Relative Risk Of Death Research Articles

Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Priority directions for preserving the health of underground coal mining workers

Introduction. An increase in life expectancy, a decrease in the mortality rate of the working-age population and an extension of working longevity are the most important components in the development of the human potential of the Russian Federation. We observe the most unfavorable situation with the achievement of the above-mentioned targets in coal mining.
 The study aims to substantiate the priority directions for preserving the health of workers engaged in underground coal mining in modern production conditions based on an assessment of occupational risks to prolong their working longevity.
 Materials and methods. The authors have carried out the analysis of official statistics data (state reports of Rospotrebnadzor and the annual report of Rosstat) for 2021–2022 on the state of working conditions and occupational morbidity in the coal industry. We have summarized the materials of Rosugleprof for 2006–2022 on occupational morbidity in coal industry organizations. We have presented the data of epidemiological studies in a cohort of coal miners on the example of the Rostov region.
 Results. The authors note the largest proportion of cases of occupational pathology among employees of mining enterprises — 40.3%. The most at risk are: sinkers (10.2% of all newly identified cases of occupational diseases in 2022), miners of the treatment face (6.5%), excavator drivers (4.5%). In the structure of occupational morbidity of miners, the leading place is occupied by radiculopathy — 27.0%; sensorineural hearing loss — 22.9%; vibration disease — 22.0%; respiratory diseases (occupational bronchitis, pneumoconiosis, COPD) — more than 15.5%. In a cohort of miners with an established diagnosis of occupational diseases, it was shown that the standardized relative risk (SRR) of death from diseases of the circulatory system was 1.55 times significantly higher compared with the control population.
 Mortality from malignant neoplasms in miners was 44% higher than mortality in the population (SRR=1.44). At the same time, the death rate from the subclass malignant neoplasms of the respiratory system was 2.02 (95% CI 1.85–2.20), and from malignant neoplasms of the bronchi and lungs 2.24 (95% CI 2.04–2.46). The risk of death from respiratory diseases in the cohort of miners was more than 2 times higher than the population indicator (SRR=2.18). A significantly higher frequency of deaths from this class of diseases indicates a causal relationship with dust loads. The prevalence of coronary heart disease (CHD) among coal mine workers is higher than among the unorganized population of large cities and other groups of industrial workers.
 Conclusion. Scientists have recorded the most unfavorable working conditions in underground coal mining, which is due to the technologies used and production conditions. The prevention of diseases among miners requires the creation of health groups and the improvement of medical examination methods. Development of an integrated information system for health monitoring and personalized preventive and rehabilitation measures. To solve this problem, it is necessary to study working conditions, scientifically substantiate preventive measures, harmonize special assessment of working conditions and develop criteria for severity and intensity of work, as well as improve the technology for assessing working conditions and personalized risk assessment.
 Ethics. The study did not require the conclusion of the Ethics committee.

Diagnosis and management of systemic mastocytosis in a community hematology setting.

Systemic mastocytosis (SM) is a rare and potentially severe hematologic disorder characterized by the clonal proliferation of mast cells (MCs) into various organs. The clinical manifestations of advanced SM are caused by the uncontrolled release of cytokines and vasoactive amines from MC and disease-induced organ dysfunction. Patients with SM typically present with symptoms such as flushing, pruritus, diarrhea, and headaches, but outcomes following active treatment have not been well characterized. In this study, the clinical characteristics, treatment patterns, and natural history of an SM patient cohort diagnosed and treated within a community hematology network in the United States is described. We identified 105 patients who were diagnosed and managed in one of 19 community hematology clinics up to an index date of 1 October 2022. Data collection included patient and disease characteristics, baseline biochemistry and hematology, SM diagnostic criteria being met, biomarkers tested, CD2 and/or CD25 expression in MCs as well as serum tryptase levels at presentation. Data abstraction also included supportive care drugs and anticancer therapy used, treatment response, reason for discontinuation, and overall survival by disease subtype. A total of 105 SM patients were identified who met the inclusion criteria. The specific SM subtypes were indolent (47.6%), aggressive (9.5%), SM with an associated hematological neoplasm (19.0%), MC leukemia (1.9%), and subtype not documented (21.9%). Regardless of subtype, approximately 62% of patients did not receive SM-directed active therapy. Only 26% of patients with indolent systemic mastocytosis (ISM) received treatment compared to 65.6% with advanced subtypes. Relative to ISM cohort, the relative risk of death in patients with the advanced SM subtypes was approximately 15 times greater (hazard ratio = 15.0; 95% confidence interval: 3.3 to 66.5). SM patients present with multiple underlying symptoms, within various disease subtypes that are difficult to diagnose in a timely manner. As a result, many patients do not receive active drug therapy for their disease. Therefore, greater disease awareness is required as well as new tools for earlier disease detection.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan

BackgroundThe risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. MethodsWe analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. ResultsThe cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). ConclusionsPatients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Hematopoietic cell transplantation and cellular therapies in Switzerland. Evolution over 25years. A report from the stem cell transplantation and cellular therapies working groups of the SBST 1997-2021.

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.

Fluctuating risk of acute kidney injury-related mortality for four weeks after exposure to air pollution: A multi-country time-series study in 6 countries

BackgroundRecent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution—particulate matter ≤ 2.5 μm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)—and AKI-related mortality using a multi-country dataset. MethodsThis study included 41,379 AKI-related deaths in 136 locations in six countries during 1987–2018. A novel case time-series design was applied to each air pollutant during 0–28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. ResultsThe relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0–28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. ConclusionsThis study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.

Pathogenic Profile Characteristics and Clinical Risk Factor Analysis of Patients Who Died from Sepsis Combined with Pulmonary Infection by Metagenomic Next-Generation Sequencing.

