Cumulative Incidence Proportions Research Articles

Mortality related to left ventricular ejection fraction and obstructive coronary artery disease in non-ST-segment elevation myocardial infarction

Abstract Background Extent of coronary artery disease (CAD) and the severity of reduced left ventricular ejection fraction (LVEF) have both been associated with the prognosis after non-ST-segment elevation myocardial infarction (NSTEMI). However, the contemporary mortality associated with the extent of obstructive CAD over a range of LVEF remains uncertain. Purpose The aim of this study was to assess the impact of CAD and LVEF on all-cause death following a first-time NSTEMI. Methods We included consecutive first-time NSTEMI patients undergoing coronary angiography from 2010 to 2021 in Western Denmark. Patients were stratified by extent of obstructive vessel disease (VD; 1, 2, or 3VD) and LVEF (≥51%, 41-50%, or 10-40%). Patients with previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting were excluded. The primary outcome was all-cause death. We calculated 5-year cumulative incidence proportions (CIP) as a measure of absolute risk and adjusted hazard ratios (HR). Results A total of 8,770 patients with first-time NSTEMI and obstructive CAD were examined with coronary angiography. Two-thirds were male and median age was 68 years (Q1-Q3: 58-78). The increase in mortality associated with decreasing LVEF was greater than observed by extent of CAD (Table). Thus, the 5-year mortality increased stepwise by extent of CAD from 14% for 1VD to 31% for 3VD (adjusted HR 1.35, 95% CI:1.19-1.54), but from 12% for LVEF ≥51% to 40% for LVEF 10-40% (adjusted HR 2.32, 95% CI: 2.04-2.65). When combining LVEF and extent of CAD, an increase in 5-year mortality was found from 9% for 1VD and LVEF ≥51% to 46% for 3VD and LVEF 10-40% (risk difference of 37.1%; Figure). Correspondingly, using 1VD and LVEF ≥51% as reference, the adjusted HRs increased gradually with extent of CAD and decline in LVEF to 3.05 (95% CI: 2.51-3.70) for patients with 3VD and LVEF 10-40% (Table). Conclusion In a contemporary all-comers cohort of first-time NSTEMI patients, increasing extent of CAD and declining LVEF are both associated with a gradual increase in 5-year mortality. Our data suggest that the level of LVEF reduction was more strongly associated with 5-year mortality than CAD extent.

Retrospective review of the toxicities and change in dosing patterns for pegaspargase in patients with acute lymphoblastic leukemia/lymphoma and T-cell lymphoma.

Pegaspargase (PEG) is a key component of standard regimens for acute lymphoblastic leukemia/lymphoma (ALL) and extranodal natural killer/T-cell lymphoma (NKTCL). Emerging evidence suggests an opportunity to decrease incidence of PEG-associated toxicities with dose capping, but evidence is limited. This study aims to evaluate whether a significant difference in PEG-associated toxicities related to dosing strategy exists and to identify patient-specific or regimen-specific factors for PEG-related toxicity. A retrospective analysis of PEG-associated toxicities was completed in adult patients with ALL or NKTCL who received PEG within Cancer and Leukemia Group B (CALGB) 10403 or modified dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide (mSMILE) regimens at the UW Medical Center/Fred Hutchinson Cancer Center. PEG-associated toxicities that occurred through 8 weeks after PEG doses were noted. Twenty-eight patients received dose-capped PEG, and 29 received noncapped PEG. Fewer all-grade and grade 3/4 toxicities were observed in the dose-capped cohort. Grade 3/4 toxicities observed were hepatotoxicity, hyperglycemia, hypersensitivity, and hypertriglyceridemia. In addition, fewer grade 3/4 pancreatitis and thrombosis events occurred in the dose-capped cohort. Hypertriglyceridemia and hepatotoxicity were associated with the highest cumulative incidence proportions among all toxicities. Dose capping of PEG was associated with a similar or later median onset for most toxicities, a less heterogeneic toxicity profile, and a lower recurrence of most toxicities upon PEG rechallenge compared to the non-dose-capped cohort. Standardizing PEG dose capping in the CALGB 10403 and mSMILE regimens may translate to improved tolerance compared to a historical standard of no dose capping PEG.

