POS0325 RADIOMIC BIOMARKER OF PULMONARY VASCULAR RELATED STRUCTURES PREDICTS MORTALITY IN SYSTEMIC SCLEROSIS

Background:Quantitative computed tomography (QCT) extracts features from high-resolution CT scans and quantifies lung parenchymal and vascular abnormalities which may not be discernable by qualitative review. The threshold values of individual parenchymal abnormalities and vascular features measured by QCT methods which associate with mortality in systemic sclerosis (SSc) are currently unknown.Objectives:To determine whether QCT measures, specifically pulmonary parenchymal abnormalities and pulmonary vascular related structures (PVRS), can predict mortality in SSc and to determine the optimal quantitative thresholds for those parameters.Methods:A total of 133 subjects (76% women) meeting 2013 ACR/EULAR classification criteria for SSc with a baseline CT within 3 years of diagnosis were retrospectively identified for inclusion. CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) was used to quantitatively measure volume of ground glass opacities (GGO), reticular densities, and honeycombing (HC). Total interstitial lung disease (ILD) was the summation of these features. PVRS was also quantified using CALIPER. Values for each feature were expressed as a percentage of total lung volume. Cox models evaluated the hazard ratio (HR) for mortality for each parameter adjusting for age at SSc diagnosis, sex, diffuse SSc subtype, and history of smoking. The optimal thresholds for mortality prediction for each parameter were determined using consensus between 4 methods: Contal and O’Quigley Method, Cox Model Hazard Ratio, Cox Model Wald P-value, and False Discovery Rate. The c-statistic was used to assess each models’ ability to predict mortality.Results:Mean ±SD for age at SSc diagnosis was 61 ± 13 years and length of follow-up was 4.7 ± 3.0 years. There were 32 deaths (24%). A Cox model including age (HR 1.05, 95% CI: 1.01-1.09), female sex (HR 0.49, 95% CI: 0.22-1.08), diffuse SSc subtype (HR 1.50, 95% CI: 0.69-3.30), and history of smoking (HR 2.09, 95% CI: 0.97-4.53) (Model 1) significantly predicted mortality (C-statistic 0.72, 95% CI: 0.63-0.81). Adjusting for Model 1, reticular densities% (HR 1.19, 95% CI: 1.05-1.35), total ILD% (HR 1.02, 95% CI: 1.00-1.03), and PVRS% (HR 1.19, 95% CI: 1.05-1.35) were associated with mortality on univariable analyses; GGO% (HR 1.01, 95% CI: 0.98-1.04) was not significantly associated with mortality. The optimal thresholds for mortality prediction were then determined and were as follows: GGO=20%, reticular densities=8%, total ILD=20%, and PVRS=5%. While the risk of mortality was significantly increased in subjects with GGO ≥20% (HR 2.70, 95% CI: 1.21-6.05), reticular densities ≥8% (HR 4.64, 95% CI: 1.68-12.81), and total ILD ≥20% (2.59, 95% CI: 1.12-5.99), these baseline thresholds did not improve upon mortality prediction when added individually to Model 1 (C-statistic 0.73 for each). PVRS ≥5%, which had an over six-fold increase in mortality (HR 6.42, 95% CI: 2.60-15.88), did improve mortality prediction when added to Model 1 (C-statistic 0.78, 95% CI: 0.70-0.86).Conclusion:PVRS strongly associates with early mortality in patients with SSc and represents a novel radiomic biomarker that provides prognostic information on mortality beyond pulmonary parenchymal abnormalities. CALIPER derived PVRS quantifies CT data through a function that defines connected tubular branching structures. This extracts pulmonary arteries and veins from the adjacent parenchyma but could potentially also include regions of adjoining of fibrosis.1 Larger studies examining the association between PVRS and progression of cardiopulmonary disease are warranted.References:[1]Jacob J, Bartholmai BJ, Rajagopalan S, et al. Predicting Outcomes in Idiopathic Pulmonary Fibrosis Using Automated Computed Tomographic Analysis. Am J Respir Crit Care Med 2018;198:767-76.Acknowledgements:This project was supported by the Mayo Clinic Margaret Harvey Schering Clinician Career Development Award.Disclosure of Interests:Alicia Hinze: None declared, Yasser Radwan: None declared, Mamoun Elnagar: None declared, Reto Kurmann: None declared, Shreyasee Amin: None declared, Robert Vassallo Grant/research support from: Pfizer, Bristol Myers Squibb, Sun Pharma, Cynthia S. Crowson: None declared, Brian Bartholmai Consultant of: AstraZenica, Boehringer Ingelheim, Promedior LLC (all <$5,000 annually)