Sepsis is one of the major diseases that seriously threatens human health, and its incidence and in-hospital morbidity and mortality rates remain high. Applying metagenomic next-generation sequencing (mNGS) technology to analyze the differences in pathogenic profiles and clinical factors in patients surviving and dying from sepsis combined with pulmonary infections provides diagnostic value and application for clinical purposes. Sixty-three BALF samples from patients with sepsis combined with pulmonary infection from Fuqing Hospital Affiliated to Fujian Medical University were collected, and all of them were tested by simultaneous mNGS and conventional microbial combined test (CMT) to compare the pathogenic profiles and clinical indices of patients who survived and died of sepsis combined with pulmonary infection and to further compare the diagnostic differences between mNGS and CMT in patients who survived and died of sepsis combined with pulmonary infection. We analyzed the diagnostic value of mNGS for sepsis combined with pulmonary infection. A total of 141 strains of pathogens were isolated from 63 samples of patients with sepsis combined with pneumonia at suspected infection sites, Klebsiella pneumoniae, Acinetobacter baumannii, and Stenotrophomonas maltophilia are predominant, and higher ApacheII, LAC, P and PT are all risk factors affecting the death of septic patients. Applying the mNGS method to patients with sepsis combined with pneumonia can improve the positive detection rate of pathogenic microorganisms and focus on death-related risk factors such as pathogenic bacteria species as well as clinical laboratory indices, which can guide clinicians to take appropriate measures to treat patients with sepsis and reduce the occurrence of death.

Lung cancer mortality trends among women across Spain: the role of birth cohorts in diverging regional patterns

Smoking among Spanish women has increased during the last 50 years and is considered by some authors a modern epidemic. However, mortality risk by cohorts may differ at a regional level, given that health inequalities (and the determinants of smoking and its consequences) are regionally patterned. We applied an Age-Period-Cohort model to identify birth cohort effects on female lung cancer mortality in Spain. We found a strong linear increase in lung cancer mortality during the 1980–2019 period in all regions. Cohorts born between 1935 and 1955 presented a higher relative risk of death at a national and subnational level. However, we found diverging cohort patterns across regions afterward, with some regions presenting a slight mortality improvement (or stagnation) in their youngest cohorts, while in other regions mortality kept increasing. This suggests that inequalities in lung cancer mortality in Spain among women are not only generationally based, but that generational risks also vary across space. Some of the regions that presented improvements in mortality among its younger cohorts are Madrid, Navarra, and the Basque Country, which are some of the wealthiest in the Country. While speculative, this could imply that improvements at a regional level might be associated with factors related to structural conditions that result in the adoption of healthy behaviors.

Quantum-First (Q-F): Clinical Bridging Study for FMS-like Tyrosine Kinase 3-Internal Tandem Duplication ( FLT3-ITD) Companion Diagnostic Development

Background Q-F (NCT02668653) showed that the highly potent, selective, type 2 FLT3 inhibitor quizartinib (Q) + standard chemotherapy ± transplantation, followed by Q monotherapy for ≥36 cycles, reduced the relative risk of death by 22.4% vs placebo (P) in newly diagnosed (nd) FLT3-ITD+ AML, with HR of 0.776 and P value of 0.0324 (PMID: 37116523). In Q-F, FLT3-ITD mutation status was determined using a FLT3-ITD mutation detection clinical trial assay (CTA) validated under design control by Navigate BioPharma Services, Inc. We describe the results of the bridging study, aimed to show agreement between the CTA & the LeukoStrat CDx FLT3 Mutation Assay (CDx, by Invivoscribe) in FLT3-ITD+ pt selection and to determine if Q efficacy (overall survival [OS]) was maintained in nd FLT3-ITD+ AML pts from Q-F, if pts had been selected using the CDx. Methods In both CTA & CDx, DNA, extracted from bone marrow (n=884 each) or peripheral blood (n=139 each), was amplified via PCR and amplicons were detected via capillary electrophoresis. A sample was considered CTA+ if the variant allele frequency ( FLT3-ITD/total FLT3) was ≥3% and CDx+ if the signal ratio (SR; FLT3-ITD/ FLT3 WT) was ≥0.05. The agreement between CTA & CDx was based on evaluating CTA+ & CTA− samples with the CDx assay. A primary analysis included the CDx detected (CDx+ & CDx−) and the CDx invalid results. A secondary analysis used CDx+ and CDx− results only. To establish agreement between CDx & CTA, positive % agreement (PPA) and negative % agreement (NPA) were determined using CTA results as reference for the agreement analysis set (AAS). Concordance was established if the lower bounds of the 95% CIs for both PPA & NPA exceeded 90% for the analysis that included the invalid CDx results. Median OS in the subgroups was calculated based on Kaplan-Meier estimates. Stratified Cox proportional hazards regression model was used to estimate HRs, 95% CI, and P value. Results Full analysis set (N=3468) included all Q-F screened CTA+ pts (n=863), all screened CTA− pts (n=2556), and pts with unknown CTA status not eligible for randomization due to other criteria (n=49). Of these, 1032 pts formed the primary analysis set (PAS), including all pts randomized in Q-F with samples available for CDx testing (N=513: Q, n=254; P, n=259) and a randomly selected subset of CTA− pts (n=519). The ascertainment rate was 95.2% (513/539), as 26 of the 539 pts randomized in Q-F were excluded from the bridging study. Within the PAS, 3 samples were not tested by CDx due to insufficient volume/DNA amount. The AAS (N=1029: CTA+, n=513; CTA−, n=516) included pts in the PAS with valid CTA results and tested with CDx. In the AAS, 6 samples (3 CTA+, 3 CTA−) did not yield valid CDx results, resulting in 1023 CDx-evaluable total pts (CTA+, n=510; CTA−, n=513). Among 510 CTA+ samples, 483 were CDx+. Among 513 CTA− samples, 513 were CDx−. Therefore, 996 samples yielded concordant results, 27 samples yielded discordant results, and 6 samples did not yield a valid CDx result for comparison. Point estimates of PPA & NPA were 94.2% & 99.4%, respectively, with invalid CDx results included in the calculation, and 94.7% & 100%, respectively, without invalid CDx results. The lower bounds of the 95% CIs were all above the corresponding acceptance criterion of 90% for PPA & NPA (Table 1). In Q-F, the prevalence of CTA+ was 24.9% among screened pts (863/3468), whereas in the bridging study, 49.9% (510/1023) of pts were CTA+: this enrichment in CTA+ pts could lead to a biased estimate of the agreement between CDx & CTA when using CDx as reference. The positive predictive value (PPV) and negative predictive value (NPV) of the CDx adjusted for this enrichment ± invalid CDx results, showed that the lower bounds of the 95% CIs were all >95% (Table 1). The efficacy OS analysis in the intent-to-treat (ITT) CDx+ population (ITT CDx+=CTA+ & CDx+; N=483: Q, n=242; P, n=241) demonstrated a clinically relevant OS improvement with Q (median OS of 29.4 months) vs P (median OS of 14.8 months), resulting in 14.6 months prolongation of median OS, with an HR of 0.794 (95% CI 0.621-1.014), corresponding to a 20.6% reduction in relative risk of death (Figure 1). Conclusions This study showed 1) agreement between CDx & CTA in identifying nd FLT3-ITD+ AML pts and 2) that OS benefit provided by Q in the ITT CDx+ population is comparable with the OS benefit in the ITT population of Q-F. The LeukoStrat CDx FLT3 Mutation Assay aids in assessing AML pts for Q therapy.