Risk of a post-colonoscopy colorectal cancer in patients with diverticular disease: a population-based cohort study.

Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 30% of all colorectal cancers (CRCs) diagnosed in patients with diverticular disease; however, absolute and relative risks of PCCRC among these patients undergoing colonoscopy remain unknown. We performed a cohort study (1995-2015) including patients with and without diverticular disease who underwent colonoscopy. We calculated 7-36-month cumulative incidence proportions (CIPs) of PCCRC. We used Cox proportional hazards regression models to compute hazard ratios (HRs) of PCCRC, comparing patients with and without diverticular disease, as a measure of relative risk. We calculated 3-year PCCRC rates, as per World Endoscopy Organization recommendations, to estimate the proportion of CRC patients with and without diverticular disease who were considered to have PCCRC. We stratified all analyses by PCCRC location. We observed 373 PCCRCs among 56 642 patients with diverticular disease and 1536 PCCRCs among 306 800 patients without diverticular disease. The PCCRC CIP after first-time colonoscopy was 0.45% (95%CI 0.40%-0.51%) for patients with and 0.36% (95%CI 0.34%-0.38%) for patients without diverticular disease. Comparing patients with and without diverticular disease undergoing first-time colonoscopy, the adjusted HR was 0.84 (95%CI 0.73-0.97) for PCCRC and 1.23 (95%CI 1.01-1.50) for proximal PCCRCs. The 3-year PCCRC rate was 19.0% (22.3% for proximal PCCRCs) for patients with and 6.5% for patients without diverticular disease. Although the absolute risk was low, the relative risk of proximal PCCRCs may be elevated in patients with diverticular disease undergoing colonoscopy compared with patients without the disease.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study

Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

The one-year infection risk among patients diagnosed with giant cell arteritis: use of antibiotics and hospitalisations

Abstract Objectives Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA. Methods This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996–2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD) and relative risks (RR) of infections. Results The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7–53.2) for overall infections and 17.6% (95% CI: 17.1–18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38–1.42) for overall infections and 2.71 (95% CI: 2.61–2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years) and higher comorbidity were associated with an increased risk of infections among patients with GCA. Conclusions The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk.

Genetic risk, modifiable risk factors, and atrial fibrillation in the Danish diet, cancer, and health cohort

Abstract Background The etiology of AF is multifactorial. Genetic susceptibility and lifestyle contribute to atrial fibrillation (AF) risk.(1,2) However, the relationship between combined genetic predisposition and lifestyle risk factors on AF risk is unclear. Purpose We aimed to assess a possible interaction between modifiable risk factors and genetics on AF risk. Methods We included AF cases and a randomly drawn subcohort of 4,040 participants from the Danish Diet, Cancer, and Health study. Modifiable risk factors were assessed including smoking, body mass index, physical activity, diet, alcohol consumption, total cholesterol, and blood pressure. Based on cumulation of risk factors, a risk factor profile was determined for all participants and categorized as poor, intermediate, and ideal. Based on DNA sequence polymorphisms, we calculated a genetic risk score for AF, and categorized participants as having a low (quintile 1), intermediate (quintile 2-4) or high (quintile 5) genetic risk. Diagnoses of AF and/or atrial flutter were obtained from the Danish National Patient Register. We used weighted Cox proportional hazards regression to assess hazard ratios of AF. Results 3,094 AF cases occurred during a median follow-up of 12.9 years. Median age at baseline in the subcohort was 55 years (25th-75th percentile 52-60) and 2,092 (55%) were women. Participants at intermediate and high genetic risk had higher rates of AF compared with those at low genetic risk. Likewise, intermediate, and poor risk factor profiles were associated with higher rates of AF compared with those having ideal risk factor profiles. Weighted cumulative incidence proportions and hazard ratios of AF according to genetic risk and modifiable risk factors are shown in Figure 1. Within each category of genetic risk, incidence rates per 1,000 person-years were gradually higher with worse modifiable risk factor profiles. (Figure 2). For participants with high genetic risk, the incidence rates of AF per 1,000 person years were 5.0 (95% CI 3.4-7.3) for ideal, 6.6 (95% CI 5.4-8.1) for intermediate, and 10.4 (95% CI 9.2-11.8) for poor risk factor profiles. On an additive scale, there was a statistically significant interaction between genetic risk and modifiable risk factors (relative excess risk due to interaction=0.86 (95% 0.68-1.03, p<0.001). Conclusions A genetic risk score and modifiable risk factors were each associated with AF risk. The rates of AF increased gradually with cumulation of modifiable risk factors within each category of the genetic risk score, and we found an additive interaction between genetic risk and the modifiable risk factor profile. This underlines the importance of risk factor modification in primary AF prevention.Figure 1Figure 2

