Competing Risk Survival Analysis Research Articles

Longitudinal Assessment of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography.

To longitudinally investigate the changes in intraretinal microvascular abnormalities (IRMAs) over time, employing swept-source optical coherence tomography angiography in eyes with diabetic retinopathy. In this retrospective, longitudinal study, we evaluated 12 × 12-mm swept-source optical coherence tomography angiography centered on the macula at baseline and last available follow-up visit for (1) IRMA changes during follow-up, defined as (a) stable, (b) regressed, (c) obliterated, and (d) progressed; and the (2) development of new neovascularization (NV) and their origins. Competing-risk survival analysis was used to assess the factors associated with these changes. In total, 195 eyes from 131 participants with diabetic retinopathy were included. Stable, regressed, obliterated, and progressed IRMA were observed in 65.1%, 12.8%, 11.3%, and 19% of eyes with diabetic retinopathy, respectively. Anti-VEGF injections during the follow-up periods and a slower increase of foveal avascular zone were associated with IRMA regression (P < 0.001 and P = 0.039). Obliterated IRMA were correlated with previous panretinal photocoagulation (P < 0.001) and a lower deep capillary plexus vessel density at baseline (P = 0.007), as well as with follow-up anti-VEGF injections (P = 0.025). A higher baseline ischemia index (ISI) and panretinal photocoagulation during the follow-up periods were associated with IRMA progression (P = 0.049 and P < 0.001). A faster increase in ISI predicted the development of NV elsewhere (NVE) from veins (P < 0.001). No significant factors were found to be associated with NVE originating from IRMA. Changes in IRMA closely correlated with the severity of retinal ischemia and treatment. Notably, our study confirmed the potential, yet relatively rare, development of NVE from IRMA in a large cohort; however, the risk factors associated with this transformation require further exploration.

ON THE MOMENTS OF THE 3-PARAMETER GOMPERTZ DISTRIBUTION

Gompertz distribution is a classical probability distribution extensively used in actuarial science, reliability, and survival analysis. Gompertz distribution also plays a role in various fields, such as biology, economics, and marketing analysis. Some extensions of this distribution have been studied and applied to various problems. In this article, we are concerned with some statistical properties of a 3-parameter Gompertz distribution. This extension of the Gompertz distribution introduced has been used in studying competing risk survival analysis. Our main results are the derivation of moments of this distribution and other statistical properties related to moments, such as moment generating function, mean residual life function, mean inactivity time and Lorenz curve. These results will serve as a complement to the theoretical aspect of the analysis of the distribution.

#1578 Left ventricular ejection fraction: association with risk of mortality and the incidence of AVF dysfunction

