 2022 from the nationwide SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), each matched with up to 5 comparators on age, sex, and region of residence. Flexible parametric survival models were used to estimate excess mortality risk and mean loss of life expectancy (LOLE) depending on index year, age, sex, and LVEF, and adjusted for differences in characteristics. A total of 335 748 cases were matched to 1 625 396 comparators. A higher LOLE was observed in younger individuals, women, and those with reduced LVEF (<50%). In 2022, the unadjusted and adjusted mean LOLE spanned from 11.1 and 9.5 years in 50-year-old women with reduced LVEF to 5 and 3.7 months in 80-year-old men with preserved LVEF. Between 1992 and 2022, the adjusted mean LOLE decreased by 36% to 55%: from 4.4 to 2.0 years and from 3.3 to 1.9 years in 50-year-old women and men, respectively, and from 1.7 to 1.0 years and from 1.4 to 0.9 years in 80-year-old women and men, respectively. LOLE is higher in younger individuals, women, and those with reduced LVEF, but is attenuated when adjusting for comorbidities and risk factors. Advances in MI treatment during the past 30 years have almost halved LOLE, with no clear sign of leveling off to a plateau.

Survival outcomes after breast cancer surgery among older women with early invasive breast cancer in England: population-based cohort study.

This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer. Women aged over 50 years with early invasive breast cancer diagnosed in England (2014-2019) who had breast surgery were identified from Cancer Registry data. Survival estimates were calculated from a flexible parametric survival model. A competing risk approach was used for breast cancer-specific survival (BCSS). Standardized survival probabilities and cumulative incidence functions for breast cancer death were calculated for each treatment by age. Among 101 654 women, 72.2% received BCS + RT and 27.8% received mastectomy. Age, co-morbidity and frailty were associated with overall survival (OS), but only age and co-morbidity were associated with BCSS. Survival probabilities for OS were greater for BCS + RT (90.3%) versus mastectomy (87.0%), and the difference between treatments varied by age (50 years: 1.9% versus 80 years: 6.5%). Cumulative incidence functions for breast cancer death were higher after mastectomy (5.1%) versus BCS + RT (3.9%), but there was little change in the difference by age (50 years: 0.9% versus 80 years: 1.2%). The results highlight the change in baseline mortality risk by age for OS compared to the stable baseline for BCSS. For OS, the difference in survival probabilities for BCS + RT and mastectomy increased slightly with age. The difference in cumulative incidence functions for breast cancer death by surgery type was small regardless of age. Evidence on real-world survival outcomes among older populations with breast cancer is informative for treatment decision-making.

Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults

PurposeWe investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths. MethodsWe analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17–39 years at baseline in 1963–2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975–1985, ≥1985 and women: <1985, 1985–1994, ≥1995). ResultsComparing men with obesity vs. normal weight, all-cause and “other-cause” mortality associations decreased over periods; HR (95% CI) 1.92 (1.83–2.01) and 1.70 (1.58–1.82) for all-cause and 1.72 (1.58–1.87) and 1.40 (1.28–1.53) for “other-cause” mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51–2.94) and 3.91 (3.37–4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women. ConclusionsAccounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

Discrimination of the Veterans Aging Cohort Study Index 2.0 for Predicting Cause-specific Mortality Among Persons With HIV in Europe and North America.

Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0-129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non-AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was .83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non-AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths.

Prostate Cancer Diagnosis Rates among Insured Men with and without HIV in South Africa: A Cohort Study.