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells.

To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. Of 341 women, 134 (39.3%) had CIN 3-AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0-97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47-5.00 and HR 3.41, 95% CI 1.95-5.96, respectively). Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Risk Levels and Adverse Clinical Outcomes Among Patients With Nonvalvular Atrial Fibrillation Receiving Oral Anticoagulants

The CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group. This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. Initiation of oral anticoagulants. We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends. The observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Atypical glandular cells and development of cervical cancer: Population-based cohort study.

The effect of cervical screening on cervical adenocarcinoma has been variable, possibly because the risk associated with the precursor atypical glandular cells (AGC) is not well known. A cohort of all 885 women in the capital region of Sweden with AGC, a concomitant human papillomavirus (HPV) analysis, and a histopathology was followed until 2019. Cumulative incidence proportions of cervical intraepithelial lesion grade 3 or worse (CIN3+) by HPV type was determined by 1-Kaplan-Meier estimates. Hazard ratios (HR) for CIN3+ or for invasive cancer were estimated with Cox regression. After 2 years of follow-up, the cumulative incidence proportions of CIN3+ were 80% (95% confidence interval [CI]: 74-86%), 58% (95% CI: 50-60%) and 10% (95% CI: 5-18%) among HPV16/18 positive, "other HPV" positive and HPV-negative women, respectively. Among the 300 women with HPV16/18 positive AGC, 217 developed CIN3+ of which 35 were invasive cervical cancer. The 2-year cumulative invasive cancer risk for HPV16/18 positive AGC was 17% (95% CI: 12-24%). Primary HPV-screening had a similar yield of CIN3+ as cytology screening, albeit HPV-negative AGC is by design not detected by HPV screening. Among 241 women with HPV-negative AGC, 11 developed CIN3+ mostly after clinically indicated samples. We found no significant risk differences depending on age or sampling indication. The low CIN3+ risk after HPV-negative AGC implies safety of primary HPV screening. The high risk of invasive cervical cancer after HPV16/18 positive AGC implies that management of this finding is a priority in cervical screening.

A nationwide study of ocular manifestations leading to hospital contacts among patients with giant cell arteritis

ObjectivesTo investigate the risk of ocular manifestations leading to hospital contacts among patients with giant cell arteritis (GCA). MethodsA Danish, nationwide, register-based cohort study including 14,574 GCA patients diagnosed 1996–2018 and 145,740 general population referents, matched on sex and date of birth. Cumulative incidence proportions (CIPs) and relative risks (RRs) of ocular manifestations with 95% confidence intervals (CIs) were calculated using a pseudo-observation approach. ResultsA total of 1026/14,574 (7.0%) GCA patients were registered with ocular manifestations within ±1 year of the diagnosis; 392/1026 (38%) being before and 634/1026 (62%) after the GCA diagnosis, and 744/1026 (73%) were registered within ±1 month of the diagnosis. The diagnoses were 336/1026 (33%) retinal vascular occlusions, 300/1026 (29%) disorders of the optic nerve, 177/1026 (17%) visual impairment, 90/1026 (9%) diplopia, and 123/1026 (12%) amaurosis fugax. The CIP for ocular manifestations among GCA patients after 3, 6, and 12 months following the diagnosis were 4.0% (95% CI: 3.6–4.3), 4.2% (95% CI: 3.9–4.6), and 4.6% (95% CI: 4.2–4.9). The 1-year RR of ocular manifestations among GCA patients was 28.0 (95% CI: 24.0–32.7), with age above 70 years, male sex, and a positive temporal artery biopsy being risk factors. Treatment with low-dose aspirin was not associated with a reduced 1-year RR of incident ocular manifestations. ConclusionsIn GCA, most cases of ocular manifestations leading to hospital contacts occur close to the time of diagnosis, with over one-third of cases occurring before the diagnosis, emphasizing the need for early recognition and treatment.

