Investigating the Impact of Early Valve Surgery on Survival in Staphylococcus aureus Infective Endocarditis Using a Marginal Structural Model Approach: Results of a Large, Prospectively Evaluated Cohort

2018 ◽  
Vol 69 (3) ◽  
pp. 487-494 ◽  
Author(s):  
Siegbert Rieg ◽  
Maja von Cube ◽  
Achim J Kaasch ◽  
Bastian Bonaventura ◽  
Wolfgang Bothe ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Trials ◽  
Survival Benefit ◽  
Structural Model ◽  
Cox Regression ◽  
Cox Model ◽  
Valve Surgery ◽  
Time Dependent ◽  
Marginal Structural Model ◽  
The Impact

Abstract Background The impact of valve surgery on outcomes of Staphylococcus aureus infective endocarditis (SAIE) remains controversial. We tested the hypothesis that early valve surgery (EVS) improves survival by using a novel approach that allows for inclusion of major confounders in a time-dependent way. Methods EVS was defined as valve surgery within 60 days. Univariable and multivariable Cox regression analyses were performed. To account for treatment selection bias, we additionally used a weighted Cox model (marginal structural model) that accounts for time-dynamic imbalances between treatment groups. To address survivor bias, EVS was included as a time-dependent variable. Follow-up of patients was 1 year. Results Two hundred and three patients were included in the analysis; 50 underwent EVS. All-cause mortality at day 30 was 26%. In the conventional multivariable Cox regression model, the effect of EVS on the death hazard was 0.85 (95% confidence interval [CI], .47–1.52). Using the weighted Cox model, the death hazard rate (HR) of EVS was 0.71 (95% CI, .34–1.49). In subgroup analyses, no survival benefit was observed in patients with septic shock (HR, 0.80 [CI, .26–2.46]), in NVIE (HR, 0.76 [CI, .33–1.71]) or PVIE (HR, 1.02 [CI, .29–3.54]), or in patients with EVS within 14 days (HR, 0.97 [CI, .46–2.07]). Conclusions Using both a conventional Cox regression model and a weighted Cox model, we did not find a survival benefit for patients who underwent EVS in our cohort. Until results of randomized controlled trials are available, EVS in SAIE should be based on individualized decisions of an experienced multidisciplinary team. Clinical Trials Registration German Clinical Trials registry (DRKS00005045).

The impact of statin therapy after surgical or endovascular treatment of cerebral aneurysms

2020 ◽  
Vol 133 (1) ◽  
pp. 182-189
Author(s):  
Tae-Jin Song ◽  
Seung-Hun Oh ◽  
Jinkwon Kim
Keyword(s):  
Statin Therapy ◽  
Coil Embolization ◽  
Primary Outcome ◽  
Cox Regression ◽  
Cerebral Aneurysms ◽  
Time Dependent ◽  
Lipid Lowering ◽  
Surgical Clipping ◽  
The Impact

OBJECTIVECerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.METHODSThis was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.RESULTSA total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).CONCLUSIONSConsistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.

Imputing missing time-dependent covariate values for the discrete time Cox model

2019 ◽  
Vol 29 (8) ◽  
pp. 2074-2086
Author(s):  
Havi Murad ◽  
Rachel Dankner ◽  
Alla Berlin ◽  
Liraz Olmer ◽  
Laurence S Freedman
Keyword(s):  
Discrete Time ◽  
Missing Values ◽  
Cox Regression ◽  
Cox Model ◽  
Missing At Random ◽  
Time Dependent ◽  
Outcome Variable ◽  
Sequential Approach ◽  
Random Patterns ◽  
Event Times

We describe a procedure for imputing missing values of time-dependent covariates in a discrete time Cox model using the chained equations method. The procedure multiply imputes the missing values for each time-period in a time-sequential manner, using covariates from the current and previous time-periods as well as the survival outcome. The form of the outcome variable used in the imputation model depends on the functional form of the time-dependent covariate(s) and differs from the case of Cox regression with only baseline covariates. This time-sequential approach provides an approximation to a fully conditional approach. We illustrate the procedure with data on diabetics, evaluating the association of their glucose control with the risk of selected cancers. Using simulations we show that the suggested estimator performed well (in terms of bias and coverage) for completely missing at random, missing at random and moderate non-missing-at-random patterns. However, for very strong non-missing-at-random patterns, the estimator was seriously biased and the coverage was too low. The procedure can be implemented using multiple imputation with the Fully conditional Specification (FCS) method (MI procedure in SAS with FCS statement or similar packages in other software, e.g. MICE in R). For use with event times on a continuous scale, the events would need to be grouped into time-intervals.

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 ◽  
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.