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.

Impact of Deployment on Survival in Military Personnel with Non-Hodgkin Lymphoma

Introduction: It is estimated that approximately 3.5 million active duty service members (ADSM) have deployed to Afghanistan and Iraq from 2001-2022. There has been concern about potential exposure to carcinogenic or environmental hazards during overseas deployment. A recent study found ADSM with no prior deployments had an increased risk of cancer mortality compared to those who had served in Operation Iraqi Freedom/Operation Enduring Freedom. Moreover, Nordic personnel with military deployments were also found to have a lower risk of cancer related death when compared to the general population. While there may be a link between potential environmental exposures, there is a lack of data on non-Hodgkin lymphoma (NHL) survival in servicemembers who have previously deployed. Additionally, there are no studies comparing risk of aggressive B-cell lymphoma in these patient populations. Methods: Documented cases of NHL in the DoD's Tumor Registry (Oncolog) from 2001-2022 were obtained. This information was compared to the Defense Manpower Data Center's deployment data and the two datasets were merged. ADSMs and retirees were included; dependents were excluded. A multivariable logistic regression analysis was done to assess the impact of prior deployment on cancer survival in NHL, accounting for age, race, cancer stage, ethnicity, and gender. Results: There were 2,295 servicemembers and retirees diagnosed with NHL from 2001-2022. About 20% had previously deployed (n=467). Median age at diagnosis in those who had deployed was 35 years compared to 54 years for non-deployed (p<0.001). Race, ethnicity, and gender were similar between both arms. Multivariable logistic regression analysis demonstrated prior deployment was associated with better survival after accounting for age, race, stage, ethnicity, and gender (OR 0.63, 95% CI 0.40-0.97, p=0.037). In addition to deployment status, other variables that influenced survival were age (OR 1.04, 95% CI 1.03-1.54, p<0.001), stage (OR 2.92 for stage IV vs. stage I, 95% CI 2.06-4.15, p<0.001), and race (OR 1.97 for black vs. white race, 95% CI 1.37-2.83, p<0.001). To assess whether NHL subtype played a role in these findings, a post-hoc analysis was performed on patients with B-cell NHLs, revealing that ADSM with prior deployment were equally likely to have indolent and aggressive subtypes of B-cell NHL as ADSM who had never deployed. Among personnel with prior deployment, 29.6% and 70.4% had indolent and aggressive B-cell NHLs respectively, compared to 32.9% and 67.1% amongst those who never deployed (p=0.25). Conclusions: Military personnel with NHL who had previously deployed lived longer than those with no prior deployment, even after adjusting for age differences between the two cohorts. These findings are not attributable to B-cell NHL subtype (i.e. deployed personnel did not have more indolent NHLs than non-deployed personnel). These results highlight the healthy deployer effect, in which ADSM who are deployable are required to meet minimum fitness standards, undergo a physical health assessment, and do not have disqualifying comorbidities. This study did not evaluate whether an overseas deployment is associated with an increased risk of NHL, but it does appear to provide evidence that potential deployment-related exposures do not appear to alter the biology or subtype of B-cell NHLs. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.