Risk of dementia in patients with inflammatory bowel disease: a Danish population-based study.

SummaryBackgroundInflammatory bowel disease (IBD) may be associated with increased dementia risk, but the literature is conflicting.AimTo investigate dementia risk in patients with IBD.MethodsWe conducted a nationwide population‐based cohort study in Denmark (1977–2018) including all patients with incident IBD matched with up to 10 general population comparators without IBD by sex, year of birth and region of residence. We calculated cumulative incidence proportions (CIPs) of dementia treating death as a competing risk, and adjusted hazard ratios (HRs) comparing IBD patients with matched comparisons. In a nested case–control analysis, we investigated the impact of IBD severity, steroid use, colorectal and small bowel surgery, and healthcare system contacts on dementia risk.ResultsOf 88,985 patients with IBD (69.6% with ulcerative colitis [UC], 30.4% with Crohn's disease [CD]) and 884,108 comparisons, 2076 patients (78.1% with UC) and 23,011 comparisons (76.6% UC comparisons) developed dementia. The 40‐year CIP of all‐cause dementia was 7.2% for UC patients and 5.8% for CD patients. UC patients had a slightly increased HR of all‐cause dementia (HR = 1.07 [95% confidence interval (CI): 1.01;1.12]) and Alzheimer's disease (HR = 1.10 [95% CI: 1.01–1.19]). CD patients had an increased HR of all‐cause dementia (HR = 1.15 [95% CI: 1.05–1.27]) and frontotemporal dementia (HR = 2.70 [95% CI: 1.44–5.05]). Dementia in IBD patients was associated with frequent healthcare system contacts.ConclusionsUC and CD are associated with slightly increased all‐cause dementia risk, particularly frontotemporal dementia in CD patients. Frequent healthcare system contacts by patients with IBD and detection bias may play a role in the association.

Abstract P3-12-22: Socioeconomic position and prognosis in premenopausal breast cancer: A population-based cohort study in Denmark

Abstract Background: To investigate how socioeconomic position (SEP) influences the effectiveness of cancer-directed treatment in premenopausal breast cancer patients in terms of breast cancer recurrence and mortality.Methods: Our cohort included all premenopausal women aged 18-55 years diagnosed with non-metastatic breast cancer and prescribed docetaxel-based chemotherapy in Denmark during 2007-2011. Population-based administrative registries provided data on SEP: marital status (married including registered partnership or single including divorced or widowed), cohabitation (cohabiting or living alone), education (low, intermediate or high), income (low, medium or high), and employment status (employed, unemployed or health-related absenteeism). For each SEP measure, we computed incidence rates, cumulative incidence proportions (CIPs) and used Poisson regression to compute incidence rate ratios and 95% confidence intervals (95% CIs) of recurrence and death. We stratified on ER status/tamoxifen to evaluate interaction.Results: Our cohort included 2,616 women; 286 (CIP: 13%) experienced recurrence and 223 (CIP: 11%) died during follow-up (median 6.6 and 7.2 years, respectively). Single women had both increased risks of recurrence (IRR: 1.45, 95% CI: 1.11-1.89) and mortality (IRR: 1.83, 95% CI: 1.32-2.52). Furthermore, we observed increased mortality in women with low education (IRR: 1.49, 95% CI: 0.95-2.33), low income (IRR: 1.37, 95% CI: 0.83-2.28), unemployment (IRR: 1.61, 95% CI: 0.83-3.13) or health-related work absenteeism (IRR: 1.80, 95% CI: 1.14-2.82), but smaller or no increased risk of recurrence. These findings were especially evident among women with ER+ tumors prescribed tamoxifen.Conclusions: Low SEP in premenopausal women with non-metastatic breast cancer was associated with increased mortality, but not always recurrence. This suggests underdetection of recurrences in certain groups. Poor prognosis in women with low SEP, especially single women, may partly be explained by tamoxifen adherence. Citation Format: Cathrine Hjorth, Per Damkier, Bent Ejlertsen, Timothy L Lash, Henrik T Sørensen, Deirdre Cronin-Fenton. Socioeconomic position and prognosis in premenopausal breast cancer: A population-based cohort study in Denmark [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-22.

