Predicting self-reported depression after the onset of multiple sclerosis using genetic and non-genetic factors

2020 ◽  
pp. 135245852092107
Author(s):  
Frances M Wang ◽  
Mary F Davis ◽  
Farren BS Briggs
Keyword(s):  
Multiple Sclerosis ◽  
Prediction Model ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Genetic Risk Score ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Depression Risk ◽  
History Of ◽  
History Of Depression

Background: Persons with multiple sclerosis (PwMS) are disproportionately burdened by depression compared to the general population. While several factors associated with depression and depression severity in PwMS have been identified, a prediction model for depression risk has not been developed. In addition, it is unknown if depression-related genetic variants, including Apolipoprotein E ( APOE), would be informative for predicting depression in PwMS. Objective: To develop a depression prediction model for PwMS who did not have a history of depression prior MS onset. Methods: The study population included 917 non-Hispanic white PwMS. An optimized multivariable Cox proportional hazards model for time to depression was generated using non-genetic variables, to which APOE and a depression-related genetic risk score were included. Results: Having a mother who had a history of depression, having obstructive pulmonary disease, obesity and other physical disorders at MS onset, and affect-related symptoms at MS onset predicted depression risk (hazards ratios (HRs): 1.6–2.3). Genetic variables improved the prediction model’s performance. APOE ε4/ε4 and ε2/x conferred increased (HR = 2.5, p = 0.026) and decreased (HR = 0.65, p = 0.046) depression risk, respectively. Conclusion: We present a prediction model aligned with The Precision Medicine Initiative, which integrates genetic and non-genetic predictors to inform depression risk stratification after MS onset.

Abstract 17617: History of Bleeding and Outcomes with Apixaban versus Warfarin in Patients with Atrial Fibrillation in the ARISTOTLE Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Raffaele De Caterina ◽  
Ulrika Andersson ◽  
John H Alexander ◽  
M.Cecilia Bahit ◽  
Patrick J Commerford ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Major Bleeding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Channel Blockers ◽  
Chads2 Score ◽  
History Of

Background: History of bleeding is important in decisions for anticoagulation. We analyzed outcomes in relation to history of bleeding and randomized treatments in patients with atrial fibrillation (AF) in the ARISTOTLE trial. Methods: The on-treatment safety population included 18,140 patients receiving ≥1 dose of study drug, apixaban 5 mg bd (2.5 mg bd if 2 of the following: age >80 yrs; body weight <60 kg; or creatinine >133 μmol/L) or warfarin aiming for INR 2.0-3.0 (median TTR 66%), for a median of 1.8 yrs. Adjudicated outcomes in relation to randomization and history of bleeding were analyzed using a Cox proportional hazards model. Efficacy endpoints were analyzed in the intention-to-treat population. Results: A history of bleeding was reported in 3033 patients (16.7%), who more often were male (68% vs 64%, p <0.0005); with a history of prior stroke/TIA/systemic embolism (23% vs 19%, p <0.0001); diabetes (27% vs 24%, p=0.0010); higher CHADS2 score (CHADS2 >3: 35% vs 29%), age (mean [SD] 71 [9] vs 69 [10], p <0001) and body weight (86 [21] vs 84 [21], p <0.0001); lower creatinine clearance (77 [33] vs 80 [33], p=0.0007) and mean systolic blood pressure (131 [17] vs 132 [16], p=0.0027). Calcium channel blockers, statins, non-steroidal anti-inflammatory drugs and proton pump inhibitors were used more often in patients with vs without a history of bleeding. Major bleeding was the only outcome event occurring more frequently in patients with vs without a history of bleeding, HR 1.7 (95% CI 1.4-2.3) with apixaban and 1.5 (1.2-1.0) with warfarin. Primary efficacy and safety outcomes in relation to randomization, see Table. Conclusions: In patients with AF, a history of bleeding was associated with several risk factors for stroke and bleeding and, accordingly, a higher bleeding risk during anticoagulation. Benefits with apixaban vs warfarin as to stroke, mortality and major bleeding, are however consistent irrespective of bleeding history.