The FLIPI24 Prognostic Model Identifies Poor Outcomes in Non-Immunochemotherapy Treated Patients with Follicular Lymphoma

Background: We previously reported thatearly events in follicular lymphoma (FL), defined as progression of disease within 24 months (POD24) or early transformation to a more aggressive histology, are significantly associated with increased risk of lymphoma related death. To refine clinical management, the FLIPI24 prognostic model was developed to predict the risk of early events after starting immunochemotherapy (IC) (Maurer et al, 2022). The FLIPI24 model was found to be significantly superior to standard clinical models for prediction of both event-free survival at 24 months (EFS24) and overall survival (OS) in internal and external validation sets of patients receiving IC. We sought to evaluate the prognostic ability of the FLIPI24 model in patients with FL not receiving IC. Methods: The cohort consists of prospectively enrolled patients in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and the multicenter Lymphoma Epidemiology of Outcomes (LEO) Cohorts. Data were collected from medical records by standard protocol with all events verified by medical record review. Eligible patients were those diagnosed with grades 1-3A FL and initiated observation, rituximab monotherapy, radiation, or other non-IC therapy. The FLIPI24 model utilizes 5 continuous variables: age (linear 60-90 years with inflection at age 75), HGB (linear 8-17 g/dL), WBC (linear 4-11x10 9/L), LDH/ULN (linear 0.5-5), and B2M (linear 1-10 mg/L). FLIPI24 risk is grouped as follows: low risk (≤10%], low-average risk (10-15%], average risk (15-20%], high risk (20-40%], very high risk (>40%) for an early event. EFS was defined as time from diagnosis to progression, relapse, (re)treatment, histologic transformation, or death due to any cause. OS was defined as the time from diagnosis until death from any cause. Cox models and Kaplan Meier curves were used to evaluate association between FLIPI24 and EFS or OS. Results: 1542 patients initiating non-IC management approaches at diagnosis from 2002-2020 were identified. 51% were >60 years (IQR 52-70), and 49% were male. Most patients (86%) had FL grade 1-2. 61% of patients met any criteria for high tumor burden per GELF, BLNI, or GITMO based on available variables. Treatment approaches were 833 observation (54%), 315 rituximab monotherapy (20%), 186 radiation (12%), and 208 other non-IC approaches (14%). At median follow-up of 58 months, EFS24 was 73.8% (95% CI: 71.6%, 76.1%), 5-year OS was 90.9% (95% CI: 89.3%, 92.5%) and 253 (16%) patients died. The FLIPI24 score identified poor outcomes among patients with high/very high-risk score (FLIPI24 >20%), with median EFS of 1.8 years (95% CI, 1.3, 3.28) and 5 year OS of 65.1% (95% CI: 55.9-75.8) (Figure 1). When evaluating patient subsets, for patients with high tumor burden (defined based on available variables) and high/very high-risk score, median EFS was 1.6 years and 5 year OS was 64.6% (95% CI: 54.9%-76.1%). Among patients with low tumor burden FL and high/very high-risk score, median EFS was 2.0 years (95% CI: 0.84-NA) and 5 year OS was 66.2% (95% CI: 42.4%-100%). Patients undergoing observation with high/very high-risk score similarly had shortened median EFS of 1.53 years (95% CI: 1.25-NA) and 5 year OS of 68.9% (95% CI: 56.4%-84.1%). The FLIPI24 had superior concordance for OS (c=0.726) compared to the FLIPI (c=0.646) when evaluated in patients not treated with IC. Results were comparable in the subsets of patients observed (c=0.706 vs 0.596) and receiving rituximab monotherapy (c=0.764 vs 0.721). Conclusion: The FLIPI24 model has been previously validated to provide an individual risk score at diagnosis for the likelihood of experiencing an event within 24 months from starting IC. Here we demonstrate that a high FLIPI24 score predicts for poorer outcomes following non-IC strategies including observation, treatment with radiation, and rituximab monotherapy. The FLIPI24 has better prognostic performance for OS than FLIPI in this non-IC population. High FLIPI24 in patients not treated with IC identifies a patient population who should be considered for IC and/or novel frontline therapies when feasible.

Absolute and Relative Risks of Hematologic Disease and Cause-Specific Death in Individuals with Incidentally Discovered Thrombocytopenia: A Prospective Study of Two Independent General Population Cohorts Including 486,782 Individuals from the United Kingdom and Denmark