Abstract P3-13-06: Single nucleotide polymorphisms and mortality after docetaxel-based chemotherapy in premenopausal breast cancer: A population-based cohort study in Denmark

Abstract Background Taxane-based chemotherapy is first line treatment in various cancers, including premenopausal breast cancer, but the inter-individual effectiveness is unpredictable. Differences in expression and activity of docetaxel-metabolizing enzymes and transporters (DMETs) may modify docetaxel effectiveness. Although reported data are inconsistent, some findings suggests that variant alleles that reduce the function of 1) SLC-transporters reduce drug influx into hepatocytes; 2) CYP-450 enzymes hamper drug metabolism; and 3) ABC-transporters decrease docetaxel clearance. The net effect is hypothesized to be increased docetaxel exposure and effectiveness. In contrast, GSTP1 variants have been associated with poorer docetaxel effectiveness. We investigated whether single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes and transporters were associated with mortality in premenopausal breast cancer patients. Materials and methods Using the Danish Breast Cancer Group (DBCG) clinical database, we identified data on premenopausal women aged 18–55 years, diagnosed with non–metastatic breast cancer during 2007–2011. All women were recommended epirubicin, cyclophosphamide and docetaxel-based adjuvant chemotherapy, and tamoxifen if the disease was estrogen receptor (ER) positive. From DBCG and other Danish administrative and medical registries we retrieve data on death, emigration, and tumor characteristics. We collected archived formalin-fixed paraffin-embedded primary tumor tissue from Danish pathology departments. We genotyped 17 candidate SNPs using TaqMan SNP genotyping assays and, for each SNP, categorized the women as having two normal alleles (wildtype) or at least one variant allele. We followed the women from six months after breast cancer diagnosis until death, emigration or 30th June 2019, whichever came first. Comparing variant carriers with wildtype, we computed cumulative incidence proportions (CIPs) and used Poisson regression models to calculate unadjusted incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) of all–cause mortality. We stratified by ER status to evaluate interaction. Analyses were repeated for breast cancer specific mortality. Results Our cohort included 2,262 women. During follow–up (median 9.6 years, interquartile range: 8.4–11.0), 250 women died (CIP: 14%); 219 due to breast cancer (CIP: 11%). Genotyping was successful for ≥95% of the study cohort, with exception of two SNPs, which were excluded from analyses. We detected decreased mortality in variant carriers of SLCO1B1 rs2306283 (IRR: 0.75, 95% CI 0.58–0.97), and ABCB1 rs1128503 (IRR: 0.81, 95% CI: 0.63–1.05), ABCB1 rs2032582 (IRR: 0.80, 95% CI: 0.62–1.04) and ABCC2 rs12762549 (IRR: 0.80, 95% CI: 0.62–1.04). In contrast, mortality was increased in carriers of GSTP1 rs1138272 (IRR: 1.28, 95% CI: 0.93–1.76) and, unexpectedly, in carriers of CYP3A rs10273424 (IRR: 1.36, 95% CI: 0.99–1.86) variant carriers. Sensitivity analyses yielded similar findings. ER status did not modify the associations. Conclusions In this study, mortality may be associated with SNPs in ABCB1, ABCC2, SLCO1B1, CYP3A and GSTP1 in premenopausal women with non-metastatic breast cancer receiving docetaxel. The mechanisms underlying our findings remains unclear but may be related to docetaxel pharmacokinetics. Citation Format: Cathrine F Hjorth, Per Damkier, Tore B Stage, Søren Feddersen, Bent Ejlertsen, Timothy L Lash, Stephen Hamilton-Dutoit, Thomas P Ahern, Mikael Rørth, Henrik T Sørensen, Deirdre Cronin-Fenton. Single nucleotide polymorphisms and mortality after docetaxel-based chemotherapy in premenopausal breast cancer: A population-based cohort study in Denmark [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-13-06.