Several studies have found lower prostate cancer diagnosis rates among men with human immunodeficiency virus (HIV; MWH) than men without HIV but reasons for this finding remain unclear. We used claims data from a South African private medical insurance scheme (July 2017- July 2020) to assess prostate cancer diagnosis rates among men aged ≥ 18 years with and without HIV. Using flexible parametric survival models, we estimated hazard ratios (HR) for the association between HIV and incident prostate cancer diagnoses. We accounted for potential confounding by age, population group, and sexually transmitted infections (confounder-adjusted model) and additionally for potential mediation by prostatitis diagnoses, prostate-specific antigen testing, and prostate biopsies (fully adjusted model). We included 288,194 men, of whom 20,074 (7%) were living with HIV. Prostate cancer was diagnosed in 1,614 men without HIV (median age at diagnosis: 67 years) and in 82 MWH (median age at diagnosis: 60 years). In the unadjusted analysis, prostate cancer diagnosis rates were 35% lower among MWH than men without HIV [HR, 0.65; 95% confidence interval (CI), 0.52-0.82]. However, this association was no longer evident in the confounder-adjusted model (HR, 1.03; 95% CI, 0.82-1.30) or in the fully adjusted model (HR, 1.14; 95% CI, 0.91-1.44). When accounting for potential confounders and mediators, our analysis found no evidence of lower prostate cancer diagnosis rates among MWH than men without HIV in South Africa. Our results do not support the hypothesis that HIV decreases the risk of prostate cancer.

Association of immune checkpoint inhibitor introduction and changes in survival disparities by health insurance coverage among individuals newly diagnosed with advanced cancers in the US.

1580 Background: First approved by the US Food and Drug Administration (FDA) in 2011, immune checkpoint inhibitors (ICIs) have transformed treatment options for many cancers. Unfortunately, due to their high cost, individuals without health insurance coverage may not be able to afford them. Therefore, the introduction of ICIs may lead to greater disparities in cancer survival between patients with and without health insurance. This study examined the association of health insurance with changes in survival disparities associated with the introduction of ICIs. Methods: We identified individuals newly diagnosed at age 18-64 years at stage IV with any one of the following cancers with FDA approval for ICI treatment, including melanoma (first approved 03/25/2011, n=9992); HR+ HER- female breast cancer (02/03/2015, n=13632); non-small cell lung cancer (NSCLC; 03/04/2015, n=113866); and renal cell carcinoma (RCC; 11/23/2015, n=15403) from the National Cancer Database. Individuals with private health insurance or who were uninsured at the time of the cancer diagnosis were included. For each cancer, we applied a difference-in-differences (DD) approach to examine the changes in two-year overall survival before and after the ICI FDA approval date among individuals without health insurance compared to those with private health insurance, using flexible parametric survival models and controlling for key sociodemographic factors. Results: As shown (Table), among patients diagnosed with melanoma, 2-year survival rate increased from 16.33% pre-ICI approval to 27.04% after ICI approval among patients who were uninsured and increased from 28.22% to 45.45% among patients with private health insurance, with the disparity by health insurance status widened by 4.58 (95% confidence interval [CI] = 0.02 to 9.14) percentage points (ppt) after adjusting for sociodemographic factors. For patients diagnosed with stage IV NSCLC, the disparity by health insurance widened by 1.58 (95% CI = 0.52 to 2.64) ppt. Conclusions: The introduction of ICIs increased disparities in survival by health insurance status. Policies to improve health insurance coverage options or make new treatments more affordable to uninsured patients are needed. [Table: see text]

Risk of heart failure in inflammatory bowel disease: a Swedish population-based study.

Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81,749, Crohn's disease (CD, n = 24,303), ulcerative colitis (UC, n = 45,709), and IBD-unclassified (IBD-U, n = 11,737)]. Each patient was matched with up to five general population reference individuals (n = 382,190) and IBD-free full siblings (n = 95,239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI). There were 5,582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10,000 person-years) and 20,343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15 to 1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20 to 1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09 to 1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16 to 1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03 to 1.19]). Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.

