Flexible Parametric Survival Models Research Articles

Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study

Co-occurrence of inflammatory bowel disease (IBD) and type 1 diabetes (T1D) has been linked to poor clinical outcomes, but evidence on their bidirectional associations remain scarce. This study aims to investigate their bidirectional associations. A nationwide matched cohort and case-control study with IBD patients identified between 1987 and 2017. The cohort study included 20,314 IBD patients (≤28 years; Crohn's disease [CD, n=7277], ulcerative colitis [UC, n=10,112], and IBD-unclassified [IBD-U, n=2925]) and 99,200 individually matched reference individuals, with a follow-up until December 2021. The case-control study enrolled 87,001 IBD patients (no age restriction) and 431,054 matched controls. We estimated adjusted hazard ratio (aHR) of incident T1D in the cohort study with flexible parametric survival model and adjusted odds ratio (aOR) of having a prior T1D in the case-control study with conditional logistic regression model, with 95% confidence intervals (CI). During a median follow-up of 14 years, 116 IBD patients and 353 reference individuals developed T1D. Patients with IBD had a higher hazard of developing T1D (aHR=1.58 [95% CI=1.27-1.95]). The hazard was increased in UC (aHR=2.02 [1.51-2.70]) but not in CD or IBD-U. In the case-control study, a total of 1018 (1.2%) IBD patients and 3496 (0.8%) controls had been previously diagnosed with T1D. IBD patients had higher odds of having prior T1D (aOR=1.36 [1.26-1.46]). Such positive association was observed in all IBD subtypes. The sibling comparison analyses showed similar associations between IBD and T1D (aHR=1.44 [0.97-2.15] and aOR=1.32 [1.18-1.49]). Patients with IBD had a moderately increased hazard of developing T1D and higher odds of having prior T1D. Their bidirectional associations may be partially independent of shared familial factors. European Crohn's and Colitis Organisation, Stiftelsen Professor Nanna Svartz Fond, SSMF (project#: PG-23-0315-H-02), Ruth and Richard Julin Foundation; and FORTE (project#: 2016-00424).

Association of innate versus specific immunity with heart failure incidence: a prospective study.

Immune disorders are key heart failure (HF) triggers, but little is known about whether the status of immunity affects the incidence of HF. To explore this, we used blood cell counts and derived ratios to investigate the association between immunity status markers and HF incidence. The number and proportion of peripheral blood leucocytes in a physiological state are related to the body's immune status. Neutrophils, monocytes, SII (systemic immune-inflammatory index), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) serve as innate immunity status markers, while lymphocytes and LMR (lymphocyte-to-monocyte ratio) serve as specific immunity status markers. 330 362 UK Biobank (UKB) participants were finally examined. Cox proportional hazard models were used to explore the relationship between immunity status markers and HF incidence. Flexible parametric survival models were used to capture time-varying relationships between blood cell ratios and HRs for HF. Subgroup analyses were conducted by age, sex, and body mass index. Finally, sensitivity analyses were performed to validate the results. During a median follow-up of 14.1 years, 9611 (2.9%) participants developed HF. Neutrophils, monocytes, SII, and NLR were positively associated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 1.20 (1.17 to 1.22), 1.09 (1.07 to 1.12), 1.12 (1.10 to 1.14), and 1.16 (1.14 to 1.18), respectively. Platelets, lymphocytes, and LMR were inversely correlated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 0.97 (0.95 to 1.00), 0.97 (0.95 to 0.99), and 0.90 (0.88 to 0.92), respectively. The innate immunity status markers were positively associated with HF incidence, while specific immunity status markers exhibited an inverse association, offering novel insights for HF prediction and intervention.

Causes of death among patients diagnosed with chronic lymphocytic leukemia: A population-based study in the Netherlands, 1996-2020.

Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population-based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause-specific flexible parametric survival models, we estimated cause-specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5-year death probability from 16.8% in 1996-2002 to 7.6% in 2010-2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%-0.77%), 0.45 (0.38%-0.53%), and 0.77 (0.66%-0.90%). In summary, our comprehensive, population-based analysis underscores a noticeable reduction in CLL-attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL-centric clinical strategies and research.