Risk of a post-colonoscopy colorectal cancer in patients with type 2 diabetes: a Danish population-based cohort study

ObjectivePrevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the...

Increased risk of thoracic aortic complications among patients with giant cell arteritis: a nationwide, population-based cohort study.

To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA. In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk. We included 9908 GCA patients and 98204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4-2.2), 1.0% (0.7-1.2) and 4.8% (4.2-5.3). Compared with the referents, the 15-year RR were 11.2 (7.41-16.9) for thoracic AA, 6.86 (4.13-11.4) for AD, 1.04 (0.83-1.32) for abdominal AA and 1.53 (1.35-1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4-11.2) with a number needed to be screened of 250 (167-333), 91 (71-111) and 53 (45-67) after 5, 10 and 15 years. Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA.

ICD shocks and complications in patients with inherited arrhythmia syndromes.

BackgroundThere is limited information on the long-term outcomes of ICDs in patients with inherited arrhythmia syndromes.MethodsProspective registry study of inherited arrhythmia patients with an ICD. Incidence of therapies and complications were measured as 5-year cumulative incidence proportions and analyzed with the Kaplan-Meier method. Incidence was compared by device indication, diagnosis type and device type. Cox-regression analysis was used to identify predictors of appropriate shock and device complication.Results123 patients with a mean follow up of 6.4 ± 4.8 years were included. The incidence of first appropriate shock was 56.52% vs 24.44%, p < 0.05 for cardiomyopathy and channelopathy patients, despite similar ejection fraction (61% vs 60%, p = 0.6). The incidence of first inappropriate shock was 13.46% vs 56.25%, p < 0.01 for single vs. multi-lead devices. The incidence of first lead complication was higher for multi-lead vs. single lead devices, 43.75% vs. 17.31%, p = 0.04. Patients with an ICD for secondary prevention were more likely to receive an appropriate shock than those with primary prevention indication (HR 2.21, CI 1.07–4.56, p = 0.03). Multi-lead devices were associated with higher risk of inappropriate shock (HR 3.99, CI 1.27–12.52, p = 0.02), with similar appropriate shock risk compared to single lead devices. In 26.5% of patients with dual chamber devices, atrial sensing or pacing was not utilized.ConclusionThe rate of appropriate therapies and ICD complications in patients with inherited arrhythmia is high, particularly in cardiomyopathies with multi-lead devices. Risk-benefit ratio should be carefully considered when assessing the indication and type of device in this population.

Socioeconomic position and prognosis in premenopausal breast cancer: a population-based cohort study in Denmark

BackgroundTo investigate how socioeconomic position (SEP) influences the effectiveness of cancer-directed treatment in premenopausal breast cancer patients in terms of breast cancer recurrence and mortality.MethodsWe conducted a cohort study nested in the ProBeCaRe (Predictors of Breast Cancer Recurrence) cohort (n = 5959). We identified all premenopausal women aged 18–55 years diagnosed with non-metastatic breast cancer and prescribed docetaxel-based chemotherapy in Denmark during 2007–2011. Population-based administrative registries provided data on SEP: marital status (married including registered partnership or single including divorced or widowed), cohabitation (cohabiting or living alone), education (low, intermediate, or high), income (low, medium, or high), and employment status (employed, unemployed, or health-related absenteeism). For each SEP measure, we computed incidence rates, cumulative incidence proportions (CIPs), and used Poisson regression to compute incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of recurrence and death. We stratified on estrogen receptor (ER) status/tamoxifen to evaluate interaction.ResultsOur study cohort included 2616 women; 286 (CIP 13%) experienced recurrence and 223 (CIP 11%) died during follow-up (median 6.6 and 7.2 years, respectively). Single women had both increased 5-year risks of recurrence (IRR 1.45, 95% CI 1.11–1.89) and mortality (IRR 1.83, 95% CI 1.32–2.52). Furthermore, we observed increased 5-year mortality in women with low education (IRR 1.49, 95% CI 0.95–2.33), low income (IRR 1.37, 95% CI 0.83–2.28), unemployment (IRR 1.61, 95% CI 0.83–3.13), or health-related work absenteeism (IRR 1.80, 95% CI 1.14–2.82), but smaller or no increased risk of recurrence. These findings were especially evident among women with ER+ tumors prescribed tamoxifen. Overall analyses (follow-up max. 10 years) provided similar results.ConclusionsLow SEP in premenopausal women with non-metastatic breast cancer was associated with increased mortality, but not always recurrence. This suggests underdetection of recurrences in certain groups. Poor prognosis in women with low SEP, especially single women, may partly be explained by tamoxifen adherence.

