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Background: Ex vivo lung perfusion (EVLP) is a method for the evaluation and reconditioning of high‐risk donor lungs to increase the pool of potential donor lungs. Methods: We reviewed all consecutive patients who received lung transplants from May 2012 to May 2017 with follow‐up until July 2021. EVLP was used in lungs initially rejected due to inadequate oxygenation but without other contraindications. Lungs with improved oxygenation levels above the threshold were transplanted. The primary endpoint was the time to graft failure, which was defined as the time from surgery to death or re‐transplantation, whichever occurred first. The secondary outcome was freedom from chronic lung allograft dysfunction. Results: A total of 157 patients underwent transplantation during the study period. Thirty‐nine patients received EVLP‐treated donor lungs. Restricted mean graft survival time up to 7 years is 5.14 years for non‐EVLP and 4.19 for EVLP, the difference being −0.95 (confidence interval [CI]—1.93 to 0.04, p =.059). The hazard ratio is 1.66 (CI 1.00–2.75, p =.046). Chronic lung allograft dysfunction was the highest contributor to mortality in both groups. There were significant differences in freedom from chronic lung allograft dysfunction at 12 and 24 months of follow‐up (p =.005 and p =.030, respectively). Subgroup analyses revealed that the first patients who received EVLP in 2012–2013 had a substantially worse 5‐year graft survival than those who received EVLP more recently in 2016–2017 (14.3% vs. 60.0%). For the latter, the 5‐year graft survival was observed to be remarkably close to the non‐EVLP group (60.8%). Conclusion: Long‐term survival was significantly lower, and lung function was poorer among recipients in the EVLP group than in the non‐EVLP group. However, the outcome of patients who received EVLP‐treated lungs was observed to improve steadily after the first 2 years after EVLP was introduced in Denmark. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between previous periodontal treatment and recurrent events after first‐time myocardial infarction (MI). Materials and Methods: From the Danish nationwide registries, patients with first‐time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first‐time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3‐year risk of major adverse cardiovascular events (MACE). Results: A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first‐time MI had an adjusted 3‐year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92–1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3‐year risks of MACE (OR 1.47 [95% CI 1.42–1.52]), cardiovascular death (OR 1.71 [95% CI 1.64–1.78]) and heart failure (OR 1.13 [95% CI 1.07–1.20]) compared with patients presumed periodontally healthy. Conclusions: Patients with treated PD 1 year prior to first‐time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first‐time MI was an independent risk factor for recurrent events. [ABSTRACT FROM AUTHOR]

Several studies for the clinical validity of circulating tumor cells (CTCs) in metastatic breast cancer were conducted showing that it is a prognostic biomarker of overall survival. In this work, we consider an individual patient data meta-analysis for nonmetastatic breast cancer to assess the discrimination of CTCs regarding the risk of death. Data are collected in several centers and present correlated failure times for subjects of the same center. However, although the covariate-specific time-dependent receiver operating characteristic (ROC) curve has been widely used for assessing the performance of a biomarker, there is no methodology yet that can handle this specific setting with clustered censored failure times. We propose an estimator for the covariate-specific time-dependent ROC curves and area under the ROC curve when clustered failure times are detected. We discuss the assumptions under which the estimators are consistent and their interpretations. We assume a shared frailty model for modeling the effect of the covariates and the biomarker on the outcome in order to account for the cluster effect. A simulation study was conducted and it shows negligible bias for the proposed estimator and a nonparametric one based on inverse probability censoring weighting, while a semiparametric estimator, ignoring the clustering, is markedly biased. Finally, in our application to breast cancer data, the estimation of the covariate-specific area under the curves illustrates that the CTCs discriminate better patients with inflammatory tumor than patients with noninflammatory tumor, with respect to their risk of death. [ABSTRACT FROM AUTHOR]

