Background Population Research Articles

Effects of prescreening for likelihood ratio approaches in the forensic identification of source problems

Source prescreening is a methodology where forensic examiners select samples that are similar to given trace evidence to represent the background population. This background evidence helps assign a value of evidence using a likelihood ratio or Bayes factor. A potential benefit of prescreening is a mitigation of effects from subpopulation structures within the alternative source population by isolating the relevant subpopulation. This paper examines the impact of prescreening before assigning evidence value. Extensive simulations with synthetic and real data, including trace element and fingerprint score examples, were conducted. The findings indicate that when the subpopulation structure is known, prescreening can provide an accurate evidence value in cases of subpopulation structures. The study suggests that prescreening can be beneficial, but the prescreening method and level should be transparently reported alongside the evidence value.

Patient-reported outcome was close to the Danish background population 6 months after non-surgical treatment of Neer 2-part surgical neck fractures: a prospective cohort study in patients aged 60 or above.

Neer 2-part surgical neck fractures are the most common displaced proximal humerus fractures. We aimed to evaluate patient-reported outcome in a consecutive series of older people receiving nonoperative treatment. This is a single-center prospective cohort study. We included patients aged 60 or above referred to a Danish university hospital. The preregistered protocol followed the recommendations from randomized trials. Patients were followed at the outpatient clinic at 2, 6, and 24 weeks. After 24 weeks, they were evaluated with Oxford Shoulder Score (OSS, 0-48, 48 best) and EuroQoL 5 dimensions, 3 levels (EQ-5D-3L, -0.624 to 1, 1 best). Clinical failure was defined as conversion to surgery or OSS ≤ 24. Population norms were reported to interpret the cohort data, but no formal statistical comparisons between historical cohorts were planned. We used descriptive statistics to report rates and proportions. For 36 months, 268 patients (mean age 76, 79% female) with Neer 2-part surgical neck fractures received non-surgical treatment. After excluding patients with concomitant fractures, dementia, or death, complete follow-up was available for 167 patients. 8 patients (3.0%) had surgery. The mean OSS was 37.2 (SD 8.1), which equals 78% of maximum shoulder function. The norm for the population of the same age and gender was 82%. The mean EQ-5D-3L score was 0.79 (SD 0.16), while the norm for the same-age population was 0.82. 16 (10%) had an OSS score of 24 or below. Non-surgical treatment in older people with Neer 2-part surgical neck fractures resulted after 6 months in patient-reported shoulder function and quality of life close to that of the Danish background population.

Bipolar disorder in people with HIV: A nationwide, population-based matched case-control and matched cohort study.

To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings. Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts. Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios (HRs) among PWH for bipolar disorder and receipt of lithium. We included 5322 PWH and 53,220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection (aOR: 1.9, 95% confidence interval (CI): 1.2-3.0), especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (HR: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder, but not to the same degree as PWH and not of receipt of lithium. Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.

Endometriosis, a prevalent disease, is associated with significant cardiac disease