Risk of a post-colonoscopy colorectal cancer diagnosis in patients with inflammatory bowel disease: a population-based cohort study.

BACKGROUND : Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 50 % of all colorectal cancers (CRCs) diagnosed in patients with inflammatory bowel disease (IBD). This may reflect a high colonoscopy frequency; however, evidence remains limited. METHODS : We conducted a cohort study of IBD and non-IBD patients undergoing colonoscopy. We calculated cumulative incidence proportions (CIPs) of PCCRC at 7-36 months after first-time and subsequent colonoscopies. We also computed crude and adjusted hazard ratios (HRs) of PCCRC, comparing IBD with non-IBD patients undergoing first-time and subsequent colonoscopies. Separate analyses were conducted for consecutive colonoscopies. We calculated 3-year rates of PCCRC to estimate the proportion of IBD and non-IBD CRC patients experiencing PCCRC. RESULTS : We observed 138 and 1909 PCCRCs among 34 688 IBD and 358 217 non-IBD patients who underwent colonoscopy. The CIP of PCCRC after first-time colonoscopy was 0.21 % (95 % confidence interval [CI] 0.17 %-0.27 %) for IBD patients and 0.37 % (95 %CI 0.35 %-0.39 %) for non-IBD patients. The adjusted HR of PCCRC after a first-time colonoscopy was 0.96 (95 %CI 0.75-1.22) and the adjusted HRs after subsequent colonoscopies had point estimates around 1.0. The 3-year PCCRC rate was 24.3 % (95 %CI 20.4 %-28.7 %) for IBD and 7.5 % (95 %CI 7.2 %-7.8 %) for non-IBD patients. CONCLUSIONS : Although PCCRCs accounted for a substantial proportion of all IBD-related CRCs, IBD patients had a low CIP of PCCRC. The elevated 3-year PCCRC rates may, among other factors, stem from the increased colonoscopy frequency in IBD patients.

Municipal return to work management in cancer survivors: a controlled intervention study

Introduction Resuming work during or after cancer treatment has become an important target in cancer rehabilitation. Purpose The aim was in a controlled trial to study the return to work (RTW) effect of an early, individually tailored vocational rehabilitation intervention targeted to improve readiness for RTW in cancer survivors. Material and methods Participants diagnosed with breast, cervix, ovary, testicular, colon-rectal, and head-and-neck cancers as well as being employed were allocated to a vocational rehabilitation intervention provided by municipal social workers (n = 83) or to usual municipal RTW management (n = 264). The intervention contained three elements: motivational communication inspired by Acceptance and Commitment Therapy by which RTW barriers were addressed, municipal cancer rehabilitation and finally employer and workplace contact. RTW effect was assessed as relative cumulative incidence proportions (RCIP) in the control and intervention group within 52 weeks of follow-up, estimated from the week where treatment ended at the hospital. RCIP was interpreted and reported as relative risk (RR) with 95% confidence intervals (CI) adjusted for gender, age cancer diagnosis, education, comorbidity, and sick leave weeks. Results Across cancer diagnoses 69 (83.1%) and 215 (81.4%) returned to work in the intervention and control group, respectively. No statistical effect was seen (RR 1.08 (95% CI 0.98–1.19)). Repeating the analyses solely for participants with breast cancer (n = 290) showed a significant effect of the intervention (RR 1.12 (95% CI 1.01–1.23)). Conclusion More than 80% returned to work in both groups. However, no statistical difference in RTW effect was seen across cancer diagnoses within one year from being exposed to an early, individually tailored vocational rehabilitation intervention compared with usual municipal RTW management. Trial registration number ISRCTN50753764