Abstract Background and Aims Ejection fraction (EF) and chronic heart failure (HF) are often considered as criteria for the possibility of arteriovenous fistula (AVF) creation in relation to an increased risk of death, without sufficient evidence for this. There is, however, rare but compelling evidence that low EF increases the risk of AVF dysfunction. Aims: to evaluate the association between EF at the time of AVF creation and the incidence of adverse cardiovascular events, all-cause mortality, as well as AVF dysfunction Method This retrospective cohort study included 962 adult patients who had a first-time created functioning AVF. Only patients with a more than three months period after AVF creation and within a five-year period were included. The mean follow-up period was 34 ± 13 months. Four groups were identified based on EF and the presence of HF at the time of AVF creation (transthoracic echocardiogram): HF with reduced EF (rEF) &amp;lt;40%, with mid-range (mrEF) of 40-49%, or with preserved EF (pEF) ≥50% + HF, and a “no HF” group with EF ≥50% and no HF. Results In the univariate analysis, a reduced EF was associated with an increased risk of mortality, with the hazard ratios (HRs) of 2.706 [95% CI 1.330; 5.507], p = 0.006 for mrEF and 8.250 [95% CI 2.621; 25.97], p &amp;lt; 0.001 for rEF, compared to the “no HF” group (here and thereafter)—Fig. 1. However, after adjusting for age, sex, and Charlson Comorbidity Index (CCI), the EF was not significantly associated with the risk of death. Only the CCI score remained a significant factor (HR = 1.748 [95% CI 1.482; 2.063], p &amp;lt; 0.001). A decreased EF was associated with the incidence of AVF dysfunction both in the univariate analysis and after adjustments. In the univariate analysis, the incidence rate ratios (IRRs) of 6.88 [95% CI 3.88; 12.1], p &amp;lt; 0.001 for mrEF, and 19.9 [95% CI 8. 64; 41.6], p &amp;lt; 0.001 for rEF, were shown. After adjusting for age, sex, and CCI, the IRR for mrEF was 8.96 [95% CI 5.81; 13.7], p &amp;lt; 0.001, and for rEF it was 23.4 [95% CI 13.8; 38.6], p &amp;lt; 0.001. Even in the presence of polycystic kidney disease and diabetes mellitus in the fully adjusted model, the association between EF and the incidence of AVF dysfunction remained statistically significant: the IRR was 8.61 [95% CI 5.61; 13.1], p &amp;lt; 0.001 for mrEF, and 33.4 [95% CI 19.5; 56.2], p &amp;lt; 0.001 for rEF. The findings were confirmed in a sensitivity analysis that included adjustments for unplanned onset of dialysis and competing risks survival analysis (death—outcome of interest, conversion of HD to PD or kidney transplantation and conversion of AVF to CVC—competing events). According to our results patients with EF&amp;lt;40% will inevitably lose AVF function for various reasons within 3.5 years—Fig. 2. Meanwhile, this approach will give the patient additional time of HD via AVF, but not CVC, without increasing the risk of death, subject to Qa monitoring. Conclusion In patients with CKD 5 who are initiating treatment with maintenance hemodialysis, a decreased EF is associated to a greater extent with a higher risk of AVF dysfunction than with an increased risk of mortality. The burden of comorbidities, rather than a standalone assessment of EF, is one of the major risk factors determining patient survival.

The association between hypoalbuminemia and risk of death due to cancer and vascular disease in individuals aged 65 years and older: findings from the prospective Moli-sani cohort study

Serum albumin is inversely associated with overall mortality, but its association with specific causes of death remains uncertain. This study aims to investigate whether hypoalbuminemia, defined as serum albumin levels ≤35g/L, is associated with mortality specifically attributed to cancer and/or vascular diseases. Serum albumin levels were measured in the population-based, prospective cohort of the Moli-sani study, established between 2005 and 2010. Hypoalbuminemia was defined as serum albumin levels ≤35g/L. Cause-specific mortality was assessed using the validated Italian mortality registry and coded according to the International Classification of Diseases, Revision 9. Over a median follow-up period of 13.1 years, the relationship between serum albumin and mortality, adjusted for covariates, was investigated using competing-risk survival analysis. The analysed cohort comprised 17,930 individuals aged ≥35 years, of whom 8445 were men (47.1%). The mean age was 54 years (standard deviation (SD)=11 years), with 3299 individuals (18.4%) aged older than 65 years. All participants had C-reactive protein levels <10mg/L and no history of liver, renal, cardiovascular, or cancer disease. Hypoalbuminemia was found in 406 individuals (2.3%). The study documented a total of 1428 deaths, with 574 attributed to cancer and 464 to vascular causes. Hypoalbuminemia was independently associated with mortality when compared to serum albumin >40g/L (Hazard Ratio (HR)=1.61, 95% Confidence Interval: 1.21-2.13). A decrease of 1-SD in serum albumin levels corresponded to HR of 1.16 (1.09-1.22), 1.16 (1.05-1.28), and 1.13 (1.03-1.23) for total, vascular and cancer mortality, respectively. Upon stratifying by age, hypoalbuminemia was associated with total mortality solely in those aged ≥65 years (HR=1.83; 1.33-2.50) but not in the <65 years group (HR=1.03; 0.53-2.00; P<0.0001 for difference). Similar age-related patterns emerged for vascular death (per 1-SD decrease HR=1.19; 1.07-1.33 in individuals ≥65 years and HR=1.05; 0.86-1.29 in individuals <65 years) and cancer mortality (HR=1.15; 1.02-1.30; ≥65 years and HR=1.08; 0.96-1.23; <65 years). Individuals ≥65 years old with serum albumin levels ≤35g/L are at higher risk of total, cancer, and vascular mortality. This paper was developed within the project funded by Next Generation EU-"Age-It - Ageing well in an ageing society" project (PE0000015), National Recovery and Resilience Plan (NRRP)-PE8-Mission 4, C2, Intervention 1.3.