Abstract Background Endometriosis, a chronic systemic gynecological disease affecting 10% of women in the reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiac outcomes are scarce. Further research is needed to address this gap in knowledge as highlighted by recent calls from the European Heart Journal. Purpose To examine the incidence of the following outcomes both as a composite and individually: 1) ischemic events, 2) arrhythmias, and 3) heart failure among women with endometriosis compared with the background population. Methods Using Danish nationwide registries, all women with a diagnosis of endometriosis (1977-2021) were identified and matched with women from the background population in a 1:4 ratio based on year of birth. The incidence of 1) ischemic heart disease and ischemic stroke, 2) arrhythmias (including atrial flutter/fibrillation), and 3) heart failure were examined and compared between women with and without endometriosis. Results After exclusion of women with ischemic events/arrhythmias/heart failure prior to index, 59,194 women with endometriosis and 238,352 matched controls were included (median age 37.1 years [IQR 29.8-44.4 years]). The women were followed for a median of 17 years and a maximum of 45 years. Overall, women with endometriosis were more comorbid and used more medications than their matched controls. The 40-year cumulative incidences of the composite outcome were 36.2% (95%CI 35.4-37.1%) and 30.2% (95%CI 29.8-30.7%) among women with and without endometriosis, whereas it were 23.8% (95%CI 23.0%-24.5%) and 18.8% (95%CI 18.5%-19.1%) for ischemic events, 20.1% (95%CI 19.4%-20.9%) and 17.2% (95%CI 16.8%-17.5%) for arrhythmias, and 7.5% (95%CI 7.0-8.0%) and 6.6% (95%CI 6.3-6.8%) for heart failure, respectively (Figure 1). The most common arrhythmia was atrial fibrillation/flutter constituting more than half of the events in both groups. In both unadjusted and adjusted analyses, women with endometriosis compared with controls had a significantly higher associated risks of the composite outcome (unadjusted HR 1.30 [95%CI 1.27-1.34], adjusted HR 1.29 [95%CI 1.25-1.32]), ischemic events (unadjusted HR 1.32 [95%CI 1.28-1.37], adjusted HR 1.31 [95%CI 1.26-1.35]), arrhythmias (unadjusted HR 1.25 [95%CI 1.20-1.30], adjusted HR 1.24 [95%CI 1.19-1.29]), and heart failure (unadjusted HR 1.07 [95%CI 1.01-1.14]), adjusted analysis (HR 1.05 [95%CI 0.98-1.12]). Conclusions Women with endometriosis have a higher associated long-term risk of significant cardiac outcomes compared with the background population. Despite the small relative differences, the high prevalence of endometriosis underscores the importance of these findings and emphasizes the need for enhanced understanding and prevention of its long-term cardiac outcomes.

Risk of cardiovascular disease in Hodgkin lymphoma patients

Abstract Background Cardiovascular diseases are recognized as some of the most common and problematic late complications to the treatment of Hodgkin lymphoma (HL). However, the anticipated risk is predominantly based on studies of patients treated several decades ago with treatment regimens considered outdated by todays standard. Purpose To describe the risk of cardiovascular disease in HL patients undergoing contemporary treatment regimens and comparing this risk to matched comparators. Methods A register-based cohort study including all Danish HL patients ≥18 years at diagnosis, treated with anthracycline-containing chemotherapy between 2000 and 2022. Index date was defined as date of HL diagnosis. Matching with comparators from the background population was performed in a 1:5 ratio on age, sex, and comorbidities. Patients and comparators with malignancy and/or heart disease prior to the index date were excluded. The primary outcome was a composite endpoint of cardiovascular diseases: heart failure, ischemic heart disease, diseases of the aortic-, mitral-, and tricuspid valve, constrictive pericarditis, cardiomyopathies, atrial and ventricular arrythmias, or any invasive procedures related to these diagnoses. Follow-up began at index date and ended upon event, relapse, death, emigration, or end of follow-up (December 31, 2022), whichever occurred first. The cause-specific cumulative incidence of the primary outcome was computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator. Exploratory multivariable Cox regression analyses were performed to identify risk factors for cardiovascular disease among patients with HL. Risk factors were adjusted for sex, age, and comorbidities. Results A total of 1,917 HL patients and 9,585 matched comparators were included. Median age at diagnosis was 39 years (interquartile range [IQR]: 27-56), 57% were male, and median follow-up time was 10.2 years (IQR: 5.3-15.5). The majority of patients were treated with ABVD (83%) and the estimated median cumulative anthracycline dose was 250 mg/m2 (IQR: 200-300). During the study period, 50% of patients received radiotherapy. The cause-specific cumulative incidence of the primary outcome was higher among HL patients compared with comparators across follow-up: 3.7% (95% confidence interval: 2.8-4.6) vs. 2.0% (95% CI: 1.7-2.3) at 5 years, 7.2% (95% CI: 5.7-8.7) vs. 4.6% (95% CI: 4.1-5.1) at 10 years, and 14.2% (95% CI 11.6-16.9) vs 6.7% (95% CI: 6.0-7.5) at 15 years (Figure 1). Risk factors associated with development of heart disease in HL patients were history of hypertension (HR=1.81, 95% CI 1.15-2.84) and male sex (HR=2.01, 95% CI 1.39-2.91) (Figure 2). Conclusions The long-term risk of cardiovascular disease is still high in patients with HL after contemporary treatment suggesting that the use of modern radiotherapy has not eliminated the excess risk of cardiovascular disease.