Management and outcomes of acute myocardial infarction in patients with Alzheimer's disease: a study of 2.7 million individuals with myocardial infarction, 2010 - 2020

Abstract Background As a consequence of population ageing, the prevalence of Alzheimer’s Disease (AD) is rising. Evidence-based clinical decision-making for those with AD that present with acute myocardial infarction (MI) is limited by difficulty in identifying which patients will benefit from guideline-directed invasive management versus a more conservative approach. Purpose This study aimed to assess the prevalence of AD in patients presenting with acute MI and characterise its association with patient factors, treatment utilisation and clinical outcomes. Methods A retrospective cohort study was conducted using the United States National Readmission Database (NRD), 2010–2020. International Classification of Disease (ICD; version 9 and 10, Clinical Modification) codes were used to identify patients with a principal diagnosis of MI, pre-existing AD and other comorbidities, in addition to invasive procedures (invasive coronary angiography ± percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery). Logistic and flexible parametric survival models (adjusted for age, sex, MI subtype, smoking status, comorbidities, and MI treatments) were used to evaluate the association between AD and in-hospital and 1-year clinical outcomes, respectively. Results Overall, 2,750,798 individuals were admitted with MI during the study period, of which 35,367 had Alzheimer’s disease; 1.3%; Figure 1). Patients with AD were older (median age 85 vs. 67), more likely to be female (57.6 vs. 37.9%), present with non-ST-elevation MI (77.7 vs. 69.5%), and had a greater burden of individual comorbidities (including chronic kidney disease and depression) and multimorbidity (≥2 long-term conditions; 77.4 vs. 71.0%). Patients with AD were less likely to undergo invasive management (coronary angiography ± PCI/CABG; 27.7 vs 77.6%; p < 0.001; adjusted odds ratio [aOR] 0.24, 95% confidence intervals [CI] 0.23–0.25). Patients with AD had greater mortality both in-hospital (11.9 vs. 5.2%; aOR 1.30 (95% CI: 1.26–1.35, p < 0.001) and 1-year (15.9 vs. 7.3%; adjusted hazard ratio [aHR] 1.21; 95% CI 1.18–1.25). AD was associated with a greater risk of major adverse cardiovascular events (MACE; myocardial infarction, stroke or all-cause mortality; 27.8 vs. 17.7%; aHR 1.10, 95% CI 1.08–1.12) at 1-year post-MI (figure 2). However, patients with AD that were selected to undergo invasive management experienced reduced MACE (aHR 0.74, 95% CI 0.70–0.77) and all-cause mortality (aHR 0.53, 95% CI 0.49–0.57) in comparison to those managed conservatively. Conclusions Patients with Alzheimer’s Disease presenting with acute MI face a poor prognosis marked by a high rate of MACE and all-cause mortality. Future research should seek to identify those who benefit most from invasive management. At present, individualised, shared and multidisciplinary decision-making is key to guide the management of patients with AD that present with acute MI.

Association of Medicaid Expansion With Timely Receipt of Treatment and Survival Among Patients With HR-Negative, HER2-Positive Breast Cancer.

Hormone receptor (HR)-negative, HER2-positive (also called HER2-enriched) breast cancer has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its association with receipt of care for HR-negative, HER2-positive breast cancer is unknown. We examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment initiation, and survival among nonelderly women newly diagnosed with HR-negative, HER2-positive breast cancer. Women aged 18 to 62 years newly diagnosed with HR-negative, HER2-positive breast cancer between 2010 and 2018 were identified from the National Cancer Database. Outcomes included receipt of stage-based guideline-concordant treatment, timely initiation of treatment (<30 days, <60 days, <90 days from diagnosis), and stage-specific 2-year overall survival. A difference-in-differences (DID) analytic approach compared outcome changes following Medicaid expansion in expansion versus nonexpansion states. Multivariable linear probability models were used to estimate treatment outcomes, and flexible parametric survival models were used to evaluate survival, adjusting for sociodemographic and clinical confounders. A total of 31,401 patients were included. Medicaid expansion was associated with an increase of 0.58 percentage points (ppt; 95% CI, 0.01-1.16) in receipt of guideline-concordant treatment overall, a 2.43-ppt (95% CI, 0.68-4.18) increase in initiating guideline-concordant treatment <60 days after diagnosis, and a 1.17-ppt (95% CI, 0.02-2.32) increase in 2-year survival rate. The increase in 2-year survival associated with Medicaid expansion was most prominent for patients with stage III disease (DID, 3.81; 95% CI, 0.82-6.80). Medicaid expansion was associated with improved care and survival for patients with HR-negative, HER2-positive breast cancer, an aggressive cancer type for which prognosis largely depends on access to effective treatment.

Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Association between surgeon training grade and the risk of revision following unicompartmental knee replacement: An analysis of National Joint Registry data.

Unicompartmental knee replacements (UKRs) are performed by surgeons at various stages in training with varying levels of supervision, but we do not know if this is a safe practice with comparable outcomes to consultant-performed UKR. The aim of this study was to use registry data for England and Wales to investigate the association between surgeon grade (consultant, or trainee), the senior supervision of trainees (supervised by a scrubbed consultant, or not), and the risk of revision surgery following UKR. We conducted an observational study using prospectively collected data from the National Joint Registry for England and Wales (NJR). We included adult patients who underwent primary UKR for osteoarthritis (n = 106,206), recorded in the NJR between 2003 and 2019. Exposures were the grade of the operating surgeon (consultant, or trainee) and whether or not trainees were directly supervised by a consultant during the procedure (referred to as "supervised by a scrubbed consultant"). The primary outcome was all-cause revision surgery. The secondary outcome was the number of procedures revised for the following specific indications: aseptic loosening/lysis, infection, progression of osteoarthritis, unexplained pain, and instability. Flexible parametric survival models were adjusted for patient, operation, and healthcare setting factors. We included 106,206 UKRs in 91,626 patients, of which 4,382 (4.1%) procedures were performed by a trainee. The unadjusted cumulative probability of failure at 15 years was 17.13% (95% CI [16.44, 17.85]) for consultants, 16.42% (95% CI [14.09, 19.08]) for trainees overall, 15.98% (95% CI [13.36, 19.07]) for trainees supervised by a scrubbed consultant, and 17.32% (95% CI [13.24, 22.50]) for trainees not supervised by a scrubbed consultant. There was no association between surgeon grade and all-cause revision in either crude or adjusted models (adjusted HR = 1.01, 95% CI [0.90, 1.13]; p = 0.88). Trainees achieved comparable all-cause survival to consultants, regardless of the level of scrubbed consultant supervision (supervised: adjusted HR = 0.99, 95% CI [0.87, 1.14]; p = 0.94; unsupervised: adjusted HR = 1.03, 95% CI [0.87, 1.22]; p = 0.74). Limitations of this study relate to its observational design and include: the potential for nonrandom allocation of cases by consultants to trainees; residual confounding; and the use of the binary variable "surgeon grade," which does not capture variations in the level of experience between trainees. This nationwide study of UKRs with over 16 years' follow up demonstrates that trainees within the current training system in England and Wales achieve comparable all-cause implant survival to consultants. These findings support the current methods by which surgeons in England and Wales are trained to perform UKR.

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.

Association of serum calcium, vitamin D, and C-reactive protein with all-cause and cause-specific mortality in an osteoarthritis population in the UK: a prospective cohort study

