Time-dependent Occurrence Research Articles

Risk-Targeted Seismic Design Maps with Aleatory and Epistemic Uncertainty in Tehran and Surrounding Areas

ABSTRACT This study aims to introduce a risk-targeted probabilistic model that facilitates seismic design hazard mapping. Here, we investigate how to incorporate hazard regional variations and different structural fragility typologies so as to achieve a uniform target risk across the map. This paper takes Tehran, the capital city, and its surrounding area as a case study and explores the highly digitized hazard curves conditioned on the time-dependent occurrence of an earthquake at a 50-year exposure time. We introduce a new set of parameterized quantile functions for Risk-targeted design Intensity Measure (IMR) as the seismic design hazard. A group of IMR maps is subsequently prepared based on a 1% collapse probability during the next 50-year lifetime. Furthermore, the quantile function corresponding to each fragility type is able to show the aleatory uncertainty at each site on the region map. The uncertainty maps illustrate relatively less inherent variability than what exists in the hazard curves themselves. Then, we tackle the source of uncertainty arising from percentile hazard curves into IMR, known as epistemic uncertainty, by deriving a new closed-form expression, which allows for a sampling-free estimation of the epistemic uncertainty. The risk-targeted seismic design hazard with its accompanying uncertainties can lead to a promising seismic design hazard with potential applications for the insurance industry, urban planners, and risk-aware building owners.

Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation

ObjectivesSeveral studies have reported the effects of Fusobacterium nucleatum stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the in vitro studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent Fusobacterium nucleatum infection on oral cancer cells. MethodsHuman tongue squamous cell carcinoma (SCC) cells were continuously stimulated with Fusobacterium nucleatum for two or four weeks, then experimentally evaluated. ResultsProlonged, persistent Fusobacterium nucleatum stimulation increased the cells’ proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with Fusobacterium nucleatum for four weeks in the presence of dexamethasone, Fusobacterium nucleatum induced epithelial-mesenchymal transition was inhibited. ConclusionsEpithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent Fusobacterium nucleatum stimulation and inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.

Improving seimic hazard assessment in the Mediterranean Region

This paper is intended as a short presentation of the main limitations affecting seismic hazard assessment, revisiting possible methods available in the literature to be applied for this purpose. The convergence of the African Plate with the Eurasian Plate is the cause of the high seismic activity characterizing the Mediterranean region, with particular intensity in its eastern part. It is clear that the associated seismic risk requires appropriate measures for its mitigation. Seismic risk, the amount of resources that the community is expected to pay to earthquakes in the long term, is the product of three factors, such as seismic hazard, vulnerability and value of the exposed goods. As earthquakes cannot be prevented, seismic risk can be mitigated by improving our knowledge of seismic hazard, which is largely based on statistical analysis of historical earthquake catalogs. Nevertheless, historical records are affected by problems of reliability, completeness and shortness, as they commonly span time lengths of the same order of magnitude or even shorter than the inter-event time of the strongest earthquakes produced by specific seismic sources. In this respect, alternative methods can be proposed for integrating and improving our knowledge of seismogenic processes, and estimating both time-independent and time-dependent occurrence rates of strong earthquakes. We propose the application of physics-based earthquake simulators, requiring the knowledge of a robust geological-geophysical seismogenic model.

High success rate of nocturnal enuresis treatment during the stay-home period for COVID-19.