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Acquisition of Cytogenetic Abnormalities (CA) Is a Very Poor Prognostic Feature in Patients (pts) with Low and Intermediate-1 (int-1) Risk Myelodysplastic Syndromes (MDS),

Blood ◽

10.1182/blood.v118.21.3802.3802 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3802-3802

Author(s):

Elias Jabbour ◽

Hagop M. Kantarjian ◽

Xuemei Wang ◽

Lynne V. Abruzzo ◽

A Megan Cornelison ◽

...

Keyword(s):

Lower Risk ◽

Research Funding ◽

Regression Models ◽

Cox Model ◽

Time Dependent ◽

P Value ◽

Increased Risk ◽

History Of ◽

Previously Treated ◽

The Impact

Abstract Abstract 3802 Background and Aim: The impact of the CA on prognosis and transformation into acute myeloid leukemia among pts with low and int-1 risk MDS is not known. The aims of the study were to assess the impact of CA on the natural history of pts with lower risk MDS and to identify factors associated with its development. Methods: We reviewed 721 pts clinical records of low and intermediate risk MDS pts from 2000–2010 and conducted a retrospective analysis of all pts with at least two consecutive cytogenetic analysis (365 patients, 51%). The acquisition of CA was defined by structural change or gain in at least 2 metaphases and loss in 3 metaphases, or otherwise confirmed by FISH. Cox proportional hazards regression models were fit to assess the association between transformation-free survival (TFS) or overall survival (OS) and pt characteristics. The acquisition of CA was fitted in the Cox model as a time-dependent covariate. The association between the acquisition of CA and pt characteristics was assessed through univariate and multiple logistic regression models. Results: CA was detected in 107 pts (29%) after a median follow-up of 34 months (mos). CA was observed in a median number of 4 metaphases (range, 2–30). At diagnosis, 21% and 79% of pts who acquired CA were low-and int-1risk MDS; 50% were diploid, 22% harbored chromosome 5 /7 abnormalities. At the time of acquisition of CA, the median percentage of bone marrow blasts was 4% (range, 0% to 89%), the median WBC, hemoglobin and platelets were 3.1 × 109/L, 9.5 g/dL, and 65 × 109/L, respectively; pts were low, int-1, int-2, and high-risk MDS in 3%, 42%, 26%, 29%, respectively. The median TFS and OS were 31 (95% CI: 27– 37) and 34 (95% CI: 30 – 44) mos respectively. Assessing CA as time-dependent covariate, patients with CA had a worse TFS and OS, with a median TFS and OS of 16 and 18 mos compared to 56 and 60 mos, respectively in pts without CA. Based on the multivariable Cox model and after adjusting for effects of all other covariates, pts who had acquired CA had an increased risk of transformation (HR=1.46; p-value = 0.01) or death (HR=1.50; p-value = 0.01). By multivariate analysis, female pts with prior chemotherapy had an increased risk of developing CA (OR= 5.26; p-value <0.0001). 96 pts had history of previous malignancy treated with chemotherapy +/− radiation therapy. Of those, 34 (35%) patients acquired CA. Median time from previous chemotherapy to the acquisition of CA was 61 mos (range, 11 to 180). Pts previously treated who did not acquire CA had similar outcomes to those who had never been treated and did not develop CA, while those who did develop CA whether they were previously treated or not had worse TFS and OS. Conclusion: CA occurs at a rate of 29% of pts with lower risk MDS, more common among pts with previously treated malignancy, and has a significant impact on TFS and OS, possibly reflecting genomic instability in the natural history of MDS. Disclosures: Cortes: BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

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The natural history of progressive fibrosing interstitial lung diseases

European Respiratory Journal ◽

10.1183/13993003.00085-2020 ◽

2020 ◽

Vol 55 (6) ◽

pp. 2000085 ◽

Cited By ~ 9

Author(s):

Kevin K. Brown ◽

Fernando J. Martinez ◽

Simon L.F. Walsh ◽

Victor J. Thannickal ◽

Antje Prasse ◽

...

Keyword(s):

Natural History ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Hazard Ratio ◽

P Value ◽

Risk Of Death ◽

Increased Risk ◽

History Of ◽

Relative Decline ◽

Rate Of Decline

We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs).Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year−1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials.The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (−192.9 mL·year−1 and −221.0 mL·year−1, respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95).These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.

