Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia

AbstractAfter analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab–containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14–0.37; p < 0.0001) and 0.40 (0.22–0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16–0.27; p < 0.0001) and 0.29 (0.21–0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22–0.63; p = 0.0003) for PFS and 0.53 (0.27–1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

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Overall survival (OS) with docetaxel (D) vs novel hormonal therapy (NHT) with abiraterone (A) or enzalutamide (E) after a prior NHT in patients (Pts) with metastatic prostate cancer (mPC): Results from a real-world dataset.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5537 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5537-5537 ◽

Cited By ~ 1

Author(s):

Umang Swami ◽

Jennifer Anne Sinnott ◽

Ben Haaland ◽

Benjamin Louis Maughan ◽

Nityam Rathi ◽

...

Keyword(s):

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Single Agent ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Metastatic Setting ◽

Subgroup Analyses ◽

Icd Codes

5537 Background: NHT (A and E) are approved first-line (1L) treatment (Rx) for mPC. After progression on NHT, Rx include either alternate NHT or D. However, OS from a randomized trial comparing NHT vs D after progression on 1L NHT has not been reported. Methods: Pts data were extracted from the Flatiron Health EHR-derived de-identified database. Inclusion: diagnosis of mPC; 1L Rx with single agent A or E only, single-agent Rx with alternate NHT (E or A) or D in second line (2L). Exclusion: > 180 days between date of diagnosis of mPC and date of next visit to ensure Pts were actively engaged in care at data-providing site; Rx with NHT in non-metastatic setting, any prior exposure to D. OS was compared using Cox proportional hazards model stratified by Rx propensity score. Each Pts’ probability of receiving D (rather than NHT) was modeled via a random forest based on Pts and disease characteristics which may drive treatment selection. These included pre-2L Rx ECOG scores, PSA, LDH, ALPH, Hb, age, ICD codes for liver metastasis, diabetes, neuropathy, and heart failure; insurance payer, year of start of 2L Rx, time on 1 L NHT, Gleason score, PSA at the original diagnosis of mPC. Subgroup analyses included 1L Rx duration < 12 mos. Results: 1165 Pts between 2/5/2013 to 9/27/2019 were eligible. Median follow up 8 mos (range 0.1-64.5). Median OS after 1L A was higher with E as compared to D (15.7 vs. 9.4 mos). Median OS after 1L E was higher with A as compared to D (13.3 vs. 9.7 mos) (table). Propensity distributions were overlapping among Rx arms and showed only modest imbalance. In 2L, D had a worse adjusted hazard ratio of 1.29 and 1.35 as compared to E and A respectively (p < 0.05). Similar results were seen with 1L Rx duration of < 12 mos (p < 0.05). Conclusions: These hypothesis-generating data provide real-world OS estimates with 2L D & NHT in mPC. In propensity-stratified analyses, mPC Pts who progressed on NHT had a worse OS with 2L D as compared to alternate NHT. Results were consistent in unadjusted analysis & subgroup analyses of 1L Rx < 12 mos. Results are subject to residual confounding and missingness. After prospective validation these data may aid in Rx sequencing, Pts counselling, and design of future clinical trials in this setting. [Table: see text]

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Multiple immune-related adverse events and anti-tumor efficacy: real-world data on various solid tumors

10.21203/rs.2.21095/v1 ◽

2020 ◽

Author(s):

Keitaro Shimozaki ◽

Yasutaka Sukawa ◽

Noriko Beppu ◽

Isao Kurihara ◽

Shigeaki Suzuki ◽

...