ObjectivesTo clarify whether enuresis treatment was more effective during the stay‐home period for the coronavirus disease 2019 pandemic, when restrictions on activities enabled patients to concentrate on treatment.MethodsWe performed a retrospective, nonrandomized cohort study for monosymptomatic enuresis during the coronavirus disease 2019 pandemic (March–June 2020) and a 2‐year comparator period (March–June 2018 and March–June 2019). Primary outcome was treatment response, defined as a change in the number of wet nights per week within 6 months following enrollment. The time‐dependent occurrence of treatment response was evaluated with the Kaplan–Meier method and the log‐rank test. The Cox proportional hazards regression model was used to identify risk factors for treatment response. The range of appropriate sample sizes for this primary outcome was 39–48.ResultsOf our 41 enrolled patients, 28 (68%) were male and mean age was 8.8 years. The complete response rate was 73% during the coronavirus disease 2019 pandemic period and 27% during the comparator period. Log‐rank tests showed a higher cumulative incidence of complete response in the pandemic period (P = 0.020). Cox regression analysis identified treatment during the coronavirus disease 2019 pandemic (hazard ratio 2.533; 95% confidence interval 1.069–6.006) and dinner before 19:00 (hazard ratio 4.184; 95% confidence interval 1.56–11.252) as significantly associated with treatment response.ConclusionsThe rate of enuresis treatment response was uncommonly high during the stay‐home period for the coronavirus disease 2019 pandemic. Restrictions on daily life may provide opportunities to concentrate on treatments for chronic illnesses, leading to more success.

Early Allograft Dysfunction Is Associated with Higher Complication Rate after Liver Transplantation

Introduction: Liver transplantation is considered as the standard of care for patients with end-stage liver diseases. However, an early graft dysfunction (EAD) is still one of the many challenges that clinicians have to overcome. EAD has a varying incidence between 10.8% to 36.3% and the association between EAD and worse graft or patient survival rate has been repeatedly reported; however, little has been conducted about the postoperative complications after occurrence of EAD which lead subsequently to higher mortality among EAD patients. Method: We performed a retrospective analysis on patients who underwent liver transplantation from January 2007 to July 2012. For definition of EAD we adopted the Olthoff criteria. All complications were classified in accordance to the time-dependent occurrence as “early”, “intermediate” or “late”. Results: From a total of 555 patients, 214 (38.6%) developed EAD. Both 12 month graft and patient survival rate were significantly worse in EAD patients. Analysis of complications rate showed that EAD patients had higher rate of sepsis (p=0.001), acute renal failure (p<0.001) and bleeding postoperatively (p=0.012). EAD development was associated with higher likelihood for reoperation and retransplantation (p=0.04 and p<0.001). Within first week after transplantation, EAD patients had higher rate of sepsis and postoperative bleeding (p<0.001, p=0.015); however incidences of intermediate and late complications did not differ. Conclusions: Patients who develop EAD have significantly higher rate of early sepsis, postoperative bleeding and acute kidney injury, which constitute worse outcomes. Patients with EAD are more likely to have a reoperation and/or retransplantation.

Patient-Reported Financial Distress in Cancer: A Systematic Review of Risk Factors in Universal Healthcare Systems.

Simple SummaryA comprehensive understanding of risk factors associated with experiencing subjective financial distress is needed to inform the development of valid instruments and effective interventions to tackle financial toxicity. Several studies from the US indicate a strong correlation of the US-healthcare system’s systematic organisation and its particular socioeconomic risk factors for cancer patients experiencing financial toxicity. It is assumed that risk factors differ in other high-income countries due to the different structure of universal healthcare coverage. As an exhaustive analysis for other countries is lacking, this review aims to identify risk factors for subjective financial distress in universal healthcare systems.Financial toxicity is a side effect of cancer that results from the perceived financial distress an individual may experience in the course of the disease. The purpose of this paper is to analyse underlying factors related to subjective financial distress in high-income countries with universal healthcare coverage. A systematic literature review was conducted to identify qualitative and quantitative studies of cancer patient-reported subjective financial distress by performing a search in the databases of PubMed, PsycINFO and CINAHL up to December 2020. A qualitative synthesis was performed linking the time-dependent occurrence of risk factors to derived categories of risk factors. Out of 4321 identified records, 30 quantitative and 16 qualitative studies were eligible. Classification of risk factors resulted in eight categories with a total of 34 subcategories. Subjective financial distress is primarily determined by pre-diagnosis sociodemographic- factors as well as financial and work factors that might change during the course of the disease. The design of healthcare and social security systems shapes the country-specific degree of subjective financial distress. Further research should focus on evolving multidisciplinary intervention schemes and multidimensional instruments for subjective financial distress to account for identified risk factors in universal healthcare systems more precisely.

