Flexible Parametric Survival Models Research Articles

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 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 (07/2017-07/2020) 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 (PSA) 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 men with HIV than men without HIV in South Africa. Our results do not support the hypothesis that HIV decreases the risk of prostate cancer.

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<0.0001) and over 1 year (AUC=0.86 vs. 0.78, p<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.

P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort study

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD. Methods The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress. Results In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients. Conclusion The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.

Abstract A009: Association between unstable diabetes mellitus and risk of pancreatic cancer

Abstract Worsening of hyperglycemia in people with pre-existing diabetes mellitus may be an indicator of undiagnosed pancreatic cancer. However, there is limited evidence from longitudinal studies regarding the association between deterioration of diabetes and pancreatic cancer in people with previously stable diabetes. The size of the association between deterioration of diabetes and pancreatic cancer, and how the association changes over time, needs further investigation. A population-based matched cohort study was conducted within Australian women with stable diabetes mellitus. Unstable diabetes, the exposure of interest, was defined as change in the type of antidiabetic medication or addition of another antidiabetic medication after at least 24 months of stable antidiabetic medication use. The date of exposure was defined as the index date. Each woman with unstable diabetes was matched to 4 women with stable diabetes by birth year (±1 year) at the index date. Flexible parametric survival models were used to estimate hazard ratios (HR) (overall and at different times) and 95% confidence intervals (CI), and absolute risk in both groups at different time points. We identified 134,954 women with unstable diabetes; these were matched to women who had not developed unstable diabetes at the index date. The mean age of the cohort was 68 years. Over a median follow-up period of 2.8 years, 1,315 pancreatic cancer cases were diagnosed. Overall, women who experienced deterioration in glycemic control had a 2.5-fold increased risk of developing pancreatic cancer (HR 2.55; 95% CI 2.29 – 2.85). The risk was very high during the initial few months [HRs at 3 months (5.76; 95% CI 4.72 – 7.04), 6 months (4.56; 95% CI 3.81 – 5.46), and 12 months (3.33; 95% CI 2.86 – 3.89)]. The risk then progressively declined with time. Worsening of glycemic control in those with previously stable diabetes may be an early clinical manifestation of pancreatic cancer. Further research is warranted to differentiate this pancreatic cancer-associated deterioration of glycemic control from other causes. The longer-term (3-7 years) weaker association between pancreatic cancer and deterioration of glycemic control suggests that poorly controlled hyperglycemia is a predisposing factor for pancreatic cancer. Citation Format: Sitwat Ali, Michael Coory, Peter Donovan, Renhua Na, Nirmala Pandeya, Sallie-Anne Pearson, Katrina Spilsbury, Louise Stewart, Bridie Thompson, Karen Tuesley, Mary Waterhouse, Penelope Webb, Susan Jordan, Rachel Neale. Association between unstable diabetes mellitus and risk of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A009.

Loss in life expectancy in patients with stage II-III cutaneous melanoma in Sweden: A population-based cohort study

BackgroundSurvival in cutaneous melanoma (CM) is heterogeneous. Loss in life expectancy (LLE) measures impact of CM on remaining lifespan compared to general population. ObjectivesInvestigating LLE in operated stage II-III CM patients. MethodsData from 8,061 patients (aged 40-80 years) with stage II–III CM in Sweden, diagnosed between 2005-2018 were analyzed (Swedish Melanoma Registry). A flexible parametric survival model estimated life expectancy and LLE. ResultsBased on 2018 diagnoses, stage II and III CM patients lost 2209 and 1902 life years, respectively. LLE was higher in stage III: 5.2 vs 10.9 years (stage II vs III 60-year-old females). Younger patients had higher LLE: 10.7 vs 3.9 years (stage II CM in 40 vs 70-year-old males). In stage II, females had lower LLE than males; 50-year-old females and males stage II CM had LLE equal to 7.3 and 8.3 years, respectively. LLE increased with higher substages, stage IIB resembling IIIB and IIC resembling IIIC-D. LimitationsExtrapolation was used to estimate LLE. Varying stage group sizes require caution. ConclusionsOur results are both clinically relevant and easy-to-interpret measures of the impact of CM on survival, but the results also summarize the prognosis over the lifetime of a CM patient.

Associations of Orthostatic Hypotension and Frailty With Dementia and Mortality in Older Adults: A Population-Based Cohort Study.

