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.

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.

Significance of tertiary pattern 5 in patients with gleason score 7 after radical prostatectomy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 117-117
Author(s):  
Jiakun Li ◽  
Yaochuan Guo ◽  
Shi Qiu ◽  
Mingjing He ◽  
Kun Jin ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Gleason Score ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Strong Association ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Gleason Pattern ◽  
Cox Proportional Hazards Models

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.

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.

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.

Comparison of cetuximab (Cmab) with panitumumab (Pmab) monotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 663-663
Author(s):  
Akira Ueda ◽  
Satoshi Yuki ◽  
Takahide Sasaki ◽  
Yoshimitsu Kobayashi ◽  
Ayumu Hosokawa ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Wild Type ◽  
Significant Difference

663 Background: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) such as Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Monotherapy with Cmab or Pmab demonstrated the effectiveness in salvage-line, and the direct comparison was reported in ESMO 2013 (ASPECCT trial). Methods: Data of 31 pts with mCRC treated by monotherapy with Cmab (HGCSG0901) and 51 pts by monotherapy with Pmab (HGCSG1002) registered from 27 institutions in Japan. Comparison of Cmab with Pmab was retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab vs. Pmab); male/female 20/11 vs. 27/24, median age (range) 65(44-76) vs. 64(44-81), PS 0-1/2-3 21/10 vs. 46/5, number of metastatic organs 1-2/3- 22/9 vs. 25/16. Skin toxicity was common adverse events and was generally similar in two groups. MST was 8.4 months in the Cmab and 8.1 months in the Pmab (p = 0.32). PFS was 3.8 months in the Cmab, as compared with 3.1 months in the Pmab (p = 0.60); the corresponding response rate was 19.4% and 13.7% (p = 0.54). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.939, 95% CI 0.783-1.128, p = 0.503), nor PFS (HR 0.972, 95% CI 0.823-1.148, p = 0.735). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab monotherapy in the salvage-line treatment of pts with mCRC.

scholarly journals Profile of Patients with Novel Coronavirus Disease 2019 (COVID-19) in Osaka Prefecture, Japan: A Population-Based Descriptive Study

2020 ◽  
Vol 9 (9) ◽  
pp. 2925 ◽  
Author(s):  
Taro Takeuchi ◽  
Tomoka Imanaka ◽  
Yusuke Katayama ◽  
Tetsuhisa Kitamura ◽  
Tomotaka Sobue ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Patient Characteristics ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Common Symptom ◽  
Osaka Prefecture ◽  
Novel Coronavirus ◽  
Epidemiological Characteristics

Little is known about the epidemiological characteristics of patients with coronavirus disease 2019 (COVID-19) in Japan. This is a retrospective observational study of COVID-19 patients; study was conducted from February 1 to May 31, 2020. We used publicly collected data on cases of COVID-19 confirmed by polymerase chain reaction (PCR) testing in Osaka Prefecture, Japan. We described the patient characteristics. The Cox proportional-hazards model was applied to evaluate the association between factors (sex, onset month, age group, city of residence) and mortality, and hazard ratios (HRs) with 95% confidence intervals were estimated. During the study period, 5.7% (1782/31,152) of individuals who underwent PCR testing for COVID-19 showed positive results. Among 244 patients with information on symptoms, the most common symptom was fever (76.6%), followed by cough (44.3%). Of the 1782 patients, 86 patients died. Compared with those aged 0–59 years, higher mortality was observed among those aged 60–69 years (HR: 12.02 [3.37–42.93]), 70–79 years (HR: 44.62 [15.16–131.30]), 80–89 years (HR: 68.38 [22.93–203.89]), and ≥90 years (HR: 144.71 [42.55–492.15]). In conclusion, in Osaka Prefecture, Japan, the most common symptom was fever, and older adults had higher mortality among COVID-19 patients.

scholarly journals 466 PREVALENCE AND IMPACT OF FRAILTY IN PATIENTS HOSPITALISED WITH COVID-19. THE SALFORD EXPERIENCE IN WAVES 1 AND 2

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii14-ii18
Author(s):  
A Khan ◽  
F R Espinoza ◽  
T Kneen ◽  
A Dafnis ◽  
H Allafi ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Proportional Hazards ◽  
Hospital Admissions ◽  
Proportional Hazards Model ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Clinical Frailty Scale ◽  
Patient Demographics ◽  
Hazards Model