The power of the little ones: Computed and observed aftershock hazard in Central Italy

Seismic hazard in Central Italy due to the 2016–2017 seismic sequence is modeled using a standard probabilistic aftershock seismic hazard model. Two key features of the model are the consideration of time-dependent aftershock occurrence, modeled by stacking Omori decay curves associated with the three largest ( Mw &gt; 5.5) events, and the incorporation of geologic information by modeling the locations of expected seismicity along realistic fault surfaces. The computed seismic hazard at Amatrice indicates higher hazard values compared to those computed using a conventional time-independent hazard analysis. We then compare the computed hazard curves against empirical hazard curves constructed for 12 individual recording stations in terms of peak ground acceleration, each with at least 35 (and up to 231) recordings. At eight sites, the observed exceedances fall within one standard deviation of the expected mean, while at the remaining sites, the observed exceedances fall outside this range indicating a poorer match. The soil sites are among the stations with the poorest match, suggesting that site effects may not be accurately modeled with the current approach.

An observational claims data analysis on the risk of maternal chronic kidney disease after preterm delivery and preeclampsia

Women with complications of pregnancy such as preeclampsia and preterm birth are at risk for adverse long-term outcomes, including an increased future risk of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This observational cohort study aimed to examine the risk of CKD after preterm delivery and preeclampsia in a large obstetric cohort in Germany, taking into account preexisting comorbidities, potential confounders, and the severity of CKD. Statutory claims data of the AOK Baden-Wuerttemberg were used to identify women with singleton live births between 2010 and 2017. Women with preexisting conditions including CKD, ESKD, and kidney replacement therapy (KRT) were excluded. Preterm delivery (< 37 gestational weeks) was the main exposure of interest; preeclampsia was investigated as secondary exposure. The main outcome was a newly recorded diagnosis of CKD in the claims database. Data were analyzed using Cox proportional hazard regression models. The time-dependent occurrence of CKD was analyzed for four strata, i.e., births with (i) neither an exposure of preterm delivery nor an exposure of preeclampsia, (ii) no exposure of preterm delivery but exposure of at least one preeclampsia, (iii) an exposure of at least one preterm delivery but no exposure of preeclampsia, or (iv) joint exposure of preterm delivery and preeclampsia. Risk stratification also included different CKD stages. Adjustments were made for confounding factors, such as maternal age, diabetes, obesity, and dyslipidemia. The cohort consisted of 193,152 women with 257,481 singleton live births. Mean observation time was 5.44 years. In total, there were 16,948 preterm deliveries (6.58%) and 14,448 births with at least one prior diagnosis of preeclampsia (5.61%). With a mean age of 30.51 years, 1,821 women developed any form of CKD. Compared to women with no risk exposure, women with a history of at least one preterm delivery (HR = 1.789) and women with a history of at least one preeclampsia (HR = 1.784) had an increased risk for any subsequent CKD. The highest risk for CKD was found for women with a joint exposure of preterm delivery and preeclampsia (HR = 5.227). These effects were the same in magnitude only for the outcome of mild to moderate CKD, but strongly increased for the outcome of severe CKD (HR = 11.90). Preterm delivery and preeclampsia were identified as independent risk factors for all CKD stages. A joint exposure or preterm birth and preeclampsia was associated with an excessive maternal risk burden for CKD in the first decade after pregnancy. Since consequent follow-up policies have not been defined yet, these results will help guide long-term surveillance for early detection and prevention of kidney disease, especially for women affected by both conditions.