Atrial fibrillation: age at diagnosis, incident cardiovascular events, and mortality.

Patients with atrial fibrillation (AF) are at increased risks of cardiovascular diseases and mortality, but risks according to age at diagnosis have not been reported. This study investigated age-specific risks of outcomes among patients with AF and the background population. This nationwide population-based cohort study included patients with AF and controls without outcomes by the application of exposure density matching on the basis of sex, year of birth, and index date. The absolute risks and hazard rates were stratified by age groups and assessed using competing risk survival analyses and Cox regression models, respectively. The expected differences in residual life years among participants were estimated. The study included 216 579 AF patients from year 2000 to 2020 and 866 316 controls. The mean follow-up time was 7.9 years. Comparing AF patients with matched controls, the hazard ratios among individuals ≤50 years was 8.90 [95% confidence interval (CI), 7.17-11.0] for cardiomyopathy, 8.64 (95% CI, 7.74-9.64) for heart failure, 2.18 (95% CI, 1.89-2.52) for ischaemic stroke, and 2.74 (95% CI, 2.53-2.96) for mortality. The expected average loss of life years among individuals ≤50 years was 9.2 years (95% CI, 9.0-9.3) years. The estimates decreased with older age. The findings show that earlier diagnosis of AF is associated with a higher hazard ratio of subsequent myocardial disease and shorter life expectancy. Further studies are needed to determine causality and whether AF could be used as a risk marker among particularly younger patients.

Association of Race and Ethnicity With High Longevity Deceased Donor Kidney Transplantation Under the US Kidney Allocation System

Rationale & ObjectiveThe US Kidney Allocation System (KAS) prioritizes candidates with ≤20% Estimated Post-Transplant Survival (EPTS) for high longevity kidneys defined by a ≤20% Kidney Donor Profile Index (KDPI). Use of EPTS in the KAS deprioritizes candidates with older age, diabetes, and longer dialysis durations. We assessed whether this use also disadvantages racial-ethnic minority candidates, who are younger but more likely to have diabetes and longer durations of kidney failure requiring dialysis. Study DesignObservational cohort study. Setting& Participants: Adult candidates for and recipients of kidney transplantation represented in the Scientific Registry of Transplant Recipients from January 2015 through December 2020. ExposureRace and ethnicity. OutcomesAge-adjusted assignment to ≤20% EPTS, transplantation of a ≤20% KDPI kidney, and post-transplant survival in longevity matched recipients by racial-ethnicity. Analytic ApproachMultivariable logistic regression, Fine-Gray competing risks survival analysis, and Kaplan-Meier and Cox Proportional Hazards methods. ResultsThe cohort included 199,444 candidates (7% Asian, 29% Black, 19% Hispanic/Latino, 43% White) listed for deceased donor kidney transplantation. Non-White candidates had significantly higher rates of diabetes, longer dialysis duration, and were younger than White candidates. Adjusted for age, Asian, Black, and Hispanic/Latino candidates had significantly lower odds of having a ETPS score ≤20% (OR 0.86, [0.81, 0.91], 0.52 [0.50, 0.54], and 0.49, [0.47, 0.51]), and were less likely to receive a ≤20% KDPI kidney (subHR 0.70 [0.66, 0.75], 0.89 [0.87, 0.92], and 0.73 [0.71, 0.76]), compared to White candidates. Among recipients with ≤20% EPTS scores transplanted with a ≤20% KDPI deceased donor kidney, Asian and Hispanic recipients had lower post-transplant mortality (HR 0.45 [0.27, 0.77], and 0.63 [0.47, 0.86]) and Black recipients had higher but not statistically significant post-transplant mortality (HR 1.22 [0.99, 1.52]) compared to White recipients. LimitationsProvider reported race-ethnicity data and 5-year post transplant follow-up period. ConclusionsThe US kidney allocation system is less likely to identify racial-ethnic minority candidates as having a ≤20% EPTS score which triggers allocation of high longevity deceased donor kidneys. These findings should inform the OPTN about how to remedy racial/ethnic disparities introduced through KAS’s current approach of allocating allografts with longer predicted longevity to recipients with longer estimated post-transplant survival.

