Flexible Parametric Survival Models Research Articles

Education level is associated with the occurrence and timing of hysterectomy: A cohort study of Canadian women.

Hysterectomy is a common surgery with discernible practice variations that could be influenced by socioeconomic factors. We examined the association between level of educational attainment and the occurrence and timing of hysterectomy in Canadian women. We conducted a prospective cohort study of 30 496 females in the Alberta's Tomorrow Project (2000-2015) followed approximately every 4 years using self-report questionnaires. Educational attainment was defined as high school diploma or less, college degree, university degree (reference group), and postgraduate degree. We used logistic regression analyzing hysterectomy occurrence at any time and before menopause, separately, and flexible parametric survival models analyzing hysterectomy timing with age as the time scale. Multivariable models controlled for race/ethnicity, rural/urban residence, parity, oral contraceptive use, and smoking. Overall, 39.1% of females reported a high school diploma or less, 28.9% reported a college degree, 23.5% reported a university degree, and 8.5% reported a postgraduate degree. A graded association was observed between lower education and higher odds of hysterectomy (high school or less: adjusted odds ratio [AOR] 1.68, 95% CI 1.55-1.82; college degree: AOR 1.58, 95% CI 1.45-1.72); results were similar for premenopausal hysterectomy. A graded association between lower education and earlier timing of hysterectomy was also observed up to approximately age 60 (e.g., at age 40: high school or less adjusted hazard ratio [AHR] 1.61, 95% CI 1.49-1.75; college degree AHR 1.53, 95% CI 1.40-1.67). Women with lower levels of education were more likely to experience hysterectomy, including hysterectomy before menopause and at younger ages.

Association of baseline and changes in health-related quality of life with mortality following myocardial infarction: multicentre longitudinal linked cohort study.

Health-related quality of life (HRQoL) for patients following myocardial infarction (MI) is frequently impaired. We investigated the association of baseline and changes in HRQoL with mortality following MI. Nationwide longitudinal study of 9474 patients admitted to 77 hospitals in England as part of the Evaluation of the Methods and Management of Acute Coronary Events study. Self-reported HRQoL was collected using EuroQol EQ-5D-3L during hospitalization and at 1, 6, and 12 months following discharge. The data was analysed using flexible parametric and multilevel survival models. Of 9474 individuals with MI, 2360 (25%) were women and 2135 (22.5%) died during the 9-year follow-up period. HRQoL improved over 12 months (baseline mean, mean increase: EQ-5D 0.76, 0.003 per month; EQ-VAS 69.0, 0.5 per month). At baseline, better HRQoL was inversely associated with mortality [Hazard ratio (HR) 0.55, 95% CI 0.47-0.63], and problems with self-care (HR 1.73, 1.56-1.92), mobility (1.65, 1.50-1.81), usual activities (1.34, 1.23-1.47), and pain/discomfort (1.34, 1.22-1.46) were associated with increased mortality. Deterioration in mobility, pain/discomfort, usual activities, and self-care over 12 months were associated with increased mortality (HR 1.43, 95% CI 1.31-1.58; 1.21, 1.11-1.32; 1.20, 1.10-1.32; 1.44, 1.30-1.59, respectively). After MI, poor HRQoL at baseline, its dimensions, and deterioration over time are associated with an increased risk of mortality. Measuring HRQoL in routine clinical practice after MI could identify at-risk groups for interventions to improve prognosis.

Avoidable Hospitalizations in Frail Older Adults: The Role of Sociodemographic, Clinical, and Care-Related Factors

ObjectivesThis study aims to investigate the relationship between frailty and avoidable hospitalization risk, and the moderating role of sociodemographic, clinical, and care-related factors. DesignLongitudinal population-based cohort study. Setting and ParticipantsA total of 3168 community-dwelling individuals, aged ≥60 years, from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). MethodsWe operationalized physical frailty using baseline SNAC-K data (2001-2004). In line with the Swedish Board of Health and Welfare and Association of Local Authorities and Regions, avoidable hospitalizations were considered those that could have been prevented through proper and timely outpatient care and identified through the Swedish National Patient Register. Participants were followed from baseline until first avoidable hospitalization, death, drop out, institutionalization, or maximum 12 (median 7.6) years. The association between frailty and avoidable hospitalization was explored through flexible parametric survival models, with stratified analyses to investigate age, gender, education, civil status, multimorbidity, cognitive status, and informal and formal care as potential modifiers. ResultsThe adjusted 12-year cumulative incidence of avoidable hospitalization was significantly higher for frail persons (cumulative incidence 33.2%, 95% CI 28.9%-38.1%) than for prefrail (cumulative incidence 26.6%, 95% CI 24.5%-29.0%) and nonfrail (cumulative incidence 25.2%, 95% CI 22.5%-28.3%) individuals. In addition, prefrailty [hazard ratio (HR) 1.21, 95% CI 1.00-1.45] and frailty (HR 1.91, 95% CI 1.47-2.50) were associated with increased avoidable hospitalization hazards. Furthermore, the association between frailty and avoidable hospitalization was stronger in older adults aged <78 years (HR 3.12, 95% CI 1.99-4.91) and those with relatively fewer chronic diseases (HR 3.88, 95% CI 1.95-7.72), whereas provision of formal social care (HR 1.15, 95% CI 0.77-1.72) seemed to act as a buffer. Conclusions and ImplicationsOur results indicate that older community-dwelling adults with prefrailty and frailty are at increased risk of experiencing avoidable hospitalizations, highlighting a need for better care of these individuals at the outpatient level. Formal social care services and close monitoring of particularly vulnerable subgroups of frail persons may mitigate this risk.