The 5-Item Modified Frailty Index (mFI-5) for risk stratification of patients with infective endocarditis undergoing cardiac surgery

Abstract Background population aging has led to an increased burden of frailty as an emerging global health issue, and variables for its quantification in patients with infective endocarditis (IE) are lacking in current surgical risks scores. The 5-item modified frailty index (mFI-5) score has shown to be effective in the prediction of surgical outcomes in other medical scenarios. Purpose this study aimed to assess the role of the mFI-5 in the prediction of surgical outcomes in patients with left-sided IE undergoing cardiac surgery. Methods a total of 112 cases of confirmed left-sided IE undergoing surgery, were consecutively collected and followed during one year after diagnosis in two tertiary hospitals between 2016 and 2021. The mFI-5 score included 5 baseline patient-specific comorbidities: diabetes, congestive heart failure, non-independent functional status (Barthel index <80), hypertension and chronic obstructive pulmonary disease (range 0-5), and patients were categorised as mFI-low (<2, n=65), and mFI-high (>=2, n=47). Results mean age was 66 [SD 15] years, 67% were men and community-acquired infections were 75%. As shown in Table 1, mFI-high patients were older and, aside from the specific comorbidities included in the score, with more chronic kidney disease. The most isolated pathogen was S. viridans (n=32), predominantly in mFI-low, in contrast to enterococcal and polymicrobial IEs, which were more frequent in mFI-high. Larger vegetations were reported in mFI-high [16 (10) vs 13 (9) mm, p 0.03], with no differences regarding infection site or periannular complications. Acute kidney injury, decompensated heart failure and higher natriuretic peptides were more common in mFI-high. Regarding mortality, in-hospital deaths were more frequent in mFI-high group. When analyzing mFI-score as a discrete variable, in-hospital mortality was associated with higher median scores values [2 (2) vs 1(1) points, p 0.02], being 2 points the optimal cutoff point for prediction [AUC 0.64 (95% CI 0.54-0.73), Fig.1A]. Among survivors who completed follow-up (n=82), rehospitalization and all-cause mortality rates in mFI-high exceeded those from mFI-low. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1B), confirming the independent prognostic association of mFI-5-score in patients with IE undergoing surgery. Conclusions patients with IE undergoing cardiac surgery with higher mFI-5 scores were older, more predisposed to enterococcal and polymicrobial infections, and had a greater comorbidity burden with a more complicated clinical course. The mFI-score was independently associated with in-hospital mortality as well as rehospitalizations and 1-year mortality, positioning itself as an additional tool for risk stratification in this cluster of patients.Table 1Figure 1

Population Health Management effectiveness in the primary healthcare setting: a systematic review

Abstract Background Population Health Management (PHM) has shown promise as a tool in the improvement of health at scale. It works by; harnessing health-related datasets, allowing for population segmentation and risk stratification, and targeting interventions to yield positive health impact. Prior reviews on PHM, have sought to define PHM and assess feasibility. To date, there have been no systematic reviews that assess the effectiveness of PHM in achieving some or all of the quintuple aims of PHM (WHO 2023). The aim of this study is to determine the value and impact of a PHM approach in managing ambulatory care sensitive conditions (ACSCs) in the primary healthcare setting. Methods This systematic review is underpinned by a Population-Intervention-Comparator-Outcome (PICO) framework. The PROSPERO-registered study commenced in February 2024 for papers published since January 2000. Pubmed, Cinahl and Web of Science databases were used. Titles and abstracts of studies were reviewed using agreed eligibility criteria to select studies for inclusion and risk of bias assessment. Data abstraction and synthesis determined the effectiveness of PHM against agreed outcome measures. Results The search yielded 427 articles of which 19 were included. Studies addressed diabetes, hypertension, atrial fibrillation, asthma and comorbid conditions. Nearly all studies were based in the U.S.A. Almost 50% of studies showed a significant improvement in health outcomes following PHM. Study features that corresponded with positive health outcomes included; the use of population management tools, the employment of disease/population health managers and the mobilisation of medication reviews/education. Conclusions The challenges facing communities and health services require an alternative innovative approach to health such as a PHM approach. The results of this study will inform a larger body of work which seeks to establish a PHM approach to the delivery of services in the Mid-West region of Ireland. Key messages • Population health management (PHM) could be a viable mechanism for health services to serve increasing need and multi-morbid populations. • This is the first systematic review of PHM against the quintuple aims of PHM, specifically in the management of ambulatory care sensitive conditions in primary healthcare.