Abstract MP27: Saturated Fat Intake From Dairy Sources Is Associated With Reduced Cardiovascular Risk In Framingham Offspring Study Women

Introduction: While saturated fat (SFA) intake has long been considered as an important risk factor for cardiovascular disease (CVD), some evidence in recent years has called these findings into question. There is limited evidence examining the separate effects of SFAs from different food sources on cardiovascular risk. Objective: The goal of this study was to determine whether higher (vs. lower) intakes of SFA from dairy and non-dairy sources were associated with risk of incident cardiovascular disease. Methods: Data from 1991 adults, ages 30 and older, who were free of CVD at the time of baseline dietary assessment in the prospective Framingham Offspring Study were included in these analyses. Dairy and non-dairy SFA was assessed using 3-day diet records at exams 3 and 5; intakes were adjusted for body weight using the residual method. Subjects were followed from exam 5 to exam 9 for CVD events (median follow-up 16.9 years). Cox proportional hazards models were used to adjust for confounding by sex, age, BMI, physical activity, smoking (pack-years), non-dairy SFA (in dairy SFA models, and vice versa for non-dairy models), and time dependent occurrence of hypertension or use of lipid-lowering medications. Results: Subjects were classified into 3 categories of sex-specific intake of dairy SFA (&lt;9, 9-&lt;13, and ≥13 g/day for men; &lt;6, 6-&lt;9, ≥9 g/day for women) and non-dairy SFA (&lt;15, 15-&lt;18 and ≥18 g/day for men; &lt;12, 12-&lt;15, and ≥15 g/day for women). Women with moderate (vs. low) and high (vs. low) dairy SFA intakes had 56% (95% CI: 0.27-0.71) and 20% (95% CI: 0.56-1.14) lower CVD risks, respectively, while women consuming high (vs. low) non-dairy SFA had 22% (CI: 0.52-1.16) lower risks. Neither dairy-based SFA nor non-dairy SFA intake was associated with CVD occurrence in men. To determine whether the combined effects of SFA from dairy and non-dairy sources were associated with CVD risk, we cross-classified SFA intakes from the two sources (i.e., high/low dairy SFA intake: &lt;9 vs. ≥9 g/day for men, &lt;6 vs ≥6 g/day for women; high/low non-dairy SFA intake: &lt;15 vs. ≥15 g/day for both men &amp; women). Overall, subjects with higher intakes of dairy SFA combined with lower intakes of non-dairy SFA had the lowest risks of CVD (HR:0.73; 95% CI: 0.54-0.98). These effects were stronger in women (HR:0.60; 95% CI: 0.41-0.88), and non-statistically significant in men (HR: 0.88; 95% CI: 0.54-1.43). Women with higher combined intakes of SFA from both dairy and non-dairy sources still had 44% lower risks of CVD. However, higher intakes of SFA from non-dairy sources alone was not associated with CVD risk in either men or women. Conclusions: Saturated fats derived from dairy sources were associated with a reduced risk of incident CVD in women. For both men and women, those who had higher intakes of dairy-derived SFA combined with lower intakes of non-dairy SFA tended to have lower risks of CVD than those with lower intakes of SFA from both sources.

A stochastic model for time series prediction of the number of post-earthquake fire ignitions in buildings based on the ignition record for the 2011 Tohoku Earthquake

This article presents the development of a stochastic model for time series prediction of the number of post-earthquake fire ignitions in buildings for use in post-earthquake fire risk assessment. Two kinds of Poisson regression models with an explanatory variable of JMA instrumental seismic intensity were applied to 126 ignitions affected by ground motion, which were extracted from the ignition record for the 2011 Tohoku Earthquake: (1) a time-dependent occurrence model for the ignitions from electricity-related sources, which is coupled with a statistical model for electrical supply rate after an earthquake, and (2) a time-independent occurrence model for the ignitions from gas-related sources, oil-related sources, and others. In order to verify the models, time series prediction of the number of ignitions in the 2011 Tohoku Earthquake was conducted using Monte Carlo simulation. From the calculated results, we concluded that the models could reasonably explain the occurrence tendency of ignitions in the 2011 Tohoku Earthquake.