Keyword(s):

Retrospective Study ◽

Adverse Events ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Checkpoint Inhibitors ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

University Hospital ◽

Real World Data

Abstract Background Immune checkpoint inhibitors have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in the real-world practice. Methods We conducted a retrospective study on patients with recurrent or metastatic non-small cell lung cancer, melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model. Results Among 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. OS in patients with multiple irAEs was significantly longer than that in patients with single irAE (42.3 months vs. 18.8 months; hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25–0.93; P = 0.03). Moreover, OS from the development of a second irAE in those with multiple irAEs was longer than that from the development of the first irAE in patients with single irAEs (median OS, 26.9 months vs. 17.7 months, respectively; HR, 0.59; 95% CI, 0.30–1.14; P = 0.11). Conclusions Our single-center retrospective study revealed a remarkable tendency associating the development of multiple irAEs with favorable prognoses.

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The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009635 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009635

Author(s):

Selma Regina Penha Silva Cerqueira ◽

Patrícia Duarte Deps ◽

Débora Vilela Cunha ◽

Natanael Victor Furtunato Bezerra ◽

Daniel Holanda Barroso ◽

...

Keyword(s):

Cohort Study ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Significant Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Protective Effects ◽

Bcg Vaccination ◽

Patients At Risk

Background Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. Methodology/Principal findings We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93–13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04–4.06) were significant risk factors for COVID-19. Conclusions/Significance Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

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Real-World Use of FLT3 Tyrosine Kinase Inhibitors in Patients with Relapsed/Refractory FLT3 mutation-Positive Acute Myeloid Leukemia in the United States

Blood ◽

10.1182/blood-2021-145387 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 5033-5033

Author(s):

David L. Grinblatt ◽

Wei Han ◽

David Nimke ◽

Qi Feng ◽

Loretta Sullivan ◽

...

Keyword(s):

Real World ◽

Treatment Duration ◽

Kinase Inhibitors ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Treatment Patterns ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Tki Treatment

Abstract Background: FLT3 tyrosine kinase inhibitors (TKIs) have improved outcomes in clinical trials for patients with FLT3 mutation-positive acute myeloid leukemia (FLT3mut+ AML). Gilteritinib is the first FDA-approved (11/28/2018) targeted therapy for relapsed/refractory (R/R) FLT3mut+ AML in adults, although two other multikinase inhibitors, midostaurin and sorafenib, are used off-label in this population. This analysis characterized treatment duration for these three drugs in R/R FLT3mut+ AML, as little is known about the treatment of patients receiving a FLT3 inhibitor in the real world. Aim/Objective: To describe real-world treatment patterns of patients newly initiating a FLT3 TKI for R/R AML following the launch of gilteritinib. Methods: This was a post hoc analysis of a US-based retrospective cohort study using IBM MarketScan claims data (1/1/2007-10/30/2020) to evaluate real-world treatment patterns. Adult patients (≥18 years) with R/R AML who newly initiated a FLT3 TKI (ie, ≥1 claim for gilteritinib, midostaurin, or sorafenib) on or after 12/1/2018 were eligible for inclusion. Included patients were required to have continuous enrollment starting 180 days prior to first AML diagnosis through first FLT3 TKI initiated for R/R AML on or after 12/1/2018 (index date). FLT3 TKI treatment duration was calculated as the difference between the first claim and the last day of supply or end of enrollment/study, whichever occurred first. Treatments that were not discontinued prior to the end of the study period (10/30/2020) were censored. Treatment duration was estimated using Kaplan-Meier analysis, and the hazard ratio for discontinuation was estimated with a Cox proportional hazards model. Additional subgroup analyses were conducted based on prior FLT3 TKI exposure for R/R AML and use of FLT3 TKI therapy alone or in combination with chemotherapy. Data from the ProMetrics specialty pharmacy database (12/6/2018-3/3/2021) were also analyzed to establish a benchmark for gilteritinib and validate the treatment duration in the MarketScan results. Results: A total of 65 patients newly initiating FLT3 TKIs for R/R AML were identified in the MarketScan database. Mean patient age was 53.4 years and mean Quan-Charlson Comorbidity index score at baseline was 5.1. Most patients initiating FLT3 TKI therapy received gilteritinib (n=44 [68%]). Patients initiating gilteritinib compared with other FLT3 TKIs had the highest prior history of high-intensity chemotherapy (n=24 [47%]) and hematopoietic stem cell transplantation (n=16 [31%]). Midostaurin was the most common prior TKI for patients who initiated sorafenib (n=6 [50%]) or gilteritinib (n=28 [55%]). The median (95% CI) treatment duration was 150 (73-260) days for gilteritinib (n=51), 60 (15-210) days for sorafenib (n=12), and 54 (28-268) days for midostaurin (n=12). Treatment duration was significantly longer for patients receiving gilteritinib compared with midostaurin (P=.0018) and sorafenib (P=.0016) in the Cox proportional hazards model (Table) and the Kaplan-Meier analysis (P=.0021) (Figure). Differences in gilteritinib duration in patients with prior TKI treatment versus no prior TKI treatment and patients who used a FLT3 TKI alone versus in combination with chemotherapy were not statistically significant (Table). The median gilteritinib treatment duration in the MarketScan data (150 days) was aligned with the median duration in the ProMetrics specialty pharmacy data (154 days), which validates the MarketScan results. Conclusions: This early look at treatment patterns suggests a median duration of therapy for gilteritinib of 150 days. Importantly, gilteritinib treatment duration does not appear to differ based on prior TKI treatment or overlapping use with chemotherapy. Small sample sizes precluded adjusted comparisons between the treatments. Gilteritinib was the most commonly used treatment. The availability of new targeted therapies such as gilteritinib is promising for patients with R/R FLT3mut+ AML and is changing the therapeutic landscape for this aggressive AML subtype. Figure 1 Figure 1. Disclosures Grinblatt: Astellas Pharma, Inc.: Consultancy; Bristol Myers Squibb: Consultancy; Astra Zeneca: Consultancy; AbbVie: Consultancy. Han: Astellas Pharma, Inc.: Current Employment. Nimke: Astellas Pharma, Inc.: Current Employment. Feng: Astellas Pharma, Inc.: Current Employment. Sullivan: Astellas Pharma, Inc.: Current Employment. Pandya: Astellas Pharma, Inc.: Current Employment.