Epidemiology and prognosis of obstructive and non-obstructive hypertrophic cardiomyopathy in Finland: a nationwide cohort study

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease. The Finnish population has a specific genetic background, which may influence and even predispose people to various hereditary diseases. Whilst advances in genetic testing and imaging techniques may have influenced the detection of HCM and associated subtypes, contemporary data on incidence and prevalence remain limited. Purpose This study aimed to evaluate the current trends in the incidence, prevalence, and prognosis of obstructive and non-obstructive HCM in a nationwide cohort in Finland. Methods A population-based registry study was conducted using data from Finnish nationwide healthcare registries (HILMO/avoHILMO) including individuals aged at least 12 years with recorded HCM diagnosis between 2000 and 2021. The incidence was calculated by dividing the number of newly diagnosed HCM patients by the Finnish background population. Furthermore, the mean incidence per age-group was calculated by dividing the sum of age-group specific incidences by the number of age groups. The date and cause of death were obtained from national registries (Statistics Finland). Mortality was computed by dividing the number of deaths by follow-up length. Patients were followed from 2014 to 2021, and incident cases were defined as new diagnoses after 2014. HCM cases were stratified into obstructive HCM and non-obstructive HCM based on ICD-10 codes I42.1 and I42.2, respectively. Results Among 5,834 documented patients with HCM, the overall mean incidence by age-group was 2.64/100,000, with incidence increasing with age, peaking in those aged ≥85 years (6.22/100,000 patient-years [PY]). Annual incidence of obstructive HCM decreased from 2.2 to 1.4/100,000 PY, while non-obstructive HCM increased from 4.6 to 5.4/100,000 PY between 2014 and 2021 (Fig 1). Prevalence of non-obstructive HCM rose from 40 to 56/100,000 PY, while obstructive HCM prevalence remained stable (23-24/100,000 PY). All-cause mortality was 5.5/100 PY, with obstructive and non-obstructive HCM mortality at 5.7 and 4.6/100 PY, respectively. HCM-specific deaths accounted for 16% and 12% of all deaths in patients with non-obstructive and obstructive HCM, respectively. Conclusions This nationwide study in Finland revealed an increasing incidence and prevalence of non-obstructive HCM over time, contrasting with stable rates among patients with obstructive HCM. Incidence and prevalence were strongly age dependent. Non-HCM-related deaths were predominant in both HCM subtypes.

Research on Corps University Students' Awareness and Attitudes Toward the Consciousness of the Chinese National Community

In the context of globalization and multi-ethnic backgrounds in the new era, cultivating the consciousness of the Chinese national community is particularly important. This paper focuses on Corps university students, exploring their awareness and attitudes towards the Chinese national community consciousness through surveys and analysis. Corps universities, as higher education institutions managed by the Xinjiang Production and Construction Corps, provide rich material for this study due to their unique social background and diverse student population. The study finds that most students hold a positive attitude towards the Chinese national community, but there are variations in their sense of identification, participation, and cultural recognition. Factors influencing students' attitudes include personal background, educational experience, social environment, and policy promotion. The paper suggests optimizing educational content, enhancing cultural exchanges, and strengthening policy promotion to improve students' consciousness of the Chinese national community. The research results provide a reference for relevant policy formulation and implementation and lay a foundation for further research.