1459PD - Efficacy of durvalumab in patients with stage III NSCLC who experience pneumonitis (PACIFIC)

1459PD - Efficacy of durvalumab in patients with stage III NSCLC who experience pneumonitis (PACIFIC)

A Risk Metric for Failure Cause in FMEA under Time-Dependent Failure Occurrence and Detection

A Risk Metric for Failure Cause in FMEA under Time-Dependent Failure Occurrence and Detection

A prospective randomized assessment of quality of life between open and robotic hysterectomy in early endometrial cancer.

There are limited prospective data on the evaluation of quality of life in patients undergoing robotic hysterectomy for endometrial cancer. Our objective was to determine whether post-operative recovery differs between robotic and abdominal hysterectomy. At a Swedish tertiary referral university hospital, 50 women with low-risk endometrial cancer scheduled for surgery between February 2012 and May 2016 were included in a randomized trial. Surgery was performed according to principles for minimal invasive surgery. Anesthesia and peri-operative care followed a standardized enhanced recovery after surgery program in both groups. The EuroQol Group form EQ-5D and the Short Form-36 were used to evaluate patients' health-related quality of life. The Swedish Postoperative Symptoms Questionnaire assessed symptoms pre-operatively, daily for 7 days from the day of surgery, and then weekly until 6 weeks post-operatively. Data were analyzed by means of non-parametric tests and repeated measures ANOVA. To evaluate the time-dependent occurrence of complications, Kaplan-Meier survival and Cox proportional-hazard models were used. A total of 50 women were enrolled in the study (25 robotic and 25 abdominal hysterectomy). Median age (68 years vs 67 years), estimated blood loss (50 mL vs 50 mL), length of hospital stay de facto (53 hours vs 51 hours), and time to meet discharge criteria (36 hours vs 36 hours) in the robotic and abdominal groups, respectively, did not differ significantly (p>0.05) Women in the robotic hysterectomy group recovered significantly faster (p=0.01) in the EQ-5D health index, and reached their pre-operative level after approximately 3 weeks, nearly 2 weeks earlier than the abdominal group. Differences regarding improvement in health-related quality of life (Short Form-36) were statistically significant in general health and social functioning only, and were in favor of robotic hysterectomy. Consumption of analgesics, pain intensity, and symptom sum score post-operatively were equal. Occurrence of complications was an independent risk factor and influenced significantly the EQ-5D health index, length of hospital stay, pain intensity, opioid consumption, and symptom sum score adversely. Robotic hysterectomy in the setting of an enhanced recovery after surgery program led to faster recovery in health-related quality of life compared with abdominal hysterectomy.

Thrombus aspiration in patients with ST-elevation myocardial infarction presenting late after symptom onset: long-term clinical outcome of a randomized trial.

In the largest randomized trial so far, thrombus aspiration failed to reduce the primary endpoint of microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI) presenting late after symptom onset. Long-term clinical outcome data of this trial have not been reported yet. A total of 144 patients with STEMI presenting ≥ 12 and ≤ 48h after symptom onset were randomized to primary percutaneous coronary intervention (PCI) with or without manual thrombus aspiration in a 1:1 fashion. The primary efficacy endpoint was the extent of MVO assessed by cardiac magnetic resonance imaging and showed no significant difference between groups. Long-term clinical follow-up was performed at 4years. Overall mortality at 4years reached 18%. There was no significant difference between groups with respect to mortality and major adverse cardiac events defined as the composite of death, myocardial reinfarction and target vessel revascularization. In a multivariate Cox regression model glomerular filtration rate on admission, left ventricular ejection fraction, and cardiogenic shock were independently associated with time-dependent occurrence of death. Routine thrombus aspiration in STEMI patients presenting late after symptom onset showed no significant difference with respect to long-term clinical endpoints compared to conventional PCI only.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

The time dependency of renal allograft histology.