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POS0322 CORRELATION BETWEEN QUANTITATIVE COMPUTED TOMOGRAPHY AND DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4261 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 388.2-388

Author(s):

D. Sambataro ◽

M. Orlandi ◽

M. Colaci ◽

L. Malatino ◽

G. Sambataro ◽

...

Keyword(s):

Computed Tomography ◽

Systemic Sclerosis ◽

Standard Deviation ◽

Disease Activity ◽

Activity Index ◽

Pulmonary Function Tests ◽

Quantitative Computed Tomography ◽

P Value ◽

Operating Characteristics ◽

Parenchymal Lung

Background:High Resolution Computed Tomography (HRCT) is the gold standard to evaluate Interstitial Lung Diseases (ILDs) extent and severity. Quantitative Computed Tomography (QCT) is a promising tool as it provides an operator-independent assessment of ILD extent. Even if there are emerging data on QCT in Systemic Sclerosis (SSc), its correlation with disease activity (DA) has not been yet studied.Objectives:To evaluate the correlation between QCT score and DA in an Italian cohort of SSc patients.Methods:A multicentric, observational study was conducted in three Italian rheumatological centers.Adult SSc patients classified according to the ACR/EULAR 2013 criteria [1] were assessed with pulmonary function tests, HRCT and for DA. CT images were analyzed quantitatively with the densitometric radiomic data obtained through a free open software – Mean lung attenuation (MLA), Standard Deviation (SD), Kurtosis, Skewness and Lung volume. DA assessment was conducted according to EUSTAR index [2]: a score ≥2.5 was considered indicative of high disease activity.Age below 18 and pregnancy were considered exclusion criteria. We used Student’s T test to evaluate the means of the parameters, Pearson’s r test for correlations, receiver operating characteristics curve to define the cutoff values of the significant details, and linear regression with collinearity test to define the role of the details. P value <0.05 was considered statistically significant.Results:Sixty patients were enrolled (male 8, female 52), with mean age 53.2 years (SD 15.6) and mean disease duration 5.3 years (SD 4.2). QCT indexes distribution was different in high DA vs low DA SSc patients. In particular mean lung attenuation (MLA, -834.7 vs -812.1, p =0.03), standard deviation (95.9 vs 102, p =0.03), skewness (2.2 vs 1.7, P =0.006) and kurtosis (5.5 vs 3.3, p =0.009) of the parenchymal lung and skewness (3.1 vs 2.8, p =0.03) of the whole lung were statistically different. DA correlates with MLA (r =0.28, p =0.003), standard deviation (r =0.21, p =0.02), skewness (r =-0.32, p =0.001) and kurtosis (r =-0.29, p =0.001) of the parenchymal lung and MLA (r =0.25, p =0.006), skewness (R =-0.27, p =0.003), kurtosis (r =-0.21, P =0.02) of the whole lung. The skewness of the parenchymal lung was the QCT index with the best performance in identifying high DA SSc patients (cutoff value ≤1.85; area under the curve 0.74, p =0.005; sensitivity 79.5%, specificity 68.7% accuracy 76.6%).Conclusion:To our knowledge, this is the first study which correlate the QCT score with DA in SSc patients. Our results suggest that QCT can identify SSc patients with high DA score. This could open a scenario of new applications as an operator-independent contribution in DA scores with a potential role in clinical practice. Further studies are needed to confirm the data and to better identify the most suitable parameters for the purpose.References:[1]Van den Hoogen F, et al. 2013 classification criteria for Systemic Sclerosis: and American college of rheumatology / European league against rheumatism collaborative initiative. Ann Rheum Dis 2013;72:1747-1755.[2]Valentini G, et al. The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index. Ann Rheum Dis 2017;76:270-276.Disclosure of Interests:None declared

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Mutations in Histone Modulators Are Associated with Prolonged Survival during Azacitidine Therapy

Blood ◽

10.1182/blood.v126.23.2839.2839 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2839-2839

Author(s):

Magnus Tobiasson ◽

Donal McLornan ◽

Mohsen Karimi ◽

Marios Dimitriou ◽

Monika Jansson ◽

...