Epilepsy adverse events post vaccination

Aim: Seizure and epilepsy adverse events (AEs) can occur following vaccination. For epilepsy AEs, they are generally expected to only occur at background population frequencies without associations with immunizations. The Vaccine AEs Reporting System (VAERS) collects a subset of AEs experienced by vaccinees, including multiple epilepsy related AEs. This study examines the possibility of immunization associated epilepsy AEs in VAERS occurring above background rates. Methods: Herein, VAERS is retrospectively examined for epilepsy and seizure AEs following immunizations (AEFIs). Reported AEFIs are normalized by total AEFIs for each vaccine. VAERS data is examined by vaccine type, vaccine source, vaccinee gender, and age-stratified for infants. Results: Association signals for examined epilepsy and seizure AEFIs are identified for multiple vaccines when compared to other vaccines with normalized frequencies above expected population background frequencies. Normalized epilepsy AEFI frequencies for children less than 1 year are higher than children aged 1 year for several vaccines. For pairs of matched vaccines from different manufacturers, statistically different epilepsy AEFI normalized frequencies were observed. These matched pairs for multiple vaccines implicate likely vaccine contaminations (e.g., endotoxins) as likely candidates for causing elevated epilepsy and seizure AEFIs. Conclusions: Based on the reported results, delaying some immunizations of a small set of vaccines until children are 1 year of age is predicted to reduce epilepsy AEFI occurrences for these vaccines. For several vaccines, statistically significant differences in epilepsy AEFI normalized frequencies were detected for the same (or similar) vaccine from different manufacturers; this suggests that possible manufacturing contaminant(s) (e.g., endotoxins) as the likely causative agent(s) for observed epilepsy AEFIs above background rates. Eliminating or reducing these possible contaminants is predicted to reduce the observed associations closer to background population levels observed for other vaccines with very low epilepsy AEFI normalized frequencies.

Congenital heart diseases

During the last decades, the prognosis for patients with congenital heart disease (CHD) has gone through a tremendous development due to improvement in diagnostic tools, treatment, and follow-up. This has resulted in a demographic change of the population with CHD so that the number of adults exceeds that of paediatric patients. The improved survival has led to new challenges including re-interventions addressing residual lesions as well as long-term complications such as arrhythmia and heart failure. This has resulted in the development of novel catheter-based interventions e.g. percutaneous valve implantation, pulsed-field ablation, and lymphatic procedures as summarised in this review. Despite this, further developments are needed since morbidity and mortality are still significantly increased in patients with CHD compared to the background population.

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women- a case-control study.

To investigate bone mineral density (BMD), osteoporosis prevalence and systemic sclerosis (SSc) specific associations of BMD in SSc patients compared with background population. In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 respectively) and 505 age and sex matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by Dual-energy X-ray absorptiometry. Osteopenia was defined as T-score -1.0 to -2.5; osteoporosis as T-score ≤-2.5. Associates of low BMD were identified by multiple regression analysis. Women with SSc had lower BMD for total hip (p< 0.001) and spine (p= 0.011), equivalent to ΔT-score -0.56 and -0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (p= 0.001, compared with controls). Already in women below age 45, differences in hip BMD were apparent (ΔT-score -0.93, p= 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (p= 0.009) and diffuse skin involvement (p= 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age matched counterparts. SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasizes the importance of performing bone health assessment of all SSc patients, including men and young subjects.

9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. BACKGROUND AND OBJECTIVE: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &amp;gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &amp;gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &amp;gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. BACKGROUND AND OBJECTIVE: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &amp;gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Comparison of mortality in crohn’s disease patients complicated by intestinal failure with background population and with Crohn’s disease patients without intestinal failure

Comparison of mortality in crohn’s disease patients complicated by intestinal failure with background population and with Crohn’s disease patients without intestinal failure

Epidemiological comparison of emergency department presentations with seasonal influenza or COVID-19 and an outcome of intensive care admission or death: A population-based records linkage study in New South Wales, Australia

COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection. De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death). Influenza infection was notified in 2335 and COVID-19 in 5053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period. The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.

Social behaviour mediates the microbiome response to antibiotic treatment in a wild mammal.

High levels of social connectivity among group-living animals have been hypothesized to benefit individuals by creating opportunities to rapidly reseed the microbiome and maintain stability against disruption. We tested this hypothesis by perturbing the microbiome of a wild population of Grant's gazelles with an antibiotic and asking whether microbiome recovery differs between individuals with high versus low levels of social connectivity. We found that after treatment, individuals with high social connectivity experienced a faster increase in microbiome richness than less socially connected individuals. Unexpectedly, the rapid increase in microbiome richness of highly connected individuals that received treatment led to their microbiomes becoming more distinct relative to the background population. Our results suggest that the microbiome of individuals with high social connectivity can be rapidly recolonized after a perturbation event, but this leads to a microbiome that is more distinct from, rather than more similar to the unperturbed state. This work provides new insight into the role of social interactions in shaping the microbiome.