Cancer incidence, type, and survival after bariatric surgery

BackgroundMany types of cancer have been found to be associated with being overweight or obese. Literature has demonstrated a reduction in cancer risk in patients who have undergone bariatric surgery. ObjectivesTo compare the incidence and types of new cancer diagnoses, cumulative cancer incidence, cancer risk, and overall survival in patients with obesity who underwent bariatric surgery with that of those who did not. SettingCommunity-based academic medical center. MethodsWe retrospectively compared the rates and types of new incident cancers in a bariatric surgery cohort (Bariatric group) with those of a non-surgical cohort (Comparison group). The Comparison group was chosen from patients who had a clinic visit in our health system within 30 days of each bariatric surgical operation and matched on age, sex, and body mass index. Patients who had a cancer diagnosis prior to having bariatric surgery were excluded from the Bariatric group and patients who had a cancer diagnosis prior to the clinic visit on which they were matched were excluded from the Comparison group. Relative risk of cancer by type was calculated. Chi-square and Fisher exact tests were used for categorical data analysis, and Wilcoxon rank-sum for continuous data. The Kaplan Meier estimator with the log-rank test was used to compare overall survival between groups, while competing risks survival analysis with the Gray test for equality was used to compare cancer incidence in the Surgery group with that in the Comparison group. ResultsAfter matching, the Bariatric group had 1593 patients and the Comparison group had 2156. The Bariatric and Comparison groups had 82 and 222 new incident cancer cases, respectively (P < .001). The 10-year incidence of any new cancer in the Bariatric group was 6.5%, compared with an incidence of 12.1% in the Comparison group (P < .001). Relative risk of cancer in the Bariatric group was lower than that of the Comparison group, with the greatest differences in endometrial (88.8%), kidney (77.4%), thyroid (72.9%), and ductal carcinoma in situ (71.2%) cancers. The 10-year overall survival rate was higher in the Bariatric group than in the Comparison group, 93.3% versus 80.6%, respectively (P < .001). ConclusionsBariatric surgery reduces the risk for developing cancer and offers survival advantage when compared with similar patients who do not undergo bariatric surgery.

Healing and long-term prognosis of root-fractured permanent teeth: a retrospective longitudinal study.