Much of the complexity of the histological appearance of kidney transplant biopsies depends on the time at which the biopsies are obtained. It is well established that many elementary histological lesions and diagnoses have a time-dependent occurrence. While some "active" inflammatory lesions are noted primarily early after transplantation, other lesions are "chronic" and accumulate over time post-transplant, sometimes closely related to the prior active inflammatory lesions. With time after transplantation, the complexity of histology increases, by the co-occurrence of chronic damage and specific diseases. This leads to difficulties in clinical interpretation of the histological picture. We discuss the time-dependent prevalence of active and chronic lesions in kidney allograft biopsies and their associations with outcome. We also elaborate on the importance of time post-transplant in the interpretation of complex histological lesions or mixed diagnoses and illustrate that further research is necessary to evaluate whether time post-transplant is important for prognostication of graft injury processes. Adding a multidimensional prognostic layer to the current diagnostic Banff classification, including graft functional characteristics and time after transplantation, could become an interesting aid in the interpretation of complex histological lesions and mixed diagnoses, and in therapeutic decision-making.

Time-dependent Occurrence Rate of Electromagnetic Cyclotron Waves in the Solar Wind: Evidence for the Effect of Alpha Particles?

Abstract Previous studies revealed that electromagnetic cyclotron waves (ECWs) near the proton cyclotron frequency exist widely in the solar wind, and the majority of ECWs are left-handed (LH) polarized waves. Using the magnetic field data from the STEREO mission, this Letter carries out a survey of ECWs over a long period of 7 years and calculates the occurrence rates of ECWs with different polarization senses. Results show that the occurrence rate is nearly a constant for the ECWs with right-handed polarization, but it varies significantly for the ECWs with LH polarization. Further investigation of plasma conditions reveals that the LH ECWs take place preferentially in a plasma characterized by higher temperature, lower density, and larger velocity. Some considerable correlations between the occurrence rate of LH ECWs and the properties of ambient plasmas are discussed. The present research may provide evidence for the effect of alpha particles on the generation of ECWs.

Impact of multivessel coronary artery disease on reperfusion success in patients with ST-elevation myocardial infarction: A substudy of the AIDA STEMI trial.

A significant portion of patients with ST-elevation myocardial infarction (STEMI) display multivessel coronary artery disease. However, data on the association of multivessel coronary artery disease and reperfusion success are scarce. The aim of the current study was to analyse the impact of multivessel coronary artery disease on myocardial salvage assessed by cardiac magnetic resonance imaging in a large unselected cohort of STEMI patients. STEMI patients ( n=738) included in the AIDA STEMI trial underwent primary percutaneous coronary intervention within 12 hours after symptom onset. Cardiac magnetic resonance imaging was performed 3 days after the index event (interquartile range (IQR) 2-4). The severity of coronary artery disease was graded as single-vessel disease compared to multivessel disease. The primary endpoint was defined as a composite of death, non-fatal myocardial re-infarction and congestive heart failure (major adverse cardiac events) at 12 months. Multivessel coronary artery disease was present in 46.3% ( n=342) of all patients. Patients with multivessel coronary artery disease were older and more often had diabetes in comparison to those with single-vessel disease ( P<0.001 and P=0.005). Angiographic and electrocardiographic reperfusion success defined as Thrombolysis in Myocardial Infarction flow III post-percutaneous coronary intervention and ST-segment resolution ⩾70% were similar between both groups ( P=0.48 and P=0.21). Patients with multivessel disease displayed no significant difference with respect to myocardial salvage index (49.8 (IQR 31.4-71.6) versus 52.7 (IQR 35.1-67.1), P=0.81) in comparison to patients with single-vessel disease. The presence of multivessel coronary artery disease was identified as an independent predictor for the time-dependent occurrence of major adverse cardiac events (hazard ratio 3.25, 95% confidence interval 1.53-6.91, P=0.002). Although multivessel coronary artery disease is not associated with impaired reperfusion success assessed by cardiac magnetic resonance imaging, patients with multivessel disease are at a high risk of adverse clinical outcomes. Clinicaltrials.gov NCT00712101.