This study aimed to assess the associations of orthostatic hypotension (OH), in the presence or absence of frailty, with dementia and mortality in older adults. We conducted a 15-year population-based cohort study including 2703 baseline dementia-free individuals from the Swedish National Study on Aging and Care in Kungsholmen. At baseline, OH was defined as a decline in systolic/diastolic blood pressure ≥20/10mm Hg 1 minute after standing up from a supine position. Frailty status was defined following Fried's frailty phenotype. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders-fourth edition criteria. Multistate flexible parametric survival models were used to estimate associations of OH and frailty with dementia and mortality. Robust people with OH (adjusted hazard ratio [HR] = 2.28; 95% confidence interval [CI] = 1.47-3.54) and frail people without OH (HR = 1.98; 95% CI = 1.40-2.82) or with OH (HR = 2.73; 95% CI = 1.82-4.10) had a higher dementia risk than OH-free and robust people. Moreover, frail people, independently of the presence of OH, had higher mortality rate than OH-free and robust people. In individuals who developed dementia during the follow-up period, neither OH nor frailty was significantly associated with mortality. Older adults with OH, whether robust or frail, may have a higher dementia risk than those without OH. Older adults with OH, when having frailty, may have a higher mortality rate than those without OH. The concurrent assessments of OH and frailty may provide prognostic values in terms of dementia and mortality risk in older adults.

High Adherence to a Mediterranean Alcohol-Drinking Pattern and Mediterranean Diet Can Mitigate the Harmful Effect of Alcohol on Mortality Risk.

Alcohol is a psychoactive substance with deleterious effects on human health and mortality. This study aims to investigate the joint associations between the Mediterranean Diet (MedDiet), alcohol- consumption patterns and mortality from the following: all causes, cardiovascular, neoplastic, the digestive system, and other causes. A sample of 3411 alcohol consumers aged ≥18 years was selected from two prospective cohort studies: the MICOL and NUTRIHEP Study. Cohorts were enrolled in 2005-2006, and followed up until December 2022, capturing data on alcohol consumption, diet, and mortality. Adherence to the MedDiet was measured by the relative Mediterranean score (rMED), and alcohol consumption by the Mediterranean Alcohol-drinking Pattern index (MADP). Statistical analyses included flexible parametric survival models and subdistribution hazard ratios, to consider different causes of death. a significant increase in digestive-system (SHR 2.77, 95% CI 1.16; 63) and cancer mortality risk (SHR 2.25, 95% CI 1.08; 4.70) was observed among individuals with low adherence to the MADP. Low adherence to the Mediterranean pattern of alcohol consumption, combined with low adherence to the MedDiet, was associated with higher overall mortality (HR 2.29, 95% CI 1.04, 5.04), and, in particular, with higher mortality from digestive system diseases (SHR 4.38, 95% CI 1.22, 15.8). This study suggests that deleterious effects of alcohol on mortality vary, depending on alcohol consumption patterns and dietary context. Higher adherence to the MedDiet appears to mitigate the adverse effects of moderate alcohol consumption, particularly for wine drinkers.

Utility of prescription-based comorbidity indices for predicting mortality among Australian men with prostate cancer

BackgroundDrug prescription registries has become an alternative data source to hospital admission databases for measuring comorbidities. However, the predictive validity of prescription-based comorbidity measures varies based on the population under investigation and outcome of interest. We aimed to determine which prescription-based index of comorbidity has most utility in Australian men with prostate cancer. MethodsWe studied 25,414 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked datasets. The Rx-Risk index, Chronic Disease Score (CDS), Drug Comorbidity Index (DCI) and Pharmaceutical Prescribing Profile (P3) with one year lookback period from prostate cancer diagnosis were evaluated. The predictive ability of each index to determine all-cause deaths within two and five years of prostate cancer diagnosis was compared using the c-statistic from flexible parametric survival models, adjusting for age, socioeconomic status and year of prostate cancer diagnosis. ResultsThe Rx-Risk index performed better in predicting two-year (c-statistic = 0.818) and five-year (c-statistic = 0.784) all-cause mortality than P3, CDS and DCI. Including comorbidity measures as continuous scores resulted in a better performance than including them as categories. Grouping scores into four categories (≤0, >0 - ≤1, >1 - ≤2, and >2) resulted in better performance and calibration than using fewer categories. ConclusionRx-Risk was validated in Australia and reflects Australian prescribing patterns. It showed better predictive performance for mortality in our study, with a modest improvement over P3, CDS and DCI. For research with prostate cancer populations, we recommend the use of drug-based comorbidity indices that have been validated in a similar population.

Long-term outcomes and prognostic factors of surgical treatment of peri-implantitis - A retrospective study.