The purpose of the present study was to evaluate permanent teeth with post-traumatic transversal root fractures, for their initial healing modality, the effect of candidate predictors and their long-term prognosis. A retrospective longitudinal clinical study was conducted to evaluate records from patients bearing transversal root fractures in permanent teeth in order to radiographically assess short-term healing and non-healing events in the fracture line, their prognostic factors and their relationship with long term outcomes. The inter-fragmentary tissues were classified as healing: hard tissue (HT), connective tissue (CT) or connective tissue and bone (CT + B) and non-healing: interposition of granulation tissue (GT). A competing risk survival analysis was conducted to estimate the hazards of healing and non-healing events in the short-term and the effect of demographic, clinical, and treatment variables was assessed using the subdistribution regression model (Fine & Gray). Radiographic findings showed 61.4% of healing in the short-term being strongly influenced by the presence and type of concomitant injuries to the coronal fragment. Teeth with concomitant crown fractures (sHR 24.38, 95% CI [3.16-188.3], p = 0.0022), luxations with dislocations (sHR 10.58, 95% CI [1.37-81.9], p = 0.0240) and subluxations (HR 9.66, 95% CI [1.14-81.7], p = 0.0370) were more likely to present non-healing of root fractures in the short-term. The healing rate in the long-term was of 75.9%, most of them with interposition of bone and connective tissue. Kappa statistics demonstrated an overall agreement of 67.1% between short and long-term healing patterns, in special HT and CT + Bone modalities. Healing at the fracture site was the most frequent outcome, both in the short-term and in the long-term. Short-term healing modality was strongly influenced by the presence and type of concomitant injuries to the crown fragment, being the worst prognosis observed in root-fractured teeth with concomitant crown fractures, followed by concomitant luxations with dislocation. Post-traumatic transversal root fractures have a positive prognosis supporting therefore, a more conservative approach for these teeth before considering more radical treatments.

Probability of default for lifetime credit loss for IFRS 9 using machine learning competing risks survival analysis models

This study introduces a machine learning competing risks survival analysis model aiming at exploring the Probability of Default component of credit risk. Due to modeling of a cumulative probability of default over time, the model is applicable to assess Lifetime Expected Credit Loss under the International Financial Reporting Standard (IFRS) 9 regulation for financial institutions. Whilst most credit models focus on the default event itself, in many loan transactions, there is a competing event affecting risk: the possibility of the borrower prepay their debt before maturity. In this case, credit risk ceases to exist. We derive a statistical model that supports handling competing risks (credit risk and prepayment risk) in a machine learning survival analysis setup. As there is no available implemented computer package or library, we build the computational algorithm with subdistribution hazards using boosting as an ensemble method and componentwise least square models as base learners. Results of the model are generated using a dataset of credit card refinancing operations of a US financial institution. We observe, comparing different survival analysis techniques, that ComponentWise Gradient Boosting (CWGB) models showed competetive performance on both scenarios (subdistribution hazards and cause-specific models) compared to benchmark models. The derived model is useful to address the guidelines of the IFRS 9 for credit risk, taking into account the context of lifetime credit exposure.

A retrospective cohort study of pulp prognosis in luxated permanent teeth: a competing risk analysis.

The present retrospective cohort study aimed to evaluate luxated permanent teeth for pulp prognosis and risk factors. Case records and radiographs of 224 patients, involving 427 luxated permanent teeth, referred for treatment at the Dental Trauma Center-School of Dentistry, Universidade Federal de Minas Gerais, (DTC-SD-UFMG) from 2014 to 2022, were assessed for pulp prognosis classified as vitality, necrosis and pulp canal obliteration (PCO). A competing risk survival analysis estimated the hazards of the three outcomes, and the effect of demographic, clinical and treatment variables was tested using a cause specific Cox regression model. Pulp vitality was found in163 teeth (38.2%), pulp necrosis in 120 teeth (28.1%) and 55 teeth (12.9%) developed PCO. Pulp vitality decreased in the presence of concomitant crown fractures (HR 0.38 95% CI [0.2-0.8] p = 0.006). The risk of pulp necrosis (HR 0.62 95% CI [0.4-0.96] p = 0.03) was lower in cases with open apices but increased with concomitant crown fractures (HR 4.0 95% CI [2.6-6.1] p = 0.001) and intrusions (HR 2.3 95% CI [1.2-4.1] p = 0.007). Lateral or extrusive luxations (HR 3.0 95% CI [1.3-6.9] p = 0.001) and open apices (HR 2.4 95% CI [1.2-4.7] p = 0.01) showed higher rates of PCO. Type of luxation, the diameter of the apical foramen, and the presence of concomitant crown fractures were main determinants of pulp prognosis after luxation injuries in permanent teeth. Pulp prognosis after tooth luxation is dependent on the presence and direction of tooth displacement together with infection control. Not applicable.

Inpatient admissions and mortality of anorexia nervosa patients according to their preceding psychiatric and somatic diagnoses.