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Abstract 16398: Comparison of Major Bleeding Risk and Associated Costs Among Newly Anticoagulated Non-valvular Atrial Fibrillation Patients

Circulation ◽

10.1161/circ.132.suppl_3.16398 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Steven Deitelzweig ◽

Amanda Bruno ◽

Natalie Tate ◽

Augustina Ogbonnaya ◽

Manan Shah ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model

Real-world evidence highlighting the risks and benefits of novel oral anticoagulants (NOCAs) is lacking. This study compared major and clinically relevant non-major (CRNM) bleeding risk and costs among non-valvular atrial fibrillation (NVAF) patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin. A retrospective analysis of NVAF patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin was conducted using PharMetrics Plus data from 1/ 2012 - 9/ 2014. Patients were indexed on the date of the first anticoagulant prescription, and were required to be ≥18 years old and have CHA 2 DS 2 -VASc score > 0 and ≥ 1 month of follow-up. Patients were followed until discontinuation (≥30-day gap in treatment), treatment switch, end of continuous enrollment, 1 year post-index, or end of study. Major and CRNM bleeding, and bleeding-related costs were measured. Cox proportional hazards model was used to examine the association between anticoagulants and risk of bleeding and GLM was used to evaluate bleeding-related costs. The study included 24,573 NVAF patients; distributed as apixaban 11.7%, dabigatran 12.0%, rivaroxaban 36.7%, and warfarin 39.6%. Mean age was 64.4 and 66.5% were males. HAS-BLED and CHA 2 DS 2 -VASc scores averaged 2.0 and 2.7, respectively. After adjusting for differences in baseline characteristics, when compared to apixaban patients, rivaroxaban (HR: 1.5; P =0.0013) and warfarin (HR: 1.7; P <0.0001) patients were more likely to have major bleeding, and dabigatran (HR: 1.3; P =0.0030), rivaroxaban (HR: 1.7; P <0.0001), and warfarin (HR: 1.4; P <0.0001) patients were more likely to have CRNM bleeding. Major bleeding risk was similar between apixaban and dabigatran patients. Major and CRNM bleeding costs, when compared to apixaban patients ($154 and $18), were significantly higher for dabigatran ($457; P <0.0001 and $39; P <0.0001), rivaroxaban ($420; P <0.0001 and $61; P <0.0001), and warfarin ($511; P <0.0001 and $63; P <0.0001) patients. Among anticoagulant-naive moderate-to-high risk NVAF patients encountered in real-world clinical setting, major bleeding was lower with apixaban compared to warfarin and rivaroxaban. Bleeding costs were lower with apixaban compared to alternative NOACs and warfarin.