Background: Incidentally discovered thrombocytopenia in asymptomatic individuals often result in a referral to hematology. Clinical decisions for these individuals are mostly based on local practice, as little evidence exists on their risk of hematologic disease and death. We aim to lay ground for an evidence-based clinical approach to incidental thrombocytopenia with or without concurrent anemia by studying relative and absolute risk of being diagnosed with hematologic disease, death from hematologic disease and death from any cause. Methods: We studied 382,424 general population individuals from the United Kingdom (UK) Biobank aged 40-70 years, of whom 9,151 had thrombocytopenia with or without anemia. Individuals with leukocytosis, neutropenia or prior hematologic disease were excluded. As a validation cohort, we studied 104,358 Danish general population individuals. All individuals attended a health examination and had platelets, hemoglobin, leukocyte and differential count measured at study enrolment. Individuals were followed prospectively for up to 16 years for hematologic disease and cause-specific death using national registries, covering all deaths and almost all cancer cases in the UK and Denmark. Results: Among 382,424 individuals from the UK, 6,044 had hematologic disease during follow-up, 28,403 died from any cause and 1,213 died due to hematologic disease. For all analyses, the reference group was individuals with normal platelet count and normal hemoglobin. Individuals with isolated mild thrombocytopenia (platelets 100-149 x 10 9/L) or isolated moderate-severe thrombocytopenia (<100 x 10 9/L) had increased relative risk of hematologic disease (multivariable adjusted Cox regression hazard ratios [HR] 2.19; 95% CI:1.94-2.47 and HR 7.68; 6.35-9.29, respectively), death from hematologic disease (HR 1.81; 1.37-2.38 and HR 2.80; 1.45-5.39, respectively) and death from any cause (HR 1.30; 1.22-1.39 and HR 1.84; 1.58-2.16, respectively). Individuals with mild thrombocytopenia combined with mild anemia (hemoglobin 11-11.8 g/dL for women; 11.9-13.4 for men) also had increased risk of hematologic disease (HR 5.36; 3.82-7.52), death from hematologic disease (4.99; 2.49-10.04), and death from any cause (2.57; 2.14-3.10). Relative risk estimates were increased to a similar or higher extent in individuals having moderate-severe thrombocytopenia with mild anemia, mild thrombocytopenia with severe anemia (hemoglobin <11 g/dL for women; <11.9 for men) or moderate-severe thrombocytopenia with severe anemia. When studying absolute risk (Figure 1), the 10-year risk of death from any cause was especially high (23-53%) in individuals aged 60-70 years with combined thrombocytopenia and anemia. However, 10-year risk of death from hematologic disease was below 5% for all combinations of sex, age, platelet count and hemoglobin, except for women (5.0%) and men (7.9%) aged 60-70 years having moderate-severe thrombocytopenia with mild anemia. For risk of hematologic disease, absolute 10-year risk was below 5% for all age and sex-groups with isolated mild thrombocytopenia, while 10-year risk was as high as 21% in 60-70 year-old men having mild anemia combined with moderate-severe thrombocytopenia. For individuals with thrombocytopenia with or without anemia, the most common hematologic diseases were lymphoid malignancies (41% of diagnoses; HR 1.73; 1.49-2.01), ITP (34%; HR 22.85; 18.56-28.13), and myeloid malignancies (25%; HR 2.90; 2.39-3.52). Among causes of death in individuals with thrombocytopenia were non-hematologic cancer (35% of deaths; HR 1.21; 1.10-1.33), heart disease (21%; HR 1.43; 1.27-1.62), infections (4%; HR 1.84; 1.36-2.49), and bleeding (2%; HR 1.37; 0.94-1.99). In the independent Danish validation cohort, results were generally similar to those presented in Figure 1. Conclusion: Individuals with thrombocytopenia with or without anemia had increased relative risk of hematologic disease, death from hematologic disease and death from any cause. However, 10-year absolute risk of death from hematologic disease was below 5% for most combinations of sex, age, platelet count and hemoglobin. Our absolute 10-year risk estimates can help clinicians to identify low and high-risk individuals and guide decisions on which individuals with incidentally discovered thrombocytopenia that should undergo investigations for possible hematologic disease.

Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17

ObjectiveTo determine the relative risk of death following exposure to treatments for OUD compared to no treatment. MethodsIn this retrospective cohort study we compiled and merged state agency data on accidental and undetermined opioid overdose deaths in 2017 and exposures to OUD treatment in the prior six months to determine incidence rates following exposure to different treatment modalities. These rates were compared to the estimated incidence among those exposed to no treatment to determine relative risk of death for each treatment exposure. ResultsIncidence rates for opioid poisoning deaths for those exposed to treatment ranged from 6.06±1.40 per 1000 persons exposed to methadone to 17.36±3.22 per 1000 persons exposed to any non-medication treatment. The estimated incidence rate for those not exposed to treatment was 9.80±0.72 per 1000 persons. With no exposure to treatment as referent, exposure to methadone or buprenorphine reduced the relative risk by 38% or 34%, respectively; the relative risk of non-medication treatments was equal to or worse than no exposure to treatment (RR = 1.27–1.77). Principal conclusionsExposure to non-MOUD treatments provided no protection against fatal opioid poisoning whereas the relative risk was reduced following exposures to MOUD treatment, even if treatment was not continued. Population level efforts to reduce opioid overdose deaths need to focus on expanding access to agonist-based MOUD treatments and are unlikely to succeed if access to non-MOUD treatments is made more available.

Income and Education Affect Prognosis and Treatment in Symptomatic Myeloma: A Population-Based Study on 8672 Multiple Myeloma Patients Diagnosed 2008-2021 from the Swedish Myeloma Registry

Introduction While survival in myeloma has improved with new treatment modalities, a substantial variation in mortality remains. This variation cannot entirely be explained by differences in known prognostic factors, such as age and genetic risk group. A link between socioeconomic factors and prognosis has gained attention during recent years, but most studies derive from populations with unequal access to health care. We tested whether income and education affects myeloma treatment and survival also in a country where nearly all health care is publicly funded. Materials and methods Study population The study base included all Swedish patients with symptomatic myeloma diagnosed between 2008 and 2021 (n=8672) and included in the Swedish Myeloma Registry. Data on stem cell transplants (HSCT) were retrieved from the 1-year follow-up form in the myeloma register. Data on lenalidomide, pomalidomide, and melphalan treatment were retrieved from the Swedish Prescribed Drug Register. Data on comorbidities were retrieved from the Swedish Patient Register and the Swedish Cancer Register and Charlson comorbidity index was constructed based on diagnoses registered within five years preceding myeloma diagnosis. Data on socioeconomic conditions were retrieved from the Integrated Database for Labor Market Research (LISA), held by Statistics Sweden. Education level was divided into three categories; primary school only (≤9 years), some college or university (≥13 years), or anything between these two (10-12 years). To avoid undue effect of outliers, personal and family income were grouped into highest quartile, lowest quartile and those in-between. Patients were followed in Swedish population statistics until death, permanent emigration or 31 st December 2022. Statistical analysis Analyses on overall survival were performed with Kaplan-Meier plots and with Cox proportional hazards models, yielding hazard ratios (HR) with 95% confidence intervals (95% CI) as measures of relative risk of death. Differences in treatment were assessed by Poisson regression. All p-values were two-sided and a value below 0.05 was considered statistically significant. All analyses were performed with SAS 9.4 statistical software (SAS Inc., Cary, NC). Ethical considerations The study has been approved by the Swedish Ethical Review Authority (2020-01729). All data were anonymized before analyses. Results Median survival was doubled in patients with higher education, compared with patients with primary school only (6.0 years vs 3.0 years). Similarly, patients in the highest family income quartile had a median survival of 7.5 years, compared to 2.8 years among patients from the lowest quartile (Figure 1). The survival differences were to some degree explained by differences at baseline, in particular age at diagnosis. In a multivariable proportional hazards regression, with adjustments for age group, sex, year of diagnosis and comorbidity index, low income patients had 40% higher risk of death than high income patients (HR 1.6, 95% CI 1.5-1.8) and patients with primary school only had 30% higher risk of death compared to patients with higher education (HR=1.4, 95% CI=1.3-1.5), p<0.0001 for both analyses. Patients with the highest family incomes were also more likely to have been treated with a stem cell transplant, a lenalidomide containing regimen, or a pomalidomide containing regimen, while patients with the lowest family incomes were more often treated with melphalan-prednisone based regimens (Table 1). Discussion Education and private economy are correlated with survival in myeloma, even in a country where the cost of health care is covered almost completely by taxes. The differences are not explained by age and comorbidities alone. Our data also suggest that doctors' choices of myeloma treatment are influenced by socioeconomic factors. The data indicate that myeloma survival could increase with more than a year if we could achieve the same results for all patients as we do with the wealthiest and most educated quartile.