Choice of Bearings Influences the Implant Survival of Total Hip Arthroplasty in Patients Who Have Osteoarthritis Aged 55 Years or More: Results of 158,044 Patients from the Nordic Arthroplasty Register Association from 2005 to 2017

BackgroundThe aim of our study was to compare implant survival rates of different total hip arthroplasty (THA) bearings in the Nordic Arthroplasty Register Association. MethodsAll conventional primary THAs performed between 2005 and 2017 in patients over 55 years of age who had primary osteoarthritis were studied. Metal-on-highly crosslinked polyethylene (MoXLP), ceramic-on-highly crosslinked polyethylene (CoXLP), ceramic-on-ceramic (CoC), and metal-on-metal (MoM) bearings were included. The outcome was a revision. Kaplan-Meier (KM) estimates were calculated at 5 and 10 years. The risk for revision was analyzed using a flexible parametric survival model (FPSM) adjusted for nation, age, sex, femoral head size, and femoral fixation. ResultsA total of 158,044 THAs were included. The 5-year KM estimates were 95.9% (95% confidence interval [CI] 95.8 to 96.1) in MoXLP, 95.8% (95.6 to 96.1) in CoXLP, 96.7% (96.4 to 97.0) in CoC, and 93.9% (93.5 to 94.4) in MoM. The 10-year KM estimates were 94.2% (94.0 to 94.5) in MoXLP, 94.3% (93.9 to 94.8) in CoXLP, 95.4% (95.0 to 95.9) in CoC, and 85.5% (84.9 to 86.2) in MoM. Compared with MoXLP, the adjusted risk for revision was lower in CoC (hazard ratio [HR] 0.6, CI 0.5 to 0.6), similar in CoXLP (1.0, 0.9 to 1.0), and higher in MoM (1.3, 1.2 to 1.4). ConclusionsWe found that MoXLP, CoXLP, and CoC bearings evinced comparably high implant survival rates up to 10 years, and they can all be regarded as safe options in this patient group. The MoM bearings were associated with clearly lower survivorship. The CoC bearings had the highest implant survival and a lower adjusted risk for revision compared with XLP bearings.

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.

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.

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.

Skeletonized Versus Pedicled Harvesting of the Internal Thoracic Artery and Long-Term Clinical Outcomes in Coronary Artery Bypass Surgery.

The internal thoracic artery (ITA) is the most important conduit for coronary artery bypass grafting. Recent evidence suggests that skeletonized ITA harvesting yields long-term outcomes inferior to those of pedicled harvesting. The aim was to investigate the impact of the ITA harvesting method on 10-year mortality and major adverse cardiovascular events. In this observational cohort study, we identified all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent isolated coronary artery bypass grafting using at least 1 ITA at Karolinska University Hospital from 2012 to 2021. The main outcome was all-cause mortality, and the secondary outcomes were a combination of myocardial infarction, repeat revascularization, heart failure, and stroke. Outcomes were ascertained using national health data registers and compared between the skeletonized and pedicled groups using weighted flexible parametric survival models. Among 3267 patients, 1657 (51%) underwent pedicled ITA harvesting and 1610 (49%) underwent skeletonized ITA harvesting. The patients' mean age was 66 years, and 15% were women. The weighted all-cause mortality incidence rate in the pedicled versus skeletonized ITA group was 2.6% (95CI, 2.2%-3.0%) versus 2.6% (95% CI, 2.2%-3.1%), respectively (hazard ratio (HR), 1.01 [95% CI, 0.81-1.27]). The weighted major adverse cardiovascular events incidence rate was 7.8% (95% CI, 7.1%-8.6%) versus 7.5% (95% CI, 6.7%-8.4%), respectively (HR, 0.94 [95% CI, 0.82-1.08]). We found no significant differences in all-cause mortality or major adverse cardiovascular events rates between the 2 ITA harvesting methods.

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]

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study

There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

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 5582 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 1.15-1.23). 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 [1.20-1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09-1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16-1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03-1.19]). 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.