Optimal timing of radical cystectomy after neoadjuvant chemotherapy in muscle invasive bladder cancer (MIBC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 509-509
Author(s):  
Saurabh Parasramka ◽  
Janeesh Sekkath Veedu ◽  
Quan Chen ◽  
Bin Huang ◽  
Peng Wang ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Survival Benefit ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Optimal Timing ◽  
Current Standard ◽  
Time Period ◽  
The Impact

509 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with bilateral pelvic lymph node dissection is the current standard of care for MIBC. Pathologic downstaging with NAC is an important surrogate endpoint and associated with overall survival benefit. There have been questions about the impact of delay in definitive surgery because of NAC. The optimal timing of surgery from the start of NAC is uncertain. We studied this question using National Cancer Database (2004-2015). Methods: We identified patients with MIBC (cT2-T4aN0M0 & cT1-T4aN1M0) who received NAC within 6 months of diagnosis and underwent surgery between 10 weeks and 9 months of the start day of NAC. We excluded patients who died within 30 days of surgery. Time period was stratified into three cohorts; 11-16, 17-24, and ≥25 weeks from the start day of NAC. Descriptive analysis, Kaplan-Meier plots, Log-Rank tests for univariate and proportional hazards models for multivariate survival analyses were performed. Results: 3709 patients were identified; 75% were males, 77% cases were cT2 and 73% had charlson-deyo score (CS) of '0'. Median time for surgery 10 weeks after start of NAC was 118 days. Forty-two (42%) had surgery in 11-16, 47% in 17-24 and 9.9% in ≥25 weeks. Majority (60%) were treated at academic and 24% at comprehensive community. Only 29% achieved complete pathological complete response rate (Tis or T0). On univariate analysis receiving NAC within 3 months of diagnosis was significantly associated with survival benefit (p < 0.001). Cox-regression results showed that patients who underwent surgery in 11-16 and 17-24 week time period had significantly better survival than > 25 week group with HR of 0.84 (0.71- 0.98) and 0.82 (0.70-0.97) respectively. In addition patients with CS of '0' had better survival with HR 0.78 (0.62-0.90) and > 75 years of age was associated with worse survival HR 1.73 (1.35-2.22). Conclusions: Our study indicates that appropriate patients with MIBC benefit from receiving surgery within 24 weeks of starting NAC. However, randomized prospective study is warranted to further explore the role of delay of surgery from NAC.

scholarly journals Effect of highly active anti-retroviral treatment on TB incidence among HIV infected children and their clinical profile, retrospective Cohort study, South West Ethiopia

2020 ◽  
Author(s):  
Firew Tiruneh Tiyare ◽  
Yared Deyas Deyas
Keyword(s):  
Cohort Study ◽  
Key Words ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Antiretroviral Treatment ◽  
Structural Model ◽  
Clinical Profile ◽  
Marginal Structural Model ◽  
Highly Active ◽  
The Impact

Abstract Background: Children younger than 15 years, carries almost 80% of the global burden of HIV/ AIDS. Nearly, 50% of cases of tuberculosis are attributed to HIV infection. HIV worsen the progression of latent TB to active TB disease. Despite antiretroviral treatment has shown marked reduction in Tuberculosis incidence , TB continues to occur in Sub Saharan country including Ethiopia. The effect of highly active antiretroviral treatment is quite successful in developed country while in developing country TB/HIV co-infection remains perplexing among children on the treatment. The aim of the study was to investigate the impact of ART on the incidence of tuberculosis among Children infected with HIV in southwest Ethiopia. Methods: A retrospective cohort study was conducted on randomly selected 800 samples from ART clinic; between 2009 to 2014. We used chi-square test, and Mann-WhitneyU test to compare HAART naïve and HAART cohort. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. Result: A total of 844 children were followed for 2942.99 child-years. The children were observed for a median of 51 months with IQR 31 and for a total of 2942.99 child-years. From 506 OIs that occurred, the most common reported OIs were Pneumonia (22%) and TB (23.6 %). The overall TB incidence rate was 7.917 per 100 child years (95% CI, 6.933-9.002). Whereas among HAART (7.667 per 100 -years (95% CI, 6.318-9.217) and 8.1686 per 100 person-years (95% CI 6.772-9.767) for HAART naïve. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.642 (95% CI 0.442-0.931, p<0.02) Conclusions: HAART reduced the hazard of TB in HIV-infected children by 36%. This is by far less than expected. Key Words- TB incidence, HAART, Clinical Profile ted children by 36%. This is by far less than expected. Key Words- TB incidence, HAART, Clinical Profile

scholarly journals Asymmetric leaflet tethering is associated with worse outcomes after edge-to-edge mitral valve repair for secondary mitral regurgitation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Stolz ◽  
M Orban ◽  
D Braun ◽  
P Doldi ◽  
M Orban ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Mitral Valve Repair ◽  
Cox Regression ◽  
Cox Model ◽  
Operating Characteristics ◽  
Valve Repair ◽  
Cox Regression Analysis ◽  
Secondary Mitral Regurgitation ◽  
The Impact