Kinetics of Complete Remission (CR) and CR Duration and Its Impact on Overall Survival (OS) and Event-Free Survival (EFS) in Quantum-First

Background Results from the phase 3 QuANTUM-First study (NCT02668653) showed that in patients (pts) with newly diagnosed (nd) acute myeloid leukemia (AML) and positive for FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3-ITD+), the addition of the oral, highly potent, and selective, type 2 FLT3 inhibitor quizartinib (Quiz) to standard chemotherapy ± allogeneic hematopoietic cell transplantation (allo-HCT), followed by continuation monotherapy for up to 3 years, decreased the relative risk of death by 22.4% vs placebo (PBO) (PMID: 37116523). We assessed 1) the impact of CR duration on OS and EFS and 2) the kinetics of CR achievement over time after induction. Methods QuANTUM-First enrolled pts aged 18-75 years with FLT3-ITD+ nd AML, randomized to receive standard induction chemotherapy with either Quiz (40 mg/d) or PBO, and stratified by region (Europe, North America, or Asia/Australia/South America), age (<60 years, ≥60 years), and white blood cell count (WBC; <40×10 9/L, ≥40×10 9/L) at diagnosis. Pts who achieved CR or CR with incomplete hematologic recovery (CRi) received up to 4 cycles of high-dose cytarabine combined with Quiz (40 mg/d) or PBO and/or allo-HCT followed by up to 3 years (36 cycles) of continuation therapy with Quiz (30-60 mg/d) or PBO. OS was the primary endpoint, EFS and rates of CR and composite complete remission (CRc) were secondary endpoints; CR duration was an exploratory endpoint. The impact of CR duration on OS was analyzed by extended Cox regression model stratified by region, age, and WBC count at diagnosis and included treatment group and CR duration status (time-dependent covariate). CR duration status was 0 for pts who did not achieve CR, 1 for CR pts throughout the duration of sustained CR, and 0 for CR pts after they relapsed. Results Of the 539 randomized pts enrolled in QuANTUM-First (Quiz, n=268; PBO, n=271), there were 297 CR pts (Quiz, n=147; PBO, n=150) based on independent review committee assessment after 1 to 2 courses of induction. Among 533 treated pts, 20% had 2 induction cycles. Baseline characteristics in CR pts were well balanced between arms: median age in years (range), 56.0 (23-75) vs 55.5 (20-74); females, 55.8% vs 60.0%; ECOG ≥1, 64.6% vs 63.3%; mutated NPM1 / CEBPA,66.7% vs 64.7% / 25.9% vs 23.3%; variant allele frequency (VAF) >25%, 68.7% vs 66.7%; and WBC count at diagnosis ≥40×10 9/L, 55.8% vs 49.3%. Median OS in CR pts was not reached (95% CI 48.6 months-NE) in the Quiz arm vs 35.4 (95% CI 15.1-NE) months in the PBO arm (HR 0.572, 95% CI 0.400-0.816; Figure 1). Although CR rates were similar between arms (55% in both), median CR duration was longer with Quiz vs PBO (38.6 months, 95% CI 21.9-NE vs 12.4 months, 95% CI 8.8-22.7; HR 0.621, 95% CI 0.451-0.857). Based on the extended Cox model, CR duration status covariate was strongly predictive for OS (HR 0.156, 95% CI 0.113-0.216; nominal P<0.0001; Figure 2). Importantly, the HR for Quiz vs PBO effect on OS in the model with the time-dependent covariate CR duration status was higher (HR 0.851, 95% CI 0.672-1.076) vs the HR of the primary OS analysis (HR 0.776, 95% CI 0.615-0.979), implying that a substantial fraction of OS benefit was mediated through its effects on achieving a durable CR (Figure 2). EFS favored Quiz over PBO when induction treatment failure (ITF) was defined as not achieving CRc or CR, by the end of induction up to day 56 from the last induction cycle, with HR 0.729 (95% CI 0.592-0.897; nominal P=0.0031) and 0.818 (95% CI 0.669-0.999; nominal P=0.032), respectively. EFS was similar between arms when ITF was defined, according to FDA guidance, as not achieving CR by day 42 from the start of the last induction cycle (HR 0.916, 95% CI 0.754-1.114; P=0.24; primary EFS analysis). Between day 42 and the end of the induction phase, there were 51 pts who achieved CR (Quiz, n=33; PBO, n=18), and they were considered as ITF with EFS event on day 1 in the primary analysis of EFS. Among these 51 pts, 9 (Quiz, n=5; PBO, n=4) had CRi by day 42 and became CR after day 42 in the induction phase. Conclusions These analyses demonstrated that in QuANTUM-First: 1) a substantial fraction of the estimated effect of Quiz on OS was mediated through its effect on achieving a durable CR and 2) more pts in the Quiz arm vs the PBO arm achieved CR after day 42 of the last induction cycle, suggesting that there was a delay in CR achievement with Quiz. Longer EFS was observed in Quiz over PBO based on the EFS definition including CRs between day 42 and end of induction.