Prognostic indicators of secondary progression in a paediatric-onset multiple sclerosis cohort in Kuwait

2015 ◽  
Vol 22 (8) ◽  
pp. 1086-1093 ◽  
Author(s):  
Saeed Akhtar ◽  
Raed Alroughani ◽  
Samar F Ahmed ◽  
Jasem Y Al-Hashel
Keyword(s):  
Multiple Sclerosis ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Adjusted Hazard Ratio ◽  
Secondary Progressive ◽  
Hazards Model

Background: The frequency of paediatric-onset multiple sclerosis (POMS) and the precise risk of secondary progression of disease are largely unknown in the Middle East. This cross-sectional cohort study assessed the risk and examined prognostic factors for time to onset of secondary progressive multiple sclerosis (SPMS) in a cohort of POMS patients. Methods: The Kuwait National MS Registry database was used to identify a cohort of POMS cases (diagnosed at age <18 years) from 1994 to 2013. Data were abstracted from patients’ records. A Cox proportional hazards model was used to evaluate the prognostic significance of the variables considered. Results: Of 808 multiple sclerosis (MS) patients, 127 (15.7%) were POMS cases. The median age (years) at disease onset was 16.0 (range 6.5–17.9). Of 127 POMS cases, 20 (15.8%) developed SPMS. A multivariable Cox proportional hazards model showed that at MS onset, brainstem involvement (adjusted hazard ratio 5.71; 95% confidence interval 1.53–21.30; P=0.010), and POMS patient age at MS onset (adjusted hazard ratio 1.38; 95% confidence interval 1.01–1.88; P=0.042) were significantly associated with the increased risk of a secondary progressive disease course. Conclusions: This study showed that POMS patients with brainstem/cerebellar presentation and a relatively higher age at MS onset had disposition for SPMS and warrant an aggressive therapeutic approach.

Effect of Physical Comorbidities on Risk of Depression in Multiple Sclerosis

2009 ◽  
Vol 11 (4) ◽  
pp. 161-165 ◽  
Author(s):  
Ruth Ann Marrie ◽  
Gary Cutter ◽  
Tuula Tyry ◽  
Denise Campagnolo ◽  
Timothy Vollmer
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Depression Scale ◽  
Epidemiologic Studies ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Research Committee ◽  
The North ◽  
Increased Risk

Depression in multiple sclerosis (MS) may be due to several factors, including the presence of physical comorbidities. Using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry, we examined whether individuals with MS and physical comorbidities have an increased risk of depression compared with those without physical comorbidities and whether they are more likely to remain untreated for depression. In 2006, NARCOMS participants reported their physical and mental comorbidities and completed the Center for Epidemiologic Studies Depression Scale (CESD). We defined a CESD score of 21 or higher as indicating probable major depression. Individuals with elevated CESD scores but no diagnosis of depression were considered undiagnosed. Forty-six percent of participants reported a lifetime history of depression. In a multivariable Cox proportional hazards model, reporting any physical comorbidity was associated with an increased risk of being diagnosed with depression (hazard ratio [HR], 2.20; 95% confidence interval [CI], 2.04–2.38) after MS onset and with an increased risk of diagnosed or undiagnosed depression (HR, 2.37; 95% CI, 2.21–2.54). After adjustment for education, participants with any physical comorbidity were more likely to report treatment for depression (odds ratio [OR], 1.67; 95% CI, 1.24–2.23). Patients with MS and physical comorbidities are at increased risk of depression, but they are more likely to be diagnosed and treated than MS patients without other chronic conditions.

Abstract 16688: Effects of Evolocumab in Patients With Prior Percutaneous Coronary Intervention: An Analysis From the Fourier Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Remo H Furtado ◽  
Antonio A Fagundes ◽  
Kazuma Oyama ◽  
Thomas A Zelniker ◽  
Minao Tang ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Absolute Risk ◽  
Coronary Revascularization ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Coronary Events