Anorexia nervosa (AN) is associated with increased risk of mortality, but little is known about the risk of inpatient admissions and mortality outcomes in individuals with diagnoses of both AN and other psychiatric and somatic conditions. We aimed to investigate the inpatient admissions and mortality among people with AN and other diagnosed conditions using Danish national registers. This retrospective cohort study included individuals diagnosed with AN in Denmark, born 1977-2010. We identified other mental and somatic conditions in this population. We used Cox proportional hazards regression to estimate the risk of inpatient admission and mortality, focusing on (i) the number of other diagnosed conditions, and (ii) specific combinations of conditions diagnosed prior to the AN diagnosis. Categories of inpatient admissions considered were due to: (i) AN, (ii) any psychiatric disorder, and (iii) any somatic disorder. Additionally, competing risks survival analysis was used to calculate the cumulative incidence of inpatient admission and all-cause mortality over the follow-up period. The study population included 11,489 individuals. The most common conditions individuals had prior to their AN diagnosis were other eating disorders (34.5%) and anxiety disorders (32.7%). During the follow-up, 3184 (27.7%), 4604 (40.1%), and 6636 (57.8%) individuals were admitted for AN, any psychiatric disorder, and any somatic disorder, respectively; and in total 106 (0.9%) died. The risk of all outcomes was highest among those who had received a higher number of other diagnoses. For most combinations, the risks of admission and mortality were increased. Our study presents the prevalence of other conditions in patients with AN in Denmark and elucidates their association with higher rates of inpatient admission and mortality. Our findings highlight the need for comprehensive, multidisciplinary care of patients with AN considering the spectrum of other diagnosed conditions to improve health outcomes.

Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost

BackgroundThoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed.ObjectiveWe aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age.MethodsWe identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis.Results1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2–22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2–1.02) for 75-year old patients.ConclusionIn patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.

A comparison between two systems of university education: years of study versus credit accumulation

ABSTRACT A recent major reform of higher education has changed a year-based system into a credit accumulation one. We use this exogenous shock to compare the two systems. Using a longitudinal dataset of undergraduate students from one of the largest French-speaking universities, a competing risks survival analysis is performed to study the probabilities and duration to graduation or dropout. The results indicate that the credit accumulation system encourages students to be less engaged in their studies, at the cost of late graduation in the best case, and in the worst case, late dropout which affects mostly students coming from disadvantaged backgrounds.

Risk factors for COVID-19 in-hospital mortality in Argentina: A competing risk survival analysis.

COVID-19 poses dire threats for low and middle-income countries (LMICs). Yet, there remains limited rigorous evidence describing the characteristics and outcomes of hospitalized patients for LMICs, and often the evidence was based on small samples and/or unicentric. The objective of this study was to examine risk factors of COVID-19 mortality in Argentina, a hard-hit middle-income Latin American country. We analyze data on 5,146 COVID-19 patients from 11 centers across 10 cities in Argentina, making this one of the largest multi-centric retrospective observational descriptive studies in the LMICs. Information on demographics and co-morbidities was extracted from medical records. Outcomes of relevance consisted of whether the patient was discharged or deceased (as established in medical records), along with date of each event. We use survival models that account for competing risks. Median age was 60 years (IQR: 48-72), there were fewer women (40.8%) hospitalized than men (59.2%), and the most prevalent comorbidities were hypertension (40.9%), diabetes (20.0%) and obesity (19.1%). Patients were hospitalized for a median duration of 8 days (IQR: 5-13), and in-hospital mortality was 18.1%, though it varied substantially across health centers (95%CI: 17.1%-19.2%). Baseline characteristics most associated with in-hospital mortality were respiratory rate (adjusted HR = 3.6, 95%CI: 2.5-5.4 for ≥ 26 breathes/min), older age (adjusted HR = 2.5, 95%CI: 2.0-3.3 for the 80+ age group), and chronic kidney disease (adjusted HR = 2.2, 95%CI: 1.8-2.8). Associations were attenuated when survival models did not account for the competing risk of being discharged. We document lower mortality rates than those in prior studies, likely due to a lower prevalence of comorbidities amongst patients in our sample. Compared with standard Cox models, we find that, when using competing risk models, risk factors have a larger role in explaining COVID-19 mortality. Overall, we provide rigorous evidence describing the characteristics and outcomes of hospitalized patients for LMICs. Thus, our findings are useful to conduct a more accurate in-hospital monitoring of patient subgroups who may be at greater risk. They also provide valuable guidance for public health and policy efforts in Argentina and other developing countries.