Quantum-First: Safety By Treatment Phase and By Age in Newly Diagnosed (nd) Patients (pts) with FMS-like Tyrosine Kinase 3-Internal Tandem Duplication ( FLT3-ITD) Positive Acute Myeloid Leukemia (AML)

Background Results from the phase 3 QuANTUM-First study (NCT02668653) showed that in nd FLT3-ITD+ AML pts, the addition of the oral, highly potent, selective, type 2 FLT3 inhibitor quizartinib (Quiz) to standard chemotherapy ± allogeneic hematopoietic cell transplantation (allo-HCT), followed by Quiz monotherapy for up to 36 cycles (3 years [yrs]), decreased the relative risk of death by 22.4% vs placebo (PBO), with a generally manageable safety profile (PMID: 37116523). We describe safety by treatment phase (Induction [IND], Consolidation [CONS], Continuation [CONT]) and by age group (<60, 60-64, ≥65 yrs). Methods Eligible pts (18-75 yrs) with nd FLT3-ITD+ AML were randomized 1:1 to Quiz (40 mg/d) or PBO + standard IND chemotherapy. Pts in complete remission (CR) or CR with incomplete neutrophil or platelet recovery received standard CONS chemotherapy + Quiz (40 mg/d) or PBO and/or allo-HCT (Quiz/PBO not given with allo-HCT), followed by CONT of single-agent Quiz (30-60 mg/d) or PBO for up to 36 cycles. Safety was evaluated in pts treated with ≥1 dose of Quiz or PBO. Treatment-emergent adverse events (TEAEs) were coded by MedDRA v24.0, severity by NCI-CTCAE v4.03. Results In both arms, median treatment durations were 2 weeks in IND, 4 weeks in CONS, and 1.3 yrs in CONT. Rates of TEAEs and grade ≥3 TEAEs were similar in both arms in IND & CONS, although grade ≥3 TEAEs were more common with Quiz vs PBO in CONT (Table 1). In IND & CONS, the most common TEAEs were gastrointestinal (GI) AEs (diarrhea, nausea, vomiting), infections (pneumonia, sepsis), hypokalemia, pyrexia, febrile neutropenia, and rash. In IND & CONS, myelosuppression occurred in most pts in the Quiz and PBO arms, with a median blood count recovery time <4 weeks from the time of onset. In CONT, most common TEAEs were upper respiratory tract infections, GI AEs, cytopenias, and ALT increase. In CONT, more pts with Quiz had myelosuppression, with trends toward earlier onset and delayed recovery with Quiz. ECG QT prolonged was more common with Quiz vs PBO in all phases, QTcF >500 ms was low (2.3%) and observed in IND & CONS only. Ventricular arrythmias were few with Quiz (2 pts [0.8%] had cardiac arrest/ventricular fibrillation with severe hypokalemia). Infections were the most common serious TEAEs (TESAEs), with febrile neutropenia, pneumonia, and sepsis in IND & CONS and pneumonia and viral infections in CONT. TEAEs leading to death were numerically higher with Quiz vs PBO in IND & CONS, mainly due to infections in older pts, but numerically lower with Quiz vs PBO in CONT. In IND & CONS, TEAEs leading to dose interruptions or dose reductions were similar in both arms, whereas TEAEs leading to discontinuation (disc) were higher with Quiz vs PBO. TEAEs leading to dose interruptions, dose reductions, or disc in CONT were higher with Quiz vs PBO. TEAE leading to disc of Quiz were mostly infections in IND & CONS and cytopenias in CONT. Cytopenias and QT prolonged were the most common AEs leading to dose modifications and were more common with Quiz. There was no evidence of increasing toxicity with long-term Quiz therapy for up to 36 cycles in CONT, and no new AEs were observed in pts receiving >12 cycles. Rates of TEAEs and grade ≥3 TEAEs were similar in both arms across age groups (Table 2). TESAEs, TEAEs leading to death, and TEAEs leading to disc were more common in older pts (≥65 yrs [n=134]) vs younger pts (<60 and 60-64 yrs [n=399]) in both arms. Infections in the elderly were most commonly severe, serious, and fatal AEs and a main cause of more early deaths (<60 days of Quiz start). TEAEs leading to dose modifications were higher with Quiz vs PBO across age groups. In the Quiz arm, cytopenias, headache, rash, cough, ALT increase, hypomagnesemia, oropharyngeal pain, and back pain were more common in younger vs older pts; ECG QT prolonged was highest in the 60-64 yrs group. GI AEs and were more common in older pts with Quiz. QTcF >500 ms occurred mainly in pts 60-64 yrs with Quiz. Conclusions In QuANTUM-First, infections and cytopenias associated with Quiz were observed across phases. Fatal infections were more common with Quiz in IND & CONS but not in CONT. Rates of prolonged QTcF >500 ms were low overall, occurring mostly in IND & CONS, not in CONT. Pts ≥65 yrs had higher TESAEs, TEAEs leading to death (including early death), and TEAEs leading to disc (mainly infections) vs younger pts in both arms. Quiz safety profile in different treatment phases and age subgroups supports an overall positive benefit/risk.