Introduction: Among patients with atherosclerotic cardiovascular disease (ASCVD), those with history of PCI represent an important population for potential high risk for cardiovascular (CV) events. We examined the clinical efficacy of the PCSK9 inibitor evolocumab in patients with prior PCI. Methods: FOURIER randomized 27,564 patients with ASCVD on statin therapy to evolocumab or placebo with a median follow-up of 2.2 yrs. The primary end point (PEP) was the composite of CV death, MI, stroke, unstable angina, or coronary revascularization; major coronary events were the composite of coronary death, MI, or coronary revascularization. The risk of events in patients with and without a history of PCI were compared in the placebo arm. The clinical benefit of evolocumab vs. placebo was compared using a Cox proportional hazards model. Results: 17,073 (62%) patients had prior PCI at baseline. Among patients in the placebo arm, those with prior PCI (N=8563) had a 1.6x higher rate of the PEP (16.8 vs 10.7%; adjusted HR 1.61; 95% CI 1.42-1.84 P<0.0001) and nearly double the rate of major coronary events (14.5 vs. 7.8%; P<0.0001; adjusted HR 1.72; 95% CI 1.49-1.99; Figure left). In patients with prior PCI, evolocumab reduced the risk of the PEP by 16% (HR 0.84; 95% CI 0.77-0.91; P<0.0001) and of major coronary events by 18% (HR 0.82; 95% CI 0.75-0.90, P<0.0001; Figure right), including a 30% reduction in fatal or non-fatal MI (P<0.001) and a 24% reduction in coronary revascularization (P<0.001). After the first year, there was a 25% reduction in major coronary events (HR 0.75, 95% CI 0.66-0.86, P<0.0001). The absolute risk reduction at 3 years with evolocumab for major coronary events was 2.8% in patients with prior PCI vs. 0.3% in those without. Conclusions: In a contemporary cohort with ASCVD on statin therapy, patients with prior PCI were at heightened risk for coronary events. Evolocumab was highly effective in this group, reducing major coronary events by 18% with a NNT at 3 years of only 36.

scholarly journals Survival Analysis and Prediction Model for Pulmonary Sarcomatoid Carcinoma Based on SEER Database

2021 ◽  
Vol 11 ◽  
Author(s):  
Mingjing Chen ◽  
Qiao Yang ◽  
Zihan Xu ◽  
Bangyu Luo ◽  
Feng Li ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Prediction Model ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Clinical Stage ◽  
Sarcomatoid Carcinoma ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Pulmonary Sarcomatoid Carcinoma ◽  
Testing Set

ObjectiveThis study aimed to investigate the incidence of the pulmonary sarcomatoid carcinoma (PSC), to compare the clinical characteristics and overall survival (OS) of patients with PSC and those with other non-small-cell lung cancer (oNSCLC), so as to analyze the factors affecting the OS of patients with PSC and construct a nomogram prediction model.MethodsData of patients with PSC and those with oNSCLC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database were collected. The age-adjusted incidence of PSC was calculated. The characteristics of patients with PSC and those with oNSCLC were compared, then the patients were matched 1:2 for further survival analysis. Patients with PSC were randomly divided into training set and testing set with a ratio of 7:3. The Cox proportional hazards model was used to identify the covariates associated with the OS. Significant covariates were used to construct the nomogram, and the C-index was calculated to measure the discrimination ability. The accuracy of the nomogram was compared with the tumor–node–metastasis (TNM) clinical stage, and the corresponding area under the curve was achieved.ResultsA total of 1049 patients with PSC were enrolled, the incidence of PSC was slowly decreased from 0.120/100,000 in 2004 to 0.092/100,000 in 2015. Before PSM, 793 PSC patients and 191356 oNSCLC patients were identified, the proportion of male, younger patients (&lt;65 years), grade IV, TNM clinical stage IV was higher in the PSC. The patients with PSC had significantly poorer OS compared with those with oNSCLC. After PSM, PSC still had an extremely inferior prognosis. Age, sex, TNM clinical stage, chemotherapy, radiotherapy, and surgery were independent factors for OS. Next, a nomogram was established based on these factors, and the C-indexs were 0.775 and 0.790 for the training and testing set, respectively. Moreover, the nomogram model indicated a more comprehensive and accurate prediction than the TNM clinical stage.ConclusionsThe incidence of PSC was slowly decreased. PSC had a significantly poor prognosis compared with oNSCLC. The nomogram constructed in this study accurately predicted the prognosis of PSC, performed better than the TNM clinical stage.

Analysis of Factors Associated With Outcome in Patients With Malignant Peritoneal Mesothelioma Undergoing Surgical Debulking and Intraperitoneal Chemotherapy

2003 ◽  
Vol 21 (24) ◽  
pp. 4560-4567 ◽  
Author(s):  
Andrew L. Feldman ◽  
Steven K. Libutti ◽  
James F. Pingpank ◽  
David L. Bartlett ◽  
Tatiana H. Beresnev ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Disease ◽  
Tumor Resection ◽  
Regional Chemotherapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
History Of

Purpose: Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. Patients and Methods: Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. Results: At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). Conclusion: Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

scholarly journals Duration of natalizumab therapy and reasons for discontinuation in a multiple sclerosis population