Keyword(s):

Disease Duration ◽

Response Rate ◽

Cox Regression ◽

Cox Model ◽

Hazard Ratio ◽

Prolonged Survival ◽

Forest Plot ◽

P Value ◽

Kaplan Meier ◽

Pre Treatment

Abstract Early therapeutic decision-making is crucial in patients with higher-risk MDS where median survival is only around one year. Azacitidine prolongs survival for these patients (Fenaux et al, Lancet Oncology 2009) but clinically relevant biomarkers remain to be identified. We evaluated retrospectively, the impact of clinical parameters and mutational profiles in 134 consecutive patients treated with a median number of 7 cycles of Azacitidine (range 1-45), in accordance to European guidelines. The vast majority (n=114) had higher-risk disease i.e. MDS with IPSS int-2 or high, AML with multilinear dysplasia and 20-30% blasts or CMML-II. We combined an initial cohort from Karolinska University Hospital (n=89) with a validating cohort from King's College Hospital, London (n=45). Studied endpoints were response, as defined by the IWG criteria, and survival. Since prolonged survival is the main goal for this cohort of patients, we believe that survival is the most relevant endpoint, supported by the fact that even non-responding patients have a survival benefit from Azacitidine (Gore et al, Haematologica, 2013). While neither clinical parameters nor mutations had a significant impact on response rate, both karyotype and mutational profile were strongly associated with survival from the start of treatment, see Table 1 and Figure 1-2. IPSS high-risk cytogenetics was negatively associated with survival (median 20 vs 10 months; p<0.001), whereas mutations in histone modulators (ASXL1, EZH2, MLL) were associated with prolonged survival (22 vs 12 months, p=0.001). This positive association was present in both cohorts and remained highly significant in the multivariate cox model. Importantly, patients with mutations in histone modulators lacking high-risk cytogenetics showed a survival of 29 months (response rate 73%) compared to 10 months (response rate 49%) in patients with the opposite pattern, see Figure 3. While TP53 was negatively associated with survival in the univariate analysis, neither RUNX1-mutations nor the number of mutations, previously reported as negative prognostic markers, appeared to influence survival in this cohort. In contrast, disease duration and cellularity showed a weak negative correlation with survival. We propose a model combining histone modulator mutational screening with cytogenetics in the clinical decision-making process for higher-risk MDS eligible for treatment with Azacitidine. Table 1. Variables associated with survival. Univariate analyses used the log-rank test. The cox model included all listed variables except response rate in a multivariate analyses. Estimated median survival (months) Univariate p-value Cox regression p-value Hazard ratio (95% CI) Response rate: CR / mCR vs PR/HI vs SD/PD 20 vs 20 vs 10 <0.001 IPSS cytogenetic risk group: Favorable vs Int vs Adverse 20 vs 20 vs 10 <0.001 <0.001* 3.00 (1.9-4.7) Disease duration ≥ 4 months: Yes vs No 14 vs 17 0.44 0.05** 1.01 (1.00-1.02) Marrow blasts ≥ 11%: Yes vs No 14 vs 14 0.7 Cellularity ≥ 70%: Yes vs No 14 vs 20 0.2 0.02 1.013 (1.002-1.023)** ANC ≥ 1.3: Yes vs No 14 vs 17 0.32 Platelets ≥ 60: Yes vs No 17 vs 12 0.07 Transfusion dependent: Yes vs No 13 vs 17 0.43 Therapy related: Yes vs No 17 vs 14 0.44 Number of mutations: 0 vs 1 vs ≥ 2 17 vs 12 vs 17 0.64 Epigenetic mutation: Yes vs No 19 vs 12 0.03 DNA methylation mutation: Yes vs No 14 vs 14 0.64 Histone modulator mutation: Yes vs No 22 vs 12 0.001 0.007 0.499 (0.3-0.83) Splicing factor mutation: Yes vs No 13 vs 17 0.31 ASXL1 mutation: Yes vs No 29 vs 12 0.03 TET2 mutation: Yes vs No 13 vs 16 0.45 EZH2 mutation: Yes vs No 20 vs 14 0.37 SF3B1 mutation: Yes vs No 13 vs 16 0.35 RUNX1 mutation: Yes vs No 17 vs 14 0.76 SRSF2 mutation: Yes vs No 20 vs 14 0.5 TP53 mutation: Yes vs No 9 vs 17 <0.001 *Comparing adverse cytogenetics vs the other groups. ** Disease duration, marrow blasts, cellularity, ANC and TPK were analyzed as a continuous variable in the cox model Figure 1. Kaplan-Meier estimated survival stratified for response and pre-treatment parameters Figure 1. Kaplan-Meier estimated survival stratified for response and pre-treatment parameters Figure 2. Forest plot indicating hazard ratio including confidence interval for all pre-treatment variables. The hazard ratios were retrieved using cox univariate regression models for each variable analyzed separately. Figure 2. Forest plot indicating hazard ratio including confidence interval for all pre-treatment variables. The hazard ratios were retrieved using cox univariate regression models for each variable analyzed separately. Figure 3. Kaplan-Meier estimated survival stratified for the two dominant predictors in the cox regression model: Adverse cytogenetics and histone modulator mutations Figure 3. Kaplan-Meier estimated survival stratified for the two dominant predictors in the cox regression model: Adverse cytogenetics and histone modulator mutations Disclosures McLornan: Novartis: Research Funding, Speakers Bureau. Jädersten:Celgene: Other: speakers fee. Kulasekararaj:Alexion: Consultancy. Mufti:Celgene: Consultancy, Other: Speakers fee. Hellström-Lindberg:Celgene Corporation: Research Funding.