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Mortality After Remdesivir Treatment of Pneumonia in Hospitalised Patients with Laboratory Confirmed COVID-19: National Data in the Italian Real-World Practice Collected by the AIFA Monitoring Register

10.21203/rs.3.rs-525476/v1 ◽

2021 ◽

Author(s):

Pierluigi Russo ◽

Pier Paolo Olimpieri ◽

Simone Celant ◽

Antonietta Colatrella ◽

Luca Tomassini ◽

...

Keyword(s):

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Low Flow ◽

Female Ratio ◽

Healthcare Data ◽

Kaplan Meier ◽

Hospitalised Patients

Abstract The Italian Medicines Agency (AIFA) granted reimbursement for remdesivir (Veklury®) exclusively to COVID-19 patients with pneumonia requiring supplemental low-flow oxygen therapy. A monitoring registry was instituted to manage vials delivery and to control use appropriateness in Italy. The registry collected healthcare data on remdesivir use across all Italian hospitals. Mortality by day 15 and 29 was estimated using the Kaplan-Meier estimator. The Cox proportional-hazards model was applied to analyse the risks connected to patient’s background features relative to all-cause mortality by day 29. 16473 SARS-CoV-2 positive patients were included in the registry with a mean age of 66.3 years and a male/female ratio of 2/1. 2279 deaths were registered. The Kaplan–Meier estimate of national mortality by day 15 was 7.1% (95%CI: 6.7%-7.5%) while mortality by day 29 was 11.7% (95%CI: 11.2%-12.2%). Cox-adjusted estimates by day 29 shown 18.8% (95%CI: 17.2% -20.3%) mortality in the class 65 years or older. This study provided the largest figure on mortality after the remdesivir treatment of SARS-Cov2 pneumonia in the real-world practice, and it also argued for efficacy of remdesivir in reducing mortality in patients older than 65 years when compared to data from the national surveillance.

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Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.110 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 110-110 ◽

Cited By ~ 5

Author(s):

Sean Khozin ◽

Mark S. Walker ◽

Monika Jun ◽

Li Chen ◽

Edward Stepanski ◽

...

Keyword(s):

Autoimmune Disease ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

The Impact

110 Background: Anecdotal and early evidence suggest ICIs are being used in patients with advanced malignancies and history of AD, despite such patients being typically excluded from traditional clinical trials. We compared the outcomes of patients with or without AD, all of whom had ICI treatment for aNSCLC. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in ASCO’s CancerLinQ. Patients with Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 visits from Jan 2011 to Nov 2018 were included. AD status prior to ICI treatment was identified using ICD-9/ICD-10 codes or AD medications (including steroids). Symphony claims data were linked via tokenization to build cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS) and overall survival (OS) were compared across the two cohorts using the log-rank test. Cox Proportional Hazards Model was used to adjust for covariates. Adverse events (AEs) were compared using Chi-Square and Fisher’s Exact Test. Active AD was defined as evidence of autoimmune disease in the year prior to starting ICIs. Results: Among 2425 patients with aNSCLC treated with ICIs, AD was present in 22% (N=538). Median OS in all patients was 12.4 months (95% CI 11.3-13.5). TTD, TTNT, rwPFS and OS did not differ between the two cohorts (Table). There was no association between AD status and outcomes. There was no increased incidence of AEs in the AD group; however a sub-analysis among patients with active AD showed higher rates of select AEs including endocrine, GI and blood disorders. Conclusions: This analysis demonstrates that patients with evidence of AD prior to receiving ICI have similar outcomes compared to patients with no evidence of AD. Further research is needed to better understand the impact of active AD on the risk of AEs and patient outcomes. [Table: see text]