To evaluate long-term outcomes and prognostic factors of non-reconstructive surgical treatment of peri-implantitis. One hundred forty-nine patients (267 implants) were surgically treated for peri-implantitis and followed for an average of 7.0 (SD: 3.6) years. The primary outcome was implant loss. Additional bone loss and surgical retreatment were secondary outcomes. Patient/implant characteristics, as well as clinical and radiographic parameters collected prior to initial surgery, were evaluated as potential predictors of implant loss. Flexible parametric survival models using restricted cubic spline functions were used; 5- and 10-year predicted rates of implant loss were calculated according to different scenarios. Fifty-three implants (19.9%) in 35 patients (23.5%) were lost during the observation period. Implant loss occurred after a mean period of 4.4 (SD: 3.0) years and was predicted by implant surface characteristics (modified surface; HR 4.5), implant length (HR 0.8 by mm), suppuration at baseline (HR 2.7) and disease severity (baseline bone loss: HR 1.2 by mm). Estimates of 5- and 10-year implant loss ranged from 1% (best prognostic scenario; initial bone loss <40% of implant length, turned implant surface and absence of suppuration on probing (SoP)) to 63% (worst prognostic scenario; initial bone loss ≥60% of implant length, modified implant surface and SoP) and from 3% to 89%, respectively. Surgical retreatment was performed at 65 implants (24.3%) in 36 patients (24.2%) after a mean time period of 4.5 (3.1) years. In all, 59.5% of implants showed additional bone loss, were surgically retreated or lost. Recurrence of disease is common following surgical treatment of peri-implantitis. The strongest predictor for implant loss was implant surface characteristics. Implant length as well as suppuration and disease severity at baseline were also relevant factors.

Including uncertainty of the expected mortality rates in the prediction of loss in life expectancy

PurposeThis study introduces a novel method for estimating the variance of life expectancy since diagnosis (LEC) and loss in life expectancy (LLE) for cancer patients within a relative survival framework in situations where life tables based on the entire general population are not accessible. LEC and LLE are useful summary measures of survival in population-based cancer studies, but require information on the mortality in the general population. Our method addresses the challenge of incorporating the uncertainty of expected mortality rates when using a sample from the general population.MethodsTo illustrate the approach, we estimated LEC and LLE for patients diagnosed with colon and breast cancer in Sweden. General population mortality rates were based on a random sample drawn from comparators of a matched cohort. Flexible parametric survival models were used to model the mortality among cancer patients and the mortality in the random sample from the general population. Based on the models, LEC and LLE together with their variances were estimated. The results were compared with those obtained using fixed expected mortality rates.ResultsBy accounting for the uncertainty of expected mortality rates, the proposed method ensures more accurate estimates of variances and, therefore, confidence intervals of LEC and LLE for cancer patients. This is particularly valuable for older patients and some cancer types, where underestimation of the variance can be substantial when the entire general population data are not accessible.ConclusionThe method can be implemented using existing software, making it accessible for use in various cancer studies. The provided example of Stata code further facilitates its adoption.

Predicting risk of endometrial cancer in asymptomatic women (PRECISION): Model development and external validation.

Develop an endometrial cancer risk prediction model and externally validate it for UK primary care use. Cohort study. The UK Biobank was used for model development and a linked primary (Clinical Practice Research Datalink, CPRD) and secondary care (HES), mortality (ONS) and cancer register (NRCAS) dataset was used for external validation. Women aged 45-60 years with no history of endometrial cancer or hysterectomy. Model development was performed using a flexible parametric survival model and stepwise backward selection aiming to minimise the Akaike information criterion. Model performance on external validation was assessed through flexible calibration plots, calculation of the expected to observed ratio and C-statistic and decision curve analysis. Endometrial cancer diagnosis within 1-10 years of the index date. Model development included 222 031 women (902 incident endometrial cancer cases) and external validation 3 094 371 women (8585 endometrial cancer cases). The final model (with equation provided) incorporated age, body mass index, waist circumference, age at menarche, menopause and last birth, hormone replacement, tamoxifen and oral contraceptive pill use, type 2 diabetes, smoking and family history of bowel cancer. It was well calibrated on external validation (calibration slope 1.14, 95% confidence interval [CI] 1.11-1.17, E/O 1.03, 95% CI 1.01-1.05), with moderate/good discrimination (C-statistic 0.70, 95% CI 0.69-0.70) and had improved net benefit compared with previously developed models. The Predicting risk of endometrial cancer in asymptomatic women model (PRECISION), using easily measurable anthropometric, reproductive, personal and family history, accurately quantifies a woman's 10-year risk of endometrial cancer. Its use could determine eligibility for primary endometrial cancer prevention trials and for targeted resource allocation in UK general practices.