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Penanganan Ties Event dalam Regresi Cox Proportional Hazard Menggunakan Metode Breslow (Kasus: Pasien Rawat Inap DBD di RSAL Jala Ammari Makassar)

VARIANSI: Journal of Statistics and Its application on Teaching and Research ◽

10.35580/variansiunm12897 ◽

2020 ◽

Vol 2 (1) ◽

pp. 13

Author(s):

Herawati Hafid ◽

Muhammad Nadjib Bustan ◽

Muhammad Kasim Aidid

Keyword(s):

Survival Analysis ◽

Dengue Hemorrhagic Fever ◽

Recovery Rate ◽

Cox Model ◽

Hemorrhagic Fever ◽

Hazard Ratio ◽

Partial Likelihood ◽

P Value ◽

Proportional Hazard ◽

Cox Proportional Hazard

Abstrak Analisis Survival adalah prosedur statistika yang digunakan untuk menganalisis data dimana peubah yang diperhatikan adalah waktu sampai terjadinya suatu event. Waktu dapat dinyatakan dalam hitungan hari, minggu, bulan dan tahun. Salah satu tujuan dari analisis survival adalah untuk mengetahui hubungan antara waktu kejadian peubah bebas yang terukur pada saat dilakukan penelitian. Metode yang sering digunakan dalam analisis survival khususnya data kesehatan adalah Regresi Cox Proportional Hazard (PH) karena distribusinya tidak tergantung pada asumsi waktu kejadian. Dalam suatu data seperti data pasien penderita penyakit Demam Berdarah Dengue (DBD) ditemukan adanya data kejadian bersama (ties event) yang berpengaruh pada pembentukan himpunan risikonya pada bagian estimasi parameter model cox,pada kasus kejadian bersama (ties event) dilakukan modifikasi pada partial likelihood untuk mengetahui faktor-faktor yang mempengaruhi laju kesembuhan pasien penderita penyakit DBD. Adapun hasil analisisnya, diperoleh faktor yang paling berpengaruh terhadap laju kesembuhan penyakit DBD yakni leukosit dengan p-value =0,097< α 0,05, dan nilai hazard ratio sebesar 1,1024 serta faktor yang kedua yaitu hematokrit dengan p-value =0,0141< α 0,05, dan nilai hazard ratio sebesar 1,595. Kata Kunci: Analisis Survival, Regresi Cox PH, Ties Event, Metode Breslow, Demam Berdarah Dengue (DBD). Abstract Survival analysis is a statistical procedure that is used to analyze data where the variables considered are the time until the occurrence of an event. Time can be expressed in days, weeks, months and years. One of the objectives of survival analysis is to find out the relationship between the time of occurrence of independent variables measured at the time of the study. The method often used in survival analysis, especially health data, is Cox Proportional Hazard (PH) Regression because its distribution does not depend on the assumption of the time of the event. In a data such as data on patients with Dengue Hemorrhagic Fever (DHF) data, there were ties event data that influenced the formation of risk sets in the cox model parameter estimation section, in the case of ties event modifications were made to the partial likelihood for know the factors that influence the recovery rate of patients with DHF. As for the results of the analysis, the factors that most influence the recovery rate of leucocyte dengue fever with p-value = 0,097 < α = 0,05 and the hazard ratio of 1.1024 and the second factor is the hematocrit with p-value = 0,0141 < α = 0,05 and the hazard ratio valueamounting to 1,595. Keywords: Survival Analysis, Cox PH Regression, Ties Event, Breslow Method, Dengue Hemorrhagic Fever (DHF).