BackgroundOsteoarthritis is a prevalent musculoskeletal condition, but the role of specific serum biomarkers, such as calcium, vitamin D, and C-reactive protein (CRP), in predicting mortality among individuals with osteoarthritis remains unclear.MethodsThis observational study analyzed longitudinal data from over 500,000 participants in the UK Biobank, identifying those with osteoarthritis using ICD-9/10 codes or self-reported history. We performed multivariable cox-regression and flexible parametric survival model (FPSM) for survival analysis, with adjustments made through the inverse probability of treatment weight (IPTW) for baseline covariates identified by directed acyclic graphs (DAGs).ResultsOf the 49,082 osteoarthritis population, the average age was 60.69 years, with 58.7% being female. During the follow-up period exceeding 15 years, a total of 5,522 people with osteoarthritis died. High serum calcium levels, compared to normal serum calcium levels, were significantly associated with all-cause mortality (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11, 1.59), cardiovascular diseases (CVD)-related deaths (HR 1.55, 95% CI 1.05, 2.29), and other deaths (HR 1.59, 95% CI 1.20, 2.11). Low serum calcium levels, compared to normal serum calcium levels, was linked with CVD-related deaths (HR 2.06, 95% CI 1.02, 4.14). Vitamin D insufficiency, compared to sufficient vitamin D levels, was correlated with all-cause mortality (HR 1.22, 95% CI 1.13, 1.33), CVD-related deaths (HR 1.43, 95% CI 1.20, 1.72), and other deaths (HR 1.26, 95% CI 1.09, 1.45) but not with cancer-related deaths. High serum CRP levels, compared to normal CRP levels, were associated with all outcomes (all-cause mortality: HR 1.22, 95% CI 1.12, 1.33; CVD-related death: HR 1.24, 95%CI 1.03, 1.49; cancer-related death: HR 1.23, 95% CI 1.09, 1.40; other deaths: HR 1.19, 95%CI 1.03, 1.38).ConclusionsBoth high and low serum calcium levels, elevated CRP, and vitamin D insufficiency are potential predictors of increased mortality risk in the osteoarthritis population. These findings emphasize the importance of monitoring and possibly addressing these serum biomarkers in osteoarthritis populations to improve long-term outcomes. Further studies are needed to understand the underlying mechanisms and to propose therapeutic interventions.

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

We investigated the revision rates of primary total hip replacement (THR) reported in the National Joint Registry (NJR) by 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 head and shell/liner 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 are included in the primary analysis (Monobloc: n=378,979 and Modular: 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 all-cause 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 all-cause 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 all-cause and indication-specific risk of prosthesis revision, at different time points following the initial implantation, is lower for implants with a delta ceramic or oxidised zirconium head and a HCLPE liner/cup than commonly used alternatives such as cobalt chrome heads and HCLPE liner/cup.

Association Between Adverse Early Life Factors and Telomere Length in Middle and Late Life.

Telomere length (TL) has been acknowledged as biomarker of biological aging. Numerous investigations have examined associations between individual early life factors and leukocyte TL; however, the findings were far from consistent. We evaluated the relationship between individual and combined early life factors and leukocytes TL in middle and late life using data from the UK Biobank. The early life factors (eg, maternal smoking, breastfeeding, birth weight, and comparative body size and height to peers at age 10) were measured. The regression coefficients (β) and 95% confidence interval (CI) were applied to assess the link of the early life factors and TL in adulthood. Flexible parametric survival models incorporated age to calculate the relationship between early life factors and life expectancy. Exposure to maternal smoking, lack of breastfeeding, low birth weight, and shorter height compared to peers at age 10 were identified to be associated with shorter TL in middle and older age according to the large population-based study with 197 504 participants. Individuals who experienced more than 3 adverse early life factors had the shortest TL in middle and late life (β = -0.053; 95% CI = -0.069 to -0.038; p < .0001), as well as an average of 0.54 years of life loss at the age of 45 and 0.49 years of life loss at the age of 60, compared to those who were not exposed to any early life risk factors. Early life factors including maternal smoking, non-breastfed, low birth weight, and shorter height compared to peers at age 10 were associated with shorter TL in later life. In addition, an increased number of the aforementioned factors was associated with a greater likelihood of shorter TL in adulthood, as well as a reduced life expectancy.

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.

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 aged more than 55 years who had primary osteoarthritis were studied. Metal-on-highly cross-linked polyethylene (MoXLP), ceramic-on-highly cross-linked 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 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% CI 95.6 to 96.1) in CoXLP, 96.7% (95% CI 96.4 to 97.0) in CoC, and 93.9% (95% CI 93.5 to 94.4) in MoM. The 10-years 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 (HR 1.0, CI 0.9 to 1.0), and higher in MoM (HR 1.3, CI 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 highly cross-linked polyethylene bearings.

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.

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.

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.