Summary: One of the objectives of personalized medicine is to take treatment decisions based on a biomarker measurement. Therefore, it is often interesting to evaluate how well a biomarker can predict the response to a treatment. To do so, a popular methodology consists of using a regression model and testing for an interaction between treatment assignment and biomarker. However, the existence of an interaction is not sufficient for a biomarker to be predictive. It is only necessary. Hence, the use of the marker‐by‐treatment predictiveness curve has been recommended. In addition to evaluate how well a single continuous biomarker predicts treatment response, it can further help to define an optimal threshold. This curve displays the risk of a binary outcome as a function of the quantiles of the biomarker, for each treatment group. Methods that assume a binary outcome or rely on a proportional hazard model for a time‐to‐event outcome have been proposed to estimate this curve. In this work, we propose some extensions for censored data. They rely on a time‐dependent logistic model, and we propose to estimate this model via inverse probability of censoring weighting. We present simulations results and three applications to prostate cancer, liver cirrhosis, and lung cancer data. They suggest that a large number of events need to be observed to define a threshold with sufficient accuracy for clinical usefulness. They also illustrate that when the treatment effect varies with the time horizon which defines the outcome, then the optimal threshold also depends on this time horizon. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the risk of heart failure (HF) in patients with type 2 diabetes (T2D) complicated by development of intercurrent ischaemic heart disease (IHD), end-stage renal disease (ESRD), or both, compared to patients with T2D and no IHD and ESRD.Methods and Results: From Danish nationwide registries, we identified all patients with new-onset T2D with no history of HF between 1998 and 2015. Landmark analyses were used to estimate the 5-year absolute risk of HF at several follow-up times, and accounted for the occurrence of IHD and ESRD, identified before HF. The Aalen-Johansen estimator was used to account for censoring and the competing risk of death. A total of 285 024 patients with new-onset T2D were included. During follow-up, 19 960 developed incident HF. Among patients with T2D free of HF 5 years after T2D diagnosis, patients without IHD and ESRD had the lowest 5-year risk of HF [4.02%; 95% confidence interval (CI) 3.90-4.15), those with T2D complicated by IHD [11.51%; relative risk (RR) 2.86; 95% CI 2.72-3.02; P < 0.001] or ESRD (8.11%; RR 2.02; 95% CI 1.39-2.93; P < 0.001) an intermediate risk, and those with both IHD and ESRD (19.76%; RR 4.92; 95% CI 3.43-7.05; P < 0.001) the highest risk.Conclusion: Patients with T2D complicated by development of intercurrent IHD, ESRD, or both, showed a significantly higher risk of HF compared to those who did not develop IHD and ESRD. An effective way to delay or prevent the development of HF in patients with T2D may be to prevent IHD and ESRD. [ABSTRACT FROM AUTHOR]

In the context of chronic diseases, patient's health evolution is often evaluated through the study of longitudinal markers and major clinical events such as relapses or death. Dynamic predictions of such types of events may be useful to improve patients management all along their follow-up. Dynamic predictions consist of predictions that are based on information repeatedly collected over time, such as measurements of a biomarker, and that can be updated as soon as new information becomes available. Several techniques to derive dynamic predictions have already been suggested, and computation of dynamic predictions is becoming increasingly popular. In this work, we focus on assessing predictive accuracy of dynamic predictions and suggest that using an R2 -curve may help. It facilitates the evaluation of the predictive accuracy gain obtained when accumulating information on a patient's health profile over time. A nonparametric inverse probability of censoring weighted estimator is suggested to deal with censoring. Large sample results are provided, and methods to compute confidence intervals and bands are derived. A simulation study assesses the finite sample size behavior of the inference procedures and illustrates the shape of some R2 -curves which can be expected in common settings. A detailed application to kidney transplant data is also presented. [ABSTRACT FROM AUTHOR]

Background/aims: Intrusive luxation is a frequent injury in the primary dentition. Complications such as ankylosis or pulp necrosis (PN) and infection with periapical inflammation may affect the developing permanent tooth if not diagnosed and treated in time. The aim of this study was to report the risk of PN, pulp canal obliteration (PCO), infection-related resorption (IRR), ankylosis-related resorption (ARR) and premature tooth loss (PTL) in primary teeth following intrusive luxation, and to identify possible risk factors for PN and PTL.Materials and Method: A retrospective analysis of a cohort comprising 149 patients 194 intruded primary incisors. No treatment was performed. The follow-up programme included examination after 4 weeks, 8 weeks, 6 months, 1 year, and at 6 years of age. The minimum follow-up period was 1 year or until time of tooth loss.Statistics: The Kaplan-Meier and Aalen-Johansen methods were employed along with Cox regression analysis. The level of significance was 5%.Results: Risks estimated after 3 years: PCO 38.9% (95% CI: 31.8-46.0), PN 24.2% (95% CI: 17.7-30.6), IRR 8.8% (95% CI: 4.5-13.1), ARR 3.6% (95% CI: 1.0-6.2) and PTL 39.4% (95% CI: 31.2-47.5). Most teeth (83.7%) spontaneously re-erupted within the first year. Most complications were diagnosed within the first year. The risk of PN was lowest in patients less than 2 years of age. The degree of intrusion or a concomitant crown fracture did not affect the risk of PN or PTL.Conclusions: Over 80% of the intruded primary teeth re-erupted spontaneously. However, nearly one-third of the teeth showed complications such as pulp infection/periapical inflammation or ankylosis, which could potentially affect the development of the permanent incisor. Therefore, patients should be monitored regularly, especially during the first year after injury, to diagnose and treat complications in time. [ABSTRACT FROM AUTHOR]