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Temporal trends in utilization of transcatheter aortic valve implantation and patient characteristics – a nationwide cohort study

European Heart Journal ◽

10.1093/ehjci/ehaa946.2618 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.E Strange ◽

C Sindet-Pedersen ◽

G Gislason ◽

C Torp-Pedersen ◽

E.L Fosboel ◽

...

Keyword(s):

Aortic Valve ◽

Transcatheter Aortic Valve Implantation ◽

Temporal Trends ◽

Patient Characteristics ◽

P Value ◽

Transcatheter Aortic Valve ◽

History Of ◽

Aortic Valve Implantation ◽

Valve Implantation ◽

First Time

Abstract Introduction In recent years, there has been a surge in the utilization of transcatheter aortic valve implantation (TAVI) for the treatment of severe symptomatic aortic stenosis. Randomized controlled trials have compared TAVI to surgical aortic valve replacement (SAVR) in patients at high-, intermediate-, and low perioperative risk. As TAVI continues to be utilized in patients with lower risk profiles, it is important to investigate the temporal trends in “real-world” patients undergoing TAVI. Purpose To investigate temporal trends in the utilization of TAVI and examine changes in patient characteristics of patients undergoing first-time TAVI. Methods Using complete Danish nationwide registries, we included all patients undergoing first-time TAVI between 2008 and 2017. To compare patient characteristics, the study population was stratified according to calendar year in the following groups: 2008–2009, 2010–2011, 2012–2013, 2014–2015, and 2016–2017. Results We identified 3,534 patients undergoing first-time TAVI. In 2008–2009, 180 patients underwent first-time TAVI compared with 1,417 patients in 2016–2017, resulting in a 687% increase in TAVI procedures performed. During the study period, the median age remained stable (2008–2009: Median age 82 year [25th–75th percentile: 78–85] vs. 2016–2017: Median age 81 years [25th–75th percentile: 76–85]; P-value: 0.06). The proportion of men undergoing first-time TAVI increased over the years (2008–2009: 49.4% vs 2016–2017: 54.9%; P-value for trend: <0.05), also the proportion with diabetes increased (2008–2009: 12.2% vs. 2016–2017: 19.3%; P-value for trend: <0.05). The proportion of patients with a history of stroke decreased over the years (2008–2009: 13.9% vs. 2016–2017: 12.1%; P-value for trend: <0.05). The same trend was seen in patients with a history of myocardial infarction (2008–2009: 24.4% vs. 2016–2017: 11.9%; P-value for trend: <0.05), ischaemic heart disease (2008–2009: 71.7% vs. 2016–2017: 29.4%; P-value for trend: <0.05), and heart failure (2008–2009: 45.6% vs. 2016–2017: 29.4%; P-value for trend: <0.05). Conclusions In this nationwide study, there was a marked increase in the utilization of TAVI in the years 2008–2017. Patients undergoing first-time TAVI had a decreasing comorbidity burden, while the age of the patients at first-time TAVI remained stable. Funding Acknowledgement Type of funding source: None

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An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events

Journal of Personalized Medicine ◽

10.3390/jpm11030178 ◽

2021 ◽

Vol 11 (3) ◽

pp. 178

Author(s):

Noah R. Delapaz ◽

William K. Hor ◽

Michael Gilbert ◽

Andrew D. La ◽

Feiran Liang ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Previous History ◽

Current Treatment ◽

Careful Consideration ◽

P Value ◽

Post Traumatic Stress ◽

Increased Risk ◽

History Of ◽

Almost All

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

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Clinical significance of Q waves in ischemic cardiomyopathy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.340 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

E Rodenas Alesina ◽

P Jordan ◽

L Herrador ◽

C Espinet-Coll ◽

N Pizzi ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Cox Model ◽

Cardiovascular Death ◽

P Value ◽

Heart Failure Hospitalization ◽

Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF < 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF <40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between >10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if >10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR < 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 <0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia > 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211034074 ◽

2021 ◽

pp. 239719832110340

Author(s):

Yasser A Radwan ◽

Reto D Kurmann ◽

Avneek S Sandhu ◽

Edward A El-Am ◽

Cynthia S Crowson ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Confidence Interval ◽

Cumulative Incidence ◽

Disease Onset ◽

Population Based ◽

Hazard Ratio ◽

Conduction Disorders ◽

Increased Risk

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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