Asthma and COPD as co-morbidities in patients hospitalised with Covid-19 disease: a global systematic review and meta-analysis

BackgroundFactors predisposing to increased mortality with COVID-19 infection have been identified as male sex, hypertension, obesity, and increasing age. Early studies looking at airway diseases gave some contradictory results. The purpose of our study was to determine global variation in studies in patients hospitalized with COVID-19 in the prevalence of COPD and asthma; and to determine whether the presence of asthma or COPD affected mortality in the same hospital population.MethodsA systematic review and meta-analysis of the published literature of COPD and asthma as co-morbidities in patients hospitalized with COVID-19 was performed, looking firstly at the prevalence of these diseases in patients hospitalized with COVID-19, and secondly at the relative risk of death from any cause for patients with asthma or COPD.ResultsPrevalence of both airway diseases varied markedly by region, making meaningful pooled global estimates of prevalence invalid and not of clinical utility. For individual studies, the interquartile range for asthma prevalence was 4.21 to 12.39%, and for COPD, 3.82 to 11.85%. The relative risk of death with COPD for patients hospitalized with COVID-19 was 1.863 (95% CI 1.640–2.115), while the risk with asthma was 0.918 (95% CI 0.767 to 1.098) with no evidence of increased mortality.ConclusionsFor asthma and COPD, prevalence in patients hospitalized with COVID-19 varies markedly by region. We found no evidence that asthma predisposed to increased mortality in COVID-19 disease. For COPD, there was clear evidence of an association with increased mortality.Trial registrationThe trial was registered with PROSPERO: registration number CRD42021289886.

Colon cancer survival after radical surgery performed in hospitals of the Arkhangelsk region: a population-based analysis

Background. surgery is the main method of treatment of colon cancer (cc). Radical surgery performed in non-specialized hospitals can lead to the adverse outcomes.The aim of this study was to assess CC survival after radical surgery performed in state hospitals of the arkhangelsk region (North-West Russia) in 2010–21.Material and Methods. data on all the 2142 cases of radical surgery of CC were obtained from the arkhangelsk regional cancer registry (ARCR). One- and five-year cancer-specific survival rates were estimated by the survival tables; cumulative survival function was calculated by the Kaplan–meier method. Univariate and multiple cox regression analysis was carried out to identify independent predictors associated with CC death risk after radical surgery in state hospitals (incl. sex, age at the time of diagnosis, topography, morphology and stage of CC).Results. less than half (42.8 %) of patients underwent surgery at the arkhangelsk clinical cancer center (accc), a single specialized hospital. one- and five-year survival rates of all patients were 86.5 % (95 % CI: 84.9–87.9 %) and 65.1 % (95 % ci: 62.7–67.4 %), respectively. The 5-year survival rate of patients who underwent surgery in the accc was significantly higher than that in patients who underwent surgery in other state non-specialized hospitals (76.0 % (95 % ci: 72.5–79.0 % versus 49.3–73.8 %, p<0.0001). The relative risk of death of CC patients depended on the state hospital where radical surgery was performed and the stage of CC; it did not depend on patients’ sex, morphology and topography of CC.Conclusion. our results demonstrate the need to search for specific reasons for the relatively low survival in patients after radical surgery performed in non-specialized hospitals.

High-sensitivity troponin-T concentrations and long-term risk of death in patients with acute pulmonary embolism

Abstract Background Cardiac troponin elevation is associated with adverse short-term prognosis in patients with pulmonary embolism (PE). However, it is unknown whether high-sensitivity troponin concentrations predict long-term outcomes and whether serial measurements offer additional prognostic information in this setting. Purpose To determine short- and long-term prognostic implications of high-sensitivity troponin-T (hsTnT) concentrations and their changes from baseline, in patients with acute PE. Methods Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with a PE from 2013 through 2019 and merged them with all records of at least one hsTnT (99th percentile upper reference limit, 13.5 ng/l) measurement obtained during the same hospitalization. Absolute and relative risks for death from any cause at days 0-30 and 31-365 were calculated through multivariable logistic regression with average treatment effect modeling. Moreover, we tested whether hsTnT changes (in those who had a second measurement available ≥1 hour and ≤7 hours after the first measurement) were associated with additional prognostic information. Results At least one hsTnT measurement was available in 4611 individuals. Median age (25th-75th percentile) was 70.8 (58.6-79.5) years, and 2312 (50.1%) were women. One-hundred and forty-one (3.1%) patients had a prior venous thromboembolic event, 731 (15.9%) had known coronary artery disease, and 1001 (21.7%) had a history of cancer. Median baseline hsTnT was 29 (25th-75th percentile, 14-79) ng/l, and 1082 (76.5%) had an elevated concentration. Four-hundred and thirty-one (9.3%) individuals had died at 30 days, while an additional 614 (14.7% of 30-day survivors) died between days 31-365. hsTnT concentration displayed a significant, non-linear association with death (P<0.001). Figure 1 shows the unadjusted 30-day risk of death stratified for hsTnT quartiles, while Figure 2 shows the risk at days 31-365 (with 0 on the x-axis representing day 30 from the index event). Upon multivariable adjustment (including absence or presence of acute cor pulmonale), the risk of death at both timepoints remained significantly higher among individuals in each of quartiles 3 and 4 versus quartile 1 (P<0.05), with quartile 2 showing a trend (P=0.06 and P=0.07 for short- and long-term death, respectively). In 1247 subjects with two hsTnT measurements available, absolute and relative changes from baseline did not appear to carry additional prognostic information, nor did switching from normal to elevated hsTnT or vice versa, though the latter was only observed in very few persons. Conclusions In patients with acute PE, elevated hsTnT concentrations were associated with both short- and long-term mortality, but unlike in acute coronary syndromes, the utility of drawing a second sample appeared limited.Figure 1Figure 2