Abstract Background The impact of mitral valve (MV) tethering patterns on outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TEER) for severe secondary mitral regurgitation (SMR) is unknown. Purpose The purpose of this study was to evaluate the impact of asymmetric postero-anterior and medio-lateral MV leaflet tethering on procedural and survival outcomes after TEER for SMR. Methods Symmetry of postero-anterior leaflet tethering was defined as the ratio of the posterior to anterior MV leaflet angle (PLA/ALA) in the central MV segment 2. The ratio of the tenting area between MV segments 3 and 1 (S3/S1 ratio) was defined as medio-lateral tethering symmetry. We used receiver operating characteristics and a proportional Cox model to identify cut-off values of asymmetric postero-anterior and medio-lateral tethering for prediction of two-year survival after TEER. Results 178 patients receiving TEER for SMR were included. Asymmetric postero-anterior tethering was observed in 67 patients (37.6%, PLA/ALA ratio cut-off &gt;1.54). Medio-lateral tethering was asymmetric in 49 patients (27.5%, S3/S1 ratio cut-off &gt;1.49). MR was reduced to MR ≤2+ in 91.6% of patients, while postprocedural MR remained higher in the presence of asymmetric postero-anterior tethering (p=0.01). After adjustment for potential clinical and echocardiographic confounders, multivariable Cox regression analysis confirmed asymmetric postero-anterior tethering (HR=2.77, CI=1.43–5.38, p&lt;0.01) and asymmetric medio-lateral tethering (HR=2.90, CI=1.54–5.45, p&lt;0.01) as independent predictors for two-year survival. Conclusions Asymmetric postero-anterior and medio-lateral MV leaflet tethering patterns independently increase two-year all-cause mortality in patients undergoing TEER for SMR. Detailed echocardiographic patient selection might improve outcomes after TEER. FUNDunding Acknowledgement Type of funding sources: None. Postero-anterior tethering Medio-lateral tethering

scholarly journals Impact of the cardio-hepatic syndrome on outcomes after transcatheter mitral valve edge-to-edge repair

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Stolz ◽  
M Orban ◽  
N Karam ◽  
E Lubos ◽  
M Wild ◽  
...  
Keyword(s):  
Liver Function ◽  
Cox Regression ◽  
Cox Model ◽  
Hepatic Function ◽  
Gamma Glutamyl Transferase ◽  
Prognostic Impact ◽  
Laboratory Parameters ◽  
Glutamyl Transferase ◽  
The Impact

Abstract Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p&lt;0.01). In a multivariate Cox regression model, CHS was identified as a strong and independent predictor of increased two-year mortality (hazard ratio 1.49, p=0.03). In patients with successful MR reduction ≤2+ (90.7% of patients), parameters of hepatic function significantly improved from baseline to follow-up (−0.2 mg/dl for bilirubin; −21 U/l for GGT, respectively, p&lt;0.01), while they did not in case of residual postprocedural MR &gt;2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. FUNDunding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER

scholarly journals Risk factors for outbreaks of COVID-19 in care homes following hospital discharge: a national cohort analysis

2020 ◽  
Author(s):  
Chris Emmerson ◽  
James P Adamson ◽  
Drew Turner ◽  
Mike B Gravenor ◽  
Jane Salmon ◽  
...  
Keyword(s):  
Hospital Discharge ◽  
Cox Regression ◽  
Care Home ◽  
Cohort Analysis ◽  
Time Dependent ◽  
Care Homes ◽  
Health Board ◽  
High Morbidity ◽  
Discharge From Hospital ◽  
The Impact

Abstract Background Adult residential and nursing care homes are settings in which older and often vulnerable people live in close proximity. This population experiences a higher proportion of respiratory and gastrointestinal illnesses than the general population and has been shown to have a high morbidity and mortality in relation to COVID-19. Methods We examined the number of hospital discharges to all Welsh adult care homes and the subsequent outbreaks of COVID-19 occurring over an 18 week period 22 February and 27 June 2020. A Cox proportional hazards regression model was used to assess the impact of time-dependent exposure to hospital discharge on the incidence of the first known outbreak, over a window of 7-21 days after discharge, and adjusted for care home characteristics (including size, type of provision and health board). Results A total of 1068 care homes were monitored; 330 homes experienced an outbreak of COVID-19, and 511 homes received a discharge from hospital over the study period. The exposure to discharge from hospital was not associated with a significant increase in the risk of a new outbreak (hazard ratio 1.15, 95% CI 0.89, 1.49, p = 0.28), after adjusting for care home size, which was by far the most significant predictor. Hazard ratios (95% CI) in comparison to homes of <10 residents were: 3.4 (2.0, 5.8) for 10-24 residents; 8.3 (5.0, 13.8) for 25-49 residents; and 17.3 (9.6, 31.1) for homes of 50+ residents. When stratified for care home size, the outbreak rates were very similar for periods when homes were exposed to a hospital discharge, in comparison to periods when homes were unexposed. Conclusion Our analyses showed that large homes were at considerably greater risk of outbreaks throughout the epidemic, and after adjusting for care home size, a discharge from hospital was not associated with a significant increase in risk. Keywords: COVID-19, care homes, hospital discharge, outbreak, time dependent Cox regression

Sign in / Sign up

Export Citation Format

Share Document