Association of serum 25-hydroxyvitamin D with cardiovascular and all-cause mortality in patients with chronic kidney disease: NHANES 2007‒2018 results

BackgroundVitamin D insufficiency is a prevalent issue in patients suffering from CKD. The purpose of this study was to determine whether serum 25(OH)D levels are associated with all-cause and cardiovascular mortality in patients with CKD. MethodsTo examine the associations between 25(OH)D levels and cardiovascular mortality, this retrospective cohort study used the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007‒2018 database. A total of 2,668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. The associations were assessed using Cox proportional hazards regression, restricted cubic splines, Kaplan-Meier survival curves, and competing risks survival analysis. Furthermore, subgroup and sensitivity analyses were performed. ResultsDuring a median follow-up of 72 months in a weighted population of 11,715,452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause mortality (HR= 0.85, 95 % CI 0.77∼0.94) and cardiovascular mortality (SHR= 0.80, 95 % CI 0.67∼0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile). Compared to group Q1, both group Q3 (HR = 0.71, 95 % CI 0.54‒0.93) and group Q4 (HR = 0.72, 95 % CI 0.55‒0.94) exhibited a significantly reduced mortality risk. Weighted restricted cubic splines revealed an inverse J-shaped linear association between levels of 25(OH) D and all-cause mortality ((PNonliner > 0.05). Subgroup analysis and sensitivity analysis yielded similar findings. ConclusionsAll-cause mortality and cardiovascular disease-related mortality were significantly increased by lower 25(OH)D levels, both as continuous and categorical variables. 25(OH)D has an inverse J-shaped linear association with all-cause and cardiovascular mortality.

Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost.

We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification. 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included. Competing risk survival analyses to compare individuals with CAPRA scores < 6 vs. ≥ 6 for biochemical relapse (BCR) and metastasis incidence were conducted. Also, overall survival (OS) for both groups using Kaplan-Meier analysis was assessed. The same analyses were repeated using a 5-tier NCCN stratification comparing those classified as high-risk vs. very high-risk patients. The median age was 71 years, and the median follow-up period was 72 months. The whole cohort received an EQD2 of 74 Gy or greater, with a median EQD2 of 106.89 Gy. Both a CAPRA score ≥ 6 and belonging to the NCCN very high-risk group were associated with BCR, with subdistribution hazard ratios (sHRs) of 3.04 (p = 0.015) and 2.53 (p = 0.013), respectively. For metastasis incidence, both the CAPRA and NCCN groups had similar sHRs of 2.60 (p = 0.094) and 2.71 (p = 0.037), respectively. For 10-year OS, patients with CAPRA score ≥ 6 and belonging to the NCCN very high-risk group presented similar HRs of 2.11 (p = 0.005) and 2.10 (p = 0.002). We showed that high-risk PCa patients classified according to the 3-tier NCCN system benefit from further stratification using the CAPRA score or the 5-tier NCCN stratification method. Patients with a CAPRA score ≥ 6 or classified as very high-risk demonstrate a higher hazard of BCR, metastasis, and death. These patients might benefit from further intensification of their investigations and treatment, based on ongoing research.

Outcomes of SARS-CoV-2 and Seasonal Viruses Among Children Hospitalized in Brazil.