Background/aim: Traumatic dental injuries in the primary dentition occur frequently. Long-term complications may potentially cause damage to the permanent successor. The aim of this study was to report the risk of pulp necrosis (PN), pulp canal obliteration (PCO), repair-related resorption (RRR), infection-related resorption (IRR), ankylosis-related resorption (ARR), and premature tooth loss (PTL) in primary teeth following concussion and subluxation injuries, and to identify possible risk factors for PN, PCO, and PTL following subluxation.Material and Methods: The study was a retrospective analysis of a cohort comprising 31 patients (36 teeth) with concussion injury and 174 patients (241 teeth) with subluxation injury. No treatment was performed. The follow-up program included examination after 4 weeks, 8 weeks, 6 months, 1 year, and when the patients were 6 years of age. Minimum follow up was 1 year or until the time of tooth loss.Statistics: Kaplan-Meier and Aalen-Johansen methods and Cox regression analysis. Level of significance was set at 5%.Results: Risk estimated after one year. Concussion: PCO 8.6% (95% CI: 0-17.9), PN 5.7% (95% CI: 0-13.4), PTL 5.6% (95% CI: 0-13.4). Subluxation: PCO 23.2% (95% CI: 17.8-28.6), PN 8.3% (95% CI: 4.8-11.8), IRR 2.6% (95% CI: 0.5-4.6), PTL 9.5% (95% CI: 5.0-14.1). Most complications (95%) were diagnosed within the first year. Most cases of PN (65%) and PTL (85%) were seen in patients aged 4 years or more.Conclusion: Primary teeth with concussion or subluxation injury carry a low risk of PN and infection with periapical inflammation, root resorption, and PTL. Nearly all complications were diagnosed within the first year after the injury. The risk of PTL was highest in patients more than 4 years of age at the time of injury. [ABSTRACT FROM AUTHOR]

Background/aim: Traumatic dental injuries (TDI) in the primary dentition occur frequently. Long-term complications may potentially cause damage to the permanent successor. The aim of this study was to report the risk of pulp necrosis (PN), pulp canal obliteration (PCO), infection-related resorption (IRR), ankylosis-related resorption (ARR) and premature tooth loss (PTL) in primary teeth following extrusion or lateral luxation and to identify risk factors for PN and PTL.Material and Methods: This was a retrospective study of 24 patients with 26 extruded primary teeth and 242 patients with 331 primary teeth with lateral luxation. Laterally luxated teeth were left without treatment. Extruded teeth were repositioned. Follow up included examination after 4 weeks, 8 weeks, 6 months, 1 year and when the patients were 6 years old. The minimum follow up was 1 year or until tooth loss. Kaplan-Meier and Aahlen-Johansson tests were used along with Cox regression analysis. The level of significance was 5%.Results: Risk estimated after 3 years-Extrusion: PCO 39.8% (95% CI: NA), PN 15.6% (95% CI: 1.5-29.7), IRR 3.8% (95% CI: 0-11.2) and PTL 43.3% (95% CI: 25.5-61.2). All cases of PN and PTL occurred within the first year. Lateral luxation: PCO 41.3% (CI: 95% 35.7-46.9), PN 19.8% CI: 95% (15.3-24.2), IRR 7.0% (95% CI: 4.1-9.8), ARR 1.4% (95% CI: 0-3.3) and PTL 24.8% (95% CI: 18.8-30.8). Risk factors for PN: concomitant crown fracture and patient aged 4 years or more. Nearly all teeth (95%) realigned spontaneously within the first year. Nearly all cases of PN and PTL (95.7%) occurred within the first year.Conclusion: The healing potential for laterally luxated teeth was high and more than half of the extruded teeth, which were repositioned after injury, showed long-term survival. [ABSTRACT FROM AUTHOR]