BEARING SURFACE MATERIALS AND THE RISK OF REVISION FOLLOWING PRIMARY TOTAL HIP ARTHROPLASTY: A COHORT ANALYSIS OF 1,026,481 HIP ARTHROPLASTIES FROM THE NATIONAL JOINT REGISTRY

Hip bearing surfaces materials are typically broadly reported in national registry (metal-on-polyethylene, ceramic-on-ceramic etc). We investigated the revision rates of primary total hip replacement (THR) reported in the National Joint Registry (NJR) by detailed types of bearing surfaces used.We analysed THR procedures across all orthopaedic units in England and Wales. Our analyses estimated all-cause and cause-specific revision rates. We identified primary THRs with heads and monobloc cups or modular acetabular component THRs with detailed head and shell/liner bearing material combinations. We used flexible parametric survival models to estimate adjusted hazard ratios (HR).A total of 1,026,481 primary THRs performed between 2003–2019 were included in the primary analysis (Monobloc cups: n=378,979 and Modular cups: n=647,502) with 20,869 (2%) of these primary THRs subsequently undergoing a revision episode (Monobloc: n=7,381 and Modular: n=13,488).Compared to implants with a cobalt chrome head and highly crosslinked polyethylene (HCLPE) cup, the overall risk of revision for monobloc acetabular implant was higher for patients with cobalt chrome or stainless steel head and non-HCLPE cup. The risk of revision was lower for patients with a delta ceramic head and HCLPE cup implant, at any post-operative period.Compared to patients with a cobalt chrome head and HCLPE liner primary THR, the overall risk of revision for modular acetabular implant varied non-constantly. THRs with a delta ceramic or oxidised zirconium head and HCLPE liner had a lower risk of revision throughout the entire post-operative period.The overall and indication-specific risk of prosthesis revision, at different time points following the initial implantation, is reduced for implants with a delta ceramic or oxidised zirconium head and a HCLPE liner/cup in reference to THRs with a cobalt chrome head and HCLPE liner/cup.

Long-term outcomes after hospitalization for atrial fibrillation or flutter.

Atrial fibrillation (AF) and flutter are common causes of hospitalizations but contemporary long-term outcomes following these episodes are uncertain. This study assessed outcomes up to 10 years after an acute AF or flutter hospitalization. Patients hospitalized acutely with a primary diagnosis of AF or flutter from 2008-17 from all public and most private hospitals in Australia and New Zealand were included. Kaplan-Meier methods and flexible parametric survival modelling were used to estimate survival and loss in life expectancy, respectively. Competing risk model accounting for death was used when estimating incidence of non-fatal outcomes. A total of 260 492 adults (mean age 70.5 ± 14.4 years, 49.6% female) were followed up for 1 068 009 person-years (PY), during which 69 167 died (incidence rate 6.5/100 PY) with 91.2% survival at 1 year, 72.7% at 5 years, and 55.2% at 10 years. Estimated loss in life expectancy was 2.6 years, or 16.8% of expected life expectancy. Re-hospitalizations for heart failure (2.9/100 PY), stroke (1.7/100 PY), and myocardial infarction (1.1/100 PY) were common with respective cumulative incidences of 16.8%, 11.0%, and 7.1% by 10 years. Re-hospitalization for AF or flutter occurred in 21.3% by 1 year, 35.3% by 5 years, and 41.2% by 10 years (11.6/100 PY). The cumulative incidence of patients undergoing catheter ablation of AF was 6.5% at 10 years (1.2/100 PY). Patients hospitalized for AF or flutter had high death rates with an average 2.6-year loss in life expectancy. Moreover, re-hospitalizations for AF or flutter and related outcomes such as heart failure and stroke were common with catheter ablation used infrequently for treatment, which warrant further actions.