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Abstract P60: The Effect of Angiotensin Receptor Blocker/Calcium Channel Blocker Single Pill Combination Therapy on Adherence to Antihypertensive Treatment

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap60 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Feng Zeng ◽

Laquesha Andrews ◽

Bimal V Patel

Keyword(s):

Combination Therapy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Single Agent ◽

Olmesartan Medoxomil ◽

Geographic Region ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Single Pill ◽

The Impact

Objective: To evaluate the impact of ARB/CCB single pill combination therapy on adherence to antihypertensive (AHY) treatment. Methods: A retrospective data analysis was performed using pharmacy claims data from a national pharmacy benefit management company. The study included patients who were newly initiated on ARB/CCB treatment between 01/01/2007 and 08/31/2008, age ≥18 years, and continuously enrolled in the same health plan for 6 months prior to and 13 months after starting ARB/CCB treatment. Patients who started either valsartan and amlodipine or amlodipine and olmesartan medoxomil ARB/CCB single pill combinations were assigned to the single pill combination (SPC) group. The ARB/CCB free combination (FC) group included patients who used a combination of single-agent ARB and CCB treatment. Outcome variables were persistence, defined as time to discontinuation of therapy, and adherence, defined as proportion of days covered (PDC) ≥0.80. Propensity score weighted multivariable regression models were used to estimate the impact of combination pill therapy. Covariates included age, gender, baseline comorbidities, insurance type, geographic region, copayment, and history of other AHY use. Results: The final sample contained 2,312 patients in the ARB/CCB FC group and 2,213 patients in the ARB/CCB SPC group. After adjustment for differences in baseline characteristics, a Cox proportional hazards model showed that patients in the SPC group were 24% less likely to discontinue ARB/CCB therapy as compared to patients in the FC group (HR 0.76, 95% CI 0.73-0.79, p<0.0001). A logistic model showed that patients in the SPC pill group had a 90% greater odds of being adherent compared to patients in the FC group (OR 1.90, 95% CI 1.75-2.08, p<0.0001). In both models, higher copayment (copayment $50 and above) was associated with poorer persistence and adherence in comparison to patients who faced copayment $0-$5: HR=1.15, p<0.001 and OR=0.67, p<0.0001. Conclusion: Patients using single pill combination ARB/CCB therapy were more likely to be persistent and adherent to treatment as compared to patients taking free combination therapy.

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Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽

10.1027/0227-5910/a000468 ◽

2018 ◽

Vol 39 (1) ◽

pp. 27-36 ◽

Cited By ~ 5

Author(s):

Kuan-Ying Lee ◽

Chung-Yi Li ◽

Kun-Chia Chang ◽

Tsung-Hsueh Lu ◽

Ying-Yeh Chen

Keyword(s):

Young People ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Birth Registry ◽

Data Set ◽

Parental Suicide ◽

The Impact ◽

Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

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Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

Journal of Neurosurgery ◽

10.3171/2018.12.jns182775 ◽

2020 ◽

Vol 132 (4) ◽

pp. 998-1005 ◽

Cited By ~ 4

Author(s):

Haihui Jiang ◽

Yong Cui ◽

Xiang Liu ◽

Xiaohui Ren ◽

Mingxiao Li ◽

...

Keyword(s):

Survival Benefit ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Characteristic Curve ◽

Extent Of Resection ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

High Grade ◽

Extensive Resection ◽

High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

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