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with other respiratory viruses is crucial for developing effective public health strategies in the postpandemic era. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in children and adolescents hospitalized with severe acute respiratory infection (SARI). This population-based, retrospective cohort study included children and adolescents hospitalized with SARI from February 2020 to February 2023 in Brazil. The main exposure of interest was viral etiology. The primary outcome was in-hospital mortality. Competing risk analysis was used to account for time dependency and competing events. A total of 235 829 patients had available results of the viral tests, with SARS-CoV-2 predominance. According to the competing-risk survival analysis, the estimated probability of a fatal outcome at 30 days of hospitalization according to the viral strain was 6.5%, 3.4%, 2.9%, 2.3%, 2.1%, and 1.8%, for SARS-CoV-2, coinfection, adenovirus, influenza, other viruses, and respiratory syncytial virus, respectively. Individuals with a positive test for SARS-CoV-2 had hazard of death 3 times higher than subjects with a negative test (hazard ratio, 3.3; 95% confidence interval, 3.1-3.5). After adjustment by the competing-risk multivariable analysis, admission in Northeast and North regions, oxygen saturation <95%, and the presence of comorbidities were risk factors for death in all viral strains. SARS-CoV-2 infection had the highest hazard of in-hospital mortality in this pediatric cohort hospitalized with SARI. Regardless of viral etiology, the presence of underlying medical conditions was a risk factor for death.

Long-term neuropsychiatric sequelae of Delta versus Omicron SARS-CoV-2 infection

ObjectivesStudies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre–specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. MethodsThe national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. Results104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12–1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39–1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78–7.41) and psychosis (aHR, 1.65; 95% CI, 1.22–2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32–2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. DiscussionsA modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection.

Rotational thromboelastometry as a biomarker for mortality — The Maastricht Intensive Care COVID cohort

BackgroundPatients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. MethodsPatients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. ResultsOf the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8–24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. ConclusionsROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.

Are breast cancer patients with suboptimal adherence to cardiovascular treatment more likely to discontinue adjuvant endocrine therapy? Competing risk survival analysis in a nationwide cohort of postmenopausal women

BackgroundHigh rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the successful management of cardiovascular risk, which affects a high proportion of postmenopausal women. As with AET, adherence with cardiovascular drugs is suboptimal. We examined whether patient adherence with cardiovascular drugs was associated with the rate of AET discontinuation in a French nationwide claims database linked with hospitalisation data.MethodsWe identified postmenopausal women starting AET between 01/01/2016 and 31/12/2020 and taking at least two drugs for the primary prevention of cardiovascular disease (antihypertensive drugs, lipid-lowering drugs and platelet aggregation inhibitors) before AET initiation. Adherence was assessed for each drug class by computing the proportion of days covered. Women were categorised as fully adherent, partially adherent or fully non-adherent with their cardiovascular drug regimen based on whether they adhered with all, part or none of their drugs. AET discontinuation was defined as a 90-day gap in AET availability. Time to AET discontinuation according to levels of cardiovascular drug adherence was estimated using cumulative incidence curves, accounting for the competing risks of death and cancer recurrence. Multivariate cause-specific Cox regressions and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation.ResultsIn total, 32,075 women fit the inclusion criteria. Women who were fully adherent with their cardiovascular drugs had the lowest cumulative incidence of AET discontinuation at any point over the 5-year follow-up period. At 5 years, 40.2% of fully non-adherent women had discontinued AET compared with 33.5% of partially adherent women and 28.8% of fully adherent women. Both partial adherence and full non-adherence with cardiovascular drugs were predictors of AET discontinuation in the two models (cause-specific hazard ratios 1.16 [95% CI 1.10–1.22] and 1.49 [95% CI 1.39–1.58]; subdistribution hazard ratios 1.15 [95% CI 1.10–1.21] and 1.47 [95% CI 1.38–1.57]).ConclusionClinicians should be aware that patients who do not adhere with their entire cardiovascular drug regimen are also more likely to discontinue AET. This stresses the importance of integrated care, as suboptimal adherence with both treatment components poses a threat to achieving ideal patient outcomes.