Abstract 6095: Lung cancer risk assessment with the INTEGRAL protein panel: Preliminary results from development and validation in the Lung Cancer Cohort Consortium

Abstract Background: In the NCI-funded Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program, the Lung Cancer Cohort Consortium (LC3) recently identified 36 proteins associated with lung cancer risk in pre-diagnostic blood samples after evaluating 1,161 proteins in 731 case-control pairs (Nature Communications, 2023). Based on these data, we designed the INTEGRAL panel, which measures absolute concentrations of 21 proteins, to optimize lung cancer risk assessment for screening beyond prediction models (e.g. PLCOm2012) or categorical screening criteria (e.g. USPSTF-2021). Methods: To evaluate the performance of the INTEGRAL panel, we assayed blood from participants selected as a representative case-cohort sample from 14 LC3 cohorts, divided into development and validation sets (Annals of Epidemiology, 2023). Here, we present preliminary results from the 7 cohorts in the development set, including 807 lung cancer cases diagnosed within 3 years of blood draw and 1,144 sub-cohort representatives, who were weighted to represent all current and former smokers in their corresponding cohorts. We first fit a flexible parametric survival model in 4 cohorts (n=478 cases) including a subset of proteins and age, smoking duration, and smoking intensity. The model was subsequently evaluated in the remaining 3 cohorts (n=329 cases) and benchmarked against the PLCOm2012 risk score and USPSTF2021 screening criteria. Results: The preliminary model includes 4 proteins (CEACAM5, MMP12, SCF, LPL). Compared with the PLCOm2012 score, the model improved discrimination of future lung cancer for cases occurring over 3 years (AUC=0.81 vs. 0.76, p&amp;lt;0.0001) and over 1 year (AUC=0.86 vs. 0.78, p&amp;lt;0.0001). At the USPSTF-2021 specificity of 76%, the protein model increased sensitivity by an absolute difference of 14% over 3 years and 25% over 1 year compared to USPSTF-2021, and by 9% over 3 years and 17% over 1 year compared to the PLCOm2012 model. When screening the same number of participants as PLCOm2012, the protein model identified more future cases (223 vs 193), and the cases identified only by the protein model were predicted to gain more life-years from 3 LDCT screens compared with the PLCOm2012-identified cases (4.2 vs. 3.6 life-years). Conclusions: Preliminary results suggest that the INTEGRAL protein panel can improve risk discrimination beyond questionnaire-based risk prediction models, as well as identify future cases who have more life-years to gain from screening. Final validation is planned for completion in early 2024, by analysis of fully independent data from 7 additional LC3 cohorts (n=560 cases and 1,126 sub-cohort representatives). Citation Format: Hana Zahed, Karine Alcala, David C. Muller, Rayjean Hung, Mattias Johansson, Hilary A. Robbins, The Lung Cancer Cohort Consortium. Lung cancer risk assessment with the INTEGRAL protein panel: Preliminary results from development and validation in the Lung Cancer Cohort Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6095.

Predicting Long-Term Childhood Survival of Newborns with Congenital Heart Defects: A Population-Based, Prospective Cohort Study (EPICARD).

Backgroud: Congenital heart defects (CHDs) are the most frequent group of major congenital anomalies, accounting for almost 1% of all births. They comprise a very heterogeneous group of birth defects in terms of their severity, clinical management, epidemiology, and embryologic origins. Taking this heterogeneity into account is an important imperative to provide reliable prognostic information to patients and their caregivers, as well as to compare results between centers or to assess alternative diagnostic and treatment strategies. The Anatomic and Clinical Classification of CHD (ACC-CHD) aims to facilitate both the CHD coding process and data analysis in clinical and epidemiological studies. The objectives of the study were to (1) Describe the long-term childhood survival of newborns with CHD, and (2) Develop and validate predictive models of infant mortality based on the ACC-CHD. Methods: This study wasbased on data from a population-based, prospective cohort study: Epidemiological Study of Children with Congenital Heart Defects (EPICARD). The final study population comprised 1881 newborns with CHDs after excluding cases that were associated with chromosomal and other anomalies. Statistical analysis included non-parametric survival analysis and flexible parametric survival models. The predictive performance of models was assessed by Harrell's C index and the Royston-Sauerbrei RD2, with internal validation by bootstrap. Results: The overall 8-year survival rate for newborns with isolated CHDs was 0.96 [0.93-0.95]. There was a substantial difference between the survival rate of the categories of ACC-CHD. The highest and lowest 8-year survival rates were 0.995 [0.989-0.997] and 0.34 [0.21-0.50] for "interatrial communication abnormalities and ventricular septal defects" and "functionally univentricular heart", respectively. Model discrimination, as measured by Harrell's C, was 87% and 89% for the model with ACC-CHD alone and the full model, which included other known predictors of infant mortality, respectively. The predictive performance, as measured by RD2, was 45% and 50% for the ACC-CHD alone and the full model. These measures were essentially the same after internal validation by bootstrap. Conclusions: The ACC-CHD classification provided the basis of a highly discriminant survival model with good predictive ability for the 8-year survival of newborns with CHDs. Prediction of individual outcomes remains an important clinical and statistical challenge.