Aims Patients with heart failure in sinus rhythm are at an increased risk of thromboembolic complications. So far, validated risk stratification tools are lacking for such patients, which makes the decision to initiate anti-thrombotic treatment difficult. Methods and results We included 136 545 patients admitted with heart failure in sinus rhythm from national registries from 1999 to 2012. Patients receiving oral anticoagulants were omitted from the study. First, we investigated if the CHA2DS2-VASc score could identify heart failure patients in sinus rhythm with high rates of thromboembolic complications. Second, we investigated if any single CHA2DS2-VASc risk factor carried a greater prognostic value with regard to thromboembolism. The risk of thromboembolism increased more than ninefold (hazard ratio 9.2, 95% confidence interval 6.8-12.5) in patients with all CHA2DS2-VASc risk factors compared with those with heart failure alone. The incidence rates of thromboembolism were clinically significant, averaging 6.0 (95% confidence interval 5.98-6.02) events per 100 patient years during the first year following diagnosis. Risk factors such as diabetes, age, vascular disease, and especially previous thromboembolism, conferred an independent risk of future thromboembolism. Conclusion The CHA2DS2-VASc risk stratification scheme was able to provide prognostic information on future thromboembolic events in patients with heart failure in sinus rhythm. The CHA2DS2-VASc scale could be easily implemented as an aid to clinicians in risk stratifying heart failure patients in sinus rhythm, for thromboembolism. [ABSTRACT FROM AUTHOR]

The area under the time-dependent ROC curve (AUC) may be used to quantify the ability of a marker to predict the onset of a clinical outcome in the future. For survival analysis with competing risks, two alternative definitions of the specificity may be proposed depending of the way to deal with subjects who undergo the competing events. In this work, we propose nonparametric inverse probability of censoring weighting estimators of the AUC corresponding to these two definitions, and we study their asymptotic properties. We derive confidence intervals and test statistics for the equality of the AUCs obtained with two markers measured on the same subjects. A simulation study is performed to investigate the finite sample behaviour of the test and the confidence intervals. The method is applied to the French cohort PAQUID to compare the abilities of two psychometric tests to predict dementia onset in the elderly accounting for death without dementia competing risk. The 'timeROC' R package is provided to make the methodology easily usable. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To quantify the ability of a marker to predict the onset of a clinical outcome in the future, time-dependent estimators of sensitivity, specificity, and ROC curve have been proposed accounting for censoring of the outcome. In this paper, we review these estimators, recall their assumptions about the censoring mechanism and highlight their relationships and properties. A simulation study shows that marker-dependent censoring can lead to important biases for the ROC estimators not adapted to this case. A slight modification of the inverse probability of censoring weighting estimators proposed by Uno et al. (2007) and Hung and Chiang (2010a) performs as well as the nearest neighbor estimator of Heagerty et al. (2000) in the simulation study and has interesting practical properties. Finally, the estimators were used to evaluate abilities of a marker combining age and a cognitive test to predict dementia in the elderly. Data were obtained from the French PAQUID cohort. The censoring appears clearly marker-dependent leading to appreciable differences between ROC curves estimated with the different methods. [ABSTRACT FROM AUTHOR]

Background Potassium disturbances per se increase the risk of ventricular fibrillation (VF). Whether potassium disturbances in the acute phase of ST-segment-elevation myocardial infarction (STEMI) are associated with VF before primary percutaneous coronary intervention (PPCI) is uncertain. Methods and Results All consecutive STEMI patients were identified in the Eastern Danish Heart Registry from 1999 to 2016. Comorbidities and medication use were assessed from Danish nationwide registries. Potassium levels were collected immediately before PPCI start. Multivariate logistic models were performed to determine the association between potassium and VF. The main analysis included 8624 STEMI patients of whom 822 (9.5%) had VF before PPCI. Compared with 6693 (77.6%) patients with normokalemia (3.5-5.0 mmol/L), 1797 (20.8%) patients with hypokalemia (<3.5 mmol/L) were often women with fewer comorbidities, whereas 134 (1.6%) patients with hyperkalemia (>5.0 mmol/L) were older with more comorbidities. After adjustment, patients with hypokalemia and hyperkalemia had a higher risk of VF before PPCI (odds ratio 1.90, 95% CI 1.57-2.30, P <0.001) and (odds ratio 3.36, 95% CI 1.95-5.77, P <0.001) compared with normokalemia, respectively. Since the association may reflect a post-resuscitation phenomenon, a sensitivity analysis was performed including 7929 STEMI patients without VF before PPCI of whom 127 (1.6%) had VF during PPCI. Compared with normokalemia, patients with hypokalemia had a significant association with VF during PPCI (odds ratio 1.68, 95% CI 1.01-2.77, P =0.045) after adjustment. Conclusions Hypokalemia and hyperkalemia are associated with increased risk of VF before PPCI during STEMI. For hypokalemia, the association may be independent of the measurement of potassium before or after VF.