2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090248
Author(s):  
Devon S Conway ◽  
Carrie M Hersh ◽  
Haleigh C Harris ◽  
Le H Hua
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cox Proportional Hazards Models ◽  
Natalizumab Treatment ◽  
Relapsing Multiple Sclerosis

Objective To determine multiple sclerosis patient characteristics that predict a shorter duration of natalizumab treatment. Methods The Tysabri Outreach: Unified Commitment to Health database was reviewed to identify patients treated with natalizumab at our centers. Cox proportional hazards models were used to evaluate patient characteristics associated with shorter treatment durations on natalizumab. Associations were also assessed with respect to specific reasons for stopping natalizumab. Results We identified 554 patients who began and stopped natalizumab treatment during the observation period. The average disease duration at natalizumab initiation was 7.6 years, and the average number of infusions was 30. The multivariable Cox proportional hazards model identified greater age ( P = 0.035), longer disease duration ( P < 0.001), progressive relapsing multiple sclerosis phenotype ( P = 0.003), current smoking ( P = 0.031), and greater depression ( P = 0.026) as significant predictors for natalizumab discontinuation. Greater disability levels ( P = 0.022) and gadolinium-enhancing lesions on baseline magnetic resonance imaging ( P < 0.001) were significantly associated with longer natalizumab treatment. Individuals with progressive relapsing multiple sclerosis had a 14-fold increased hazard of discontinuing natalizumab due to inflammatory events ( P < 0.001) than those with relapsing–remitting multiple sclerosis. Smokers had an 80% increased hazard of discontinuation due to intolerance ( P = 0.008). Conclusions Our results suggest that smoking, depression, and a progressive relapsing multiple sclerosis phenotype are associated with shorter natalizumab treatment durations.

scholarly journals Confirmed disability progression provides limited predictive information regarding future disease progression in multiple sclerosis

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732199907
Author(s):  
Brian C Healy ◽  
Bonnie I Glanz ◽  
Elyse Swallow ◽  
James Signorovitch ◽  
Kaitlin Hagan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Information Criterion ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Lesion Volume ◽  
Disability Progression ◽  
Fit Statistics

Background Although confirmed disability progression (CDP) is a common outcome in multiple sclerosis (MS) clinical trials, its predictive value for long-term outcomes is uncertain. Objective To investigate whether CDP at month 24 predicts subsequent disability accumulation in MS. Methods The Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital includes participants with relapsing-remitting MS or clinically isolated syndrome with Expanded Disability Status Scale (EDSS) scores ≤5 (N = 1214). CDP was assessed as a predictor of time to EDSS score 6 (EDSS 6) and to secondary progressive MS (SPMS) using a Cox proportional hazards model; adjusted models included additional clinical/participant characteristics. Models were compared using Akaike’s An Information Criterion. Results CDP was directionally associated with faster time to EDSS 6 in univariate analysis (HR = 1.61 [95% CI: 0.83, 3.13]). After adjusting for month 24 EDSS, CDP was directionally associated with slower time to EDSS 6 (adjusted HR = 0.65 [0.32, 1.28]). Models including CDP had worse fit statistics than those using EDSS scores without CDP. When models included clinical and magnetic resonance imaging measures, T2 lesion volume improved fit statistics. Results were similar for time to SPMS. Conclusions CDP was less predictive of time to subsequent events than other MS clinical features.

scholarly journals Additive Hazard Regression Models: An Application to the Natural History of Human Papillomavirus

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Xianhong Xie ◽  
Howard D. Strickler ◽  
Xiaonan Xue
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Additive Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
History Of ◽  
Oncogenic Hpv ◽  
Hiv Negative

There are several statistical methods for time-to-event analysis, among which is the Cox proportional hazards model that is most commonly used. However, when the absolute change in risk, instead of the risk ratio, is of primary interest or when the proportional hazard assumption for the Cox proportional hazards model is violated, an additive hazard regression model may be more appropriate. In this paper, we give an overview of this approach and then apply a semiparametric as well as a nonparametric additive model to a data set from a study of the natural history of human papillomavirus (HPV) in HIV-positive and HIV-negative women. The results from the semiparametric model indicated on average an additional 14 oncogenic HPV infections per 100 woman-years related to CD4 count < 200 relative to HIV-negative women, and those from the nonparametric additive model showed an additional 40 oncogenic HPV infections per 100 women over 5 years of followup, while the estimated hazard ratio in the Cox model was 3.82. Although the Cox model can provide a better understanding of the exposure disease association, the additive model is often more useful for public health planning and intervention.

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