Socioeconomic Status and Overall Survival Among Patients With Hematological Malignant Neoplasms

In recent years, there has been a focus on reducing the socioeconomic gap in survival for hematological malignant neoplasms. Understanding recent developments is important to develop further intervention to improve care. To investigate the temporal trend in associations of socioeconomic status (SES) with survival among 3 aggressive hematological malignant neoplasms: multiple myeloma (MM), acute myeloid leukemia (AML), and diffuse large B-cell lymphoma (DLBCL). This nationwide, population-based cohort study used retrospectively collected data from 3 clinical registries of patients diagnosed in Denmark between January 1, 2005, and December 31, 2020, with follow-up until December 31, 2021. Analyses were stratified by diagnosis year (2005-2009, 2010-2014, and 2015-2020). Participants were patients aged 25 to 65 years with hematological malignant neoplasms. Patients with missing data on education were excluded. Data were analyzed from October 14, 2022, to January 2, 2024. Education was used as a proxy for SES and defined low- and high-SES groups based on the completion of tertiary education. The main outcome was overall survival (OS), analyzed using Kaplan-Meier (log rank) method and Cox proportional hazards regression adjusted for age, sex, performance status, comorbidities, and disease-specific prognostic indices. Two-year OS through time and survival difference were estimated using flexible parametric survival models. A total of 5677 patients (median [IQR] age, 58 [51-62] years; 3177 [57.0%] male) were assessed, including 1826 patients with MM, 1236 patients with AML, and 2509 patients with DLBCL. The 2-year OS increased over time for patients with MM (78.8% [95% CI, 75.4%-82.3%] to 91.4% [95% CI, 89.3%-93.5%]), AML (42.2% [95% CI, 37.8%-47.1%] to 52.7% [95% CI, 48.0%-57.9%]), and DLBCL (80.1% [95% CI, 77.4%-82.8%] to 88.1% [95% CI, 86.0%-90.3%]). For MM and DLBCL, no association of SES with survival was observed after adjustment (MM: hazard ratio [HR], 0.99 [95% CI, 0.85-1.15]; DLBCL: HR, 1.08 [95% CI, 0.91-1.29]). For AML, a negative association was observed between low SES and survival (HR, 1.49 [95% CI, 1.25-1.76]), but the association was attenuated in recent years. The difference in hazard for patients with low SES and AML was observed in the first 2 years after diagnosis. These findings suggest that survival has improved among patients with these hematological malignant neoplasms. While patients with MM and DLBCL had increased survival in all groups, disparities were observed in AML outcomes, primarily in the first years after diagnosis. These results suggest that differences originate in factors specific to AML.

Survival trends for patients diagnosed with cutaneous malignant melanoma in the Nordic countries 1990-2016: The NORDCAN survival studies

BackgroundThe survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men. MethodsPatients diagnosed with CMM in the Nordic countries in 1990–2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific. ResultsThe 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men. ConclusionAlthough survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age.