Abstract 13850: Severity Assessment of Coronary Artery Aneurysm by Z-score of the Internal Diameter in Kawasaki Disease

Introduction: The severity of coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) has been recently classified according to the z-score. However, it is not known whether this classification can predict coronary events such as stenosis, obstruction, and thrombosis. Methods: In this multicenter retrospective study, data on height, weight, CAA diameter measured by echocardiography in the acute phase, and the clinical course in KD patients 18 years of age or younger who received a coronary angiography between 1992 and 2011 were collected. Time-dependent occurrence of coronary events was analyzed by Kaplan-Meier method according to small (z-score, &lt; 5.0), medium (≥ 5.0 to &lt; 10.0), and large (≥ 10.0) CAA using a 5 increment scale scheduled to be included in the new American Heart Association criteria. Cox regression analysis was used to identify risk factors for coronary events. The occurrence rate of major cardiac events such as angina pectoris, myocardial infarction, and cardiac death was also analyzed. Results: Data were analyzed for 1,002 patients from 44 institutions. Both the body surface area and CAA diameters were available in 741 cases for the right coronary artery (RCA) and 609 cases for the left anterior descending artery (LAD). Coronary events occurred in 83 (11.2%) of the RCA group and 57 (9.4%) of the LAD group, while major events occurred in 30 cases (3.0%). The 10-year event-free survival rate for coronary events for small, medium, and large aneurysms was 100, 95.5, and 64.9% in the RCA group, and 100, 94.4, and 63.5% for aneurysms in the LAD group, respectively. The rate of major cardiac events was 98.5, 98.1, and 87.6% for the RCA group, and 100, 97.5, and 86.8% for the LAD group, respectively. Cox regression analyses showed that the z-score of the CAA diameter was an independent risk factor for coronary events for the RCA [large versus medium aneurysm; hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.5 to 5.3, p = 0.002] and the LAD [HR 3.2, 95% CI 1.6 to 6.5, p = 0.015] groups. Conclusions: The severity assessment of CAA using the 5-increment z-score for coronary arterial diameter can predict the time-dependent occurrence of coronary events in patients with KD.

Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz.

Adverse drug reactions associated with efavirenz (EFV) therapy are poorly described beyond the first year of treatment. We aimed to describe the incidence and predictors of EFV-related adverse drug reactions (ADRs) in a cohort of adult Nigerian HIV-infected patients on antiretroviral therapy (ART). This retrospective cohort study utilized clinical data of HIV-1 infected adults (aged ≥15 years), commenced on efavirenz containing-regimen between January 2004 and December 2011. The time-dependent occurrence of clinical adverse events as defined by the World Health Organization was analyzed by Cox regression analysis. A total of 2920 patients with baseline median (IQR) age of 39 (33-46) years, largely made up of men (78%) were included in the study. During 8834 person-years of follow up, 358 adverse drug events were reported; the incidence rate was 40.3 ADRs per 1000 person-years of treatment. Lipodystrophy and neuropsychiatric disorders were the most common ADRs with incidences of 63 and 30 per 1000 patients respectively. About one-third of the neuropsychiatric adverse events were within 12 months of commencement of ART. The risk of neuropsychiatric ADRs was independently predicted for women [adjusted hazard ratio (aHR) 9.05; 95% CI: 5.18-15.82], those aged <40 years (aHR 2.59; 95% CI: 1.50-4.45), advanced HIV disease (WHO stage 3 or 4) [aHR 2.26; 95% CI: 1.37-3.72], and zidovudine [aHR 2.21; 95% CI: 1.27-3.83] or stavudine [aHR 4.22; 95% CI: 1.99-8.92] containing regimen compared to tenofovir. Neuropsychiatric adverse drug events associated with efavirenz-based ART had both early and late onset in our clinical cohort of patients on chronic EFV therapy. Continuous neuropsychiatric assessment for improved detection and management of neuropsychiatric ADRs is recommended in resource-limited settings where the use of efavirenz-based regimens has been scaled up.