Abstract Introduction The COVID-19 pandemic has had an extensive impact on the frail older population, with significant rates of COVID-related hospital admissions and deaths amongst this vulnerable group. There is little evidence comparing the prevalence and impact of frailty amongst patients hospitalised with COVID-19 in wave 1 vs wave 2 of the pandemic. Methods Prospective observational study of all consecutive patients admitted to Salford Royal NHS Foundation Trust (SRFT) between 27th February and 28th of April 2020 (wave 1), and 1st October to 10th November 2020 (wave 2) with a diagnosis of COVID-19. The primary endpoint was in-hospital mortality. Patient demographics, co-morbidities, biochemical parameters, and frailty (using the Clinical Frailty Scale, score 1–4 = not frail, score 5–9 = frail) were collected. A Cox proportional hazards model associating wave and frailty with mortality was used. A logistic regression model was used to associate patient characteristics with wave. Both models adjusted for patient characteristics. Results A total of 700 patients were included (N = 429, wave 1; N = 271, wave 2). In wave 1, 42% (N = 180) were female; median age was 72; 37% (N = 160) were non-survivors, 49% (N = 212) were frail (CFS 5–9). In wave 2, 38% (N = 104) were female; median age was 73; 30% (N = 80) were non-survivors, 39% (N = 106) were frail. There was a reduction in mortality in wave 2, aHR = 0.71 (95% CI 0.53–0.94). Frailty was associated with increased mortality, after adjustment for age, wave and other patient characteristics. Patients were more frail in wave 1, and the effect of frailty was more pronounced in wave 1 vs wave 2. Conclusion Frailty is highly prevalent amongst patients of all ages admitted to SRFT with COVID-19. Higher scores of frailty are associated with increased mortality.

Methods for displaying and calibration of Cox proportional hazards models

2017 ◽  
Vol 232 (1) ◽  
pp. 105-115
Author(s):  
Chrianna I Bharat ◽  
Kevin Murray ◽  
Edward Cripps ◽  
Melinda R Hodkiewicz
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Explanatory Power ◽  
Cox Proportional Hazards ◽  
Remaining Useful Life ◽  
Cox Proportional Hazards Model ◽  
Data Set ◽  
Proportional Hazards Models ◽  
Hazards Model ◽  
Cox Proportional Hazards Models

Cox proportional hazards modelling is a widely used technique for determining relationships between observed data and the risk of asset failure when model performance is satisfactory. Cox proportional hazards models possess good explanatory power and are used by asset managers to gain insight into factors influencing asset life. However, validation of Cox proportional hazards models is not straightforward and is seldom considered in the maintenance literature. A comprehensive validation process is a necessary foundation to build trust in the failure models that underpin remaining useful life prediction. This article describes data splitting, model discrimination, misspecification and fit methods necessary to build trust in the ability of a Cox proportional hazards model to predict failures on out-of-sample assets. Specifically, we consider (1) Prognostic Index comparison for training and test sets, (2) Kaplan–Meier curves for different risk bands, (3) hazard ratios across different risk bands and (4) calibration of predictions using cross-validation. A Cox proportional hazards model on an industry data set of water pipe assets is used for illustrative purposes. Furthermore, because we are dealing with a non-statistical managerial audience, we demonstrate how graphical techniques, such as forest plots and nomograms, can be used to present prediction results in an easy to interpret way.

Predictors of Mortality in People with Recent-onset Gout: A Prospective Observational Study

2016 ◽  
Vol 44 (3) ◽  
pp. 368-373 ◽  
Author(s):  
Zoë L. Vincent ◽  
Greg Gamble ◽  
Meaghan House ◽  
Julie Knight ◽  
Anne Horne ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Disease Duration ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Recent Onset ◽  
Risk Of Death ◽  
Increased Risk ◽  
Cox Proportional Hazard Regression

Objective.To determine mortality rates and predictors of death at baseline in people with a recent onset of gout.Methods.People with gout disease duration < 10 years were recruited from primary and secondary care settings. Comprehensive clinical assessment was completed at baseline. Participants were prospectively followed for at least 1 year. Information about death was systematically collected from primary and secondary health records. Standardized mortality ratios (SMR) were calculated and risk factors for mortality were analyzed using Cox proportional hazard regression models.Results.The mean (SD) followup duration was 5.1 (1.6) years (a total 1511 patient-yrs accrued). Of the 295 participants, 43 (14.6%) had died at the time of censorship (SMR 1.96, 95% CI 1.44–2.62). In the reduced Cox proportional hazards model, these factors were independently associated with an increased risk of death from all causes: older age (70–80 yrs: HR 9.96, 95% CI 3.30–30.03; 80–91 yrs: HR 9.39, 95% CI 2.68–32.89), Māori or Pacific ethnicity (HR 2.48, 95% CI 1.17–5.29), loop diuretic use (HR 3.99, 95% CI 2.15–7.40), serum creatinine (per 10 µmol/l change; HR 1.04, 95% CI 1.00–1.07), and the presence of subcutaneous tophi (HR 2.85, 95% CI 1.49–5.44). The presence of subcutaneous tophi was the only baseline variable independently associated with both cardiovascular (CV) cause of death (HR 3.13, 95% CI 1.38–7.10) and non-CV cause of death (HR 3.48, 95% CI 1.25–9.63).Conclusion.People with gout disease duration < 10 years have an increased risk of death. The presence of subcutaneous tophi at baseline is an independent predictor of mortality, from both CV and non-CV causes.

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