Post-injury long-term sickness absence and risk of disability pension: the role of socioeconomic status

Previous research has identified low socioeconomic status (SES) as a risk factor for long-term sickness absence (LTSA) and disability pension (DP) following trauma. However, most studies lack information on medical diagnoses, limiting our understanding of the underlying factors. To address this gap, we retrieved information about diagnostic causes for receipt of welfare benefits to explore the role of SES in the transition from post-injury LTSA to permanent DP among the working population in Norway. We conducted a population-based cohort study of all Norwegian residents aged 25-59 years registered with a spell of LTSA due to injury commencing in the period 2000-2003. This cohort was followed through 2014 by linking information on receipt of welfare benefits with sociodemographic data from administrative registers. SES was defined as a composite measure of educational attainment and income level. We used flexible parametric survival models to estimate hazard ratios (HR) with 95 % confidence intervals (CI) for all-cause and diagnosis-specific DP according to SES, adjusting for sex, age, marital status, immigrant status and healthcare region of residence. Of 53,937 adults with post-injury LTSA, 9,665 (18 %) transferred to DP during follow-up. The crude risk of DP was highest for LTSA spells due to poisoning and head injuries. Overall, individuals in the lowest SES category had twice the risk of DP compared to those in the highest SES category (HR = 2.25, 95 % CI 2.13-2.38). The difference by SES was greatest for LTSA due to poisoning and smallest for LTSA due to head injuries. A majority (75 %) of DP recipients had a non-injury diagnosis as the primary cause of DP. The socioeconomic gradient was more pronounced for non-injury causes of DP (HR = 2.47, 95 % CI 2.31-2.63) than for injury causes (HR = 1.73, 95 % CI 1.56-1.92) and was especially steep for DP due to musculoskeletal diseases and mental and behavioural disorders. The relationship between SES and DP varied by both the type of injury that caused LTSA and the diagnosis used to grant DP, highlighting the importance of taking diagnostic information into account when investigating long-term consequences of injuries.

Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden.

Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.

Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC. Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used. A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN). With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.

P1146 Familial Coaggregation of Inflammatory Bowel Disease with Cardiovascular Disease: a Nationwide Multigenerational Cohort Study

Abstract Background Genetics contribute to the development of both inflammatory bowel disease (IBD) and cardiovascular disease (CVD). Although an increased risk of CVD has been documented in IBD patients, little is known about the risk of CVD in family members of patients with IBD. Methods In this Swedish nationwide multigenerational cohort, we identified patients with biopsy-confirmed IBD (≥18 years) who had at least one family member living in Sweden at their date of diagnosis from 1969 through 2017. Each patient was matched with up to five IBD-free reference individuals from the general population. We then identified 205,642 first-degree relatives (FDRs: father, mother, full-siblings, offspring) and 44,790 spouses of IBD patients as well as 1,015,010 FDRs and 222,969 spouses of their reference individuals. These family members were followed from the later date of turning 18 years or their linked IBD patients/reference individuals being diagnosed/matched (i.e., index date), until the interested CVD outcome, heart transplant, emigration, death, or 31/12/2020, whichever came first. The primary outcome was any incident CVD and CVD mortality. Secondary outcomes included incident ischemic heart disease, heart failure, cerebrovascular disease, deep vein thromboembolism, pulmonary embolism, and atrial fibrillation/flutter. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) with 95% confidence interval (CI). Results FDRs of IBD patients were at higher risks of incident CVD (aHR=1.04, 95%CI: 1.03 to 1.05) and CVD mortality (aHR=1.03 [1.00 to 1.06]) than FDRs of reference individuals (Figure 1). The increased risks were significant for almost all secondary outcomes, with point estimates hovering around a two to eight percent increased risk. Similar patterns were observed by IBD subtypes, sex, age and calendar period at index date, and family relationship of FDRs. In contrast, spouses demonstrated no increased risks of incident CVD or CVD mortality. Conclusion Relative risks of incident CVD and CVD mortality were only slightly increased in FDRs of patients with IBD, but not at all in spouses, suggesting no need for extra vigilance for CVD among family members of IBD patients.