Prognostic Relevance of the Kinetics of Worsening of Cytopenias in Lower-Risk MDS: A Substudy From the European Leukemianet Low Risk MDS (EUMDS) Registry

Abstract Abstract 700 Purpose: Prognosis of lower (IPSS low/int-1) risk MDS is heterogeneous. Current prognostic systems rely on single time point cytopenia values (Hb level, ANC, PLT counts) at diagnosis (classical or revised IPSS [IPSS-R] Greenberg, Blood 2012) or during evolution (time-dependent IPSS/WPSS). Capturing the dynamics of continuous parameters can yield independent prognostic information as exemplified by lymphocyte time doubling in CLL. We analyzed the prognostic relevance of the kinetics of Hb, ANC and PLT in lower-risk MDS patients (pts) included in the prospective EUMDS registry. Methods: Among the first 1000 pts included in the EUMDS registry, those fulfilling the following criteria were analyzed here: a) IPSS low/int-1; b) ≥3 visits (planned every 6 months) with ≥12 months follow-up; c) not treated with hypomethylating agents, G-CSF, hydroxyurea or lenalidomide. Dynamics of Hb, ANC, and PLT were studied by deriving linear models of each variable for each pt. Only pts with ≥3 measures of Hb, ANC and PLT and with stable or worsening corresponding cytopenia (model slope ≤0) were considered in each analysis, regardless of the goodness of fit (R2) of models. Time (T) to lose 1 g/dL of Hb (THb), 1.0 x109/L of ANC (TANC) and 50 x109/L of PLT (TPLT) were derived with the formula: T ∼ 1/slope. All survival analyses were made from the date of registry entry to last follow-up, death, or progression to AML. Unless specified, survival analyses were Cox models using continuous variables accounting for interactions. Results: 530 pts met study inclusion criteria (M/F: 314/216, median age: 73y). WHO diagnosis was 5q- syndrome, RA, RARS, RCMD, RCMD-RS, RAEB-1 and MDS-U in 5, 21, 20, 38, 7, 8 and 2% respectively (resp). IPSS risk was low, int-1 and low/int-1 (cytogenetics not available) in 55%, 38% and 7% resp. At registry entry, median Hb, ANC and PLT were 10.4 g/dL, 2.4 x109/L and 187 x109/L resp. and 23% were RBC transfusion-dependent; 293 received an ESA. The median number of available blood counts was 4 (range 3–9). THb, TANC and TPLT could be determined because of a stable or worsening cytopenia (slope ≤0) in 250/508, 258/495 and 301/509 pts with ≥3 values. There was no significant correlation between the number of values available and the goodness-of-fit (R2) of linear models (all P>0.3). Median THb TANC and TPLT were 23.5 (interquartile range [IQR]: 42.2), 28.7 (IQR: 52.1) and 26.9 (IQR: 49.2) months respectively. Because these figures are derived from linear models, they can be simply rescaled by a proportional extrapolation for daily practice (eg. −1 x109/L ANC at 28.7 months = −0.41 x109/L [12/28.7] at 12 months). THb, TANC and TPLT were not correlated to age, cytogenetic risk, IPSS, IPSS-R or baseline simplified WPSS (Malcovati. Haematologica 2011; all P>0.2). TANC and TPLT (but not THb) were shorter in pts with baseline RBC transfusion dependence (P=.02 and .003, resp.). With a median follow-up of 20.9 months in the 530 pts, 19 patients have progressed (AML: 14, RAEB: 5) and 71 patients have died; 3-year estimates of overall (OS) and progression-free (PFS) survivals were 74.4% and 73.6%. All further analyses are shown for OS and give similar results for PFS. In univariate analysis, longer TANC (hazard ratio [HR] for 6-months increments: 0.88 [95% CI: 0.80–0.97], P=.008) and TPLT (HR: 0.01 [95% CI: 0.001–0.30], P=.007) but not THb (P=.07) were associated with prolonged OS. Pts with a ≥1 x109/L decrease in ANC in less than the median time of 28.7 months (N=129) had a 3-year OS of 66.3% [95% CI: 55.0–79.9%] vs 89.3% [79.7–100%]. Pts with a ≥50 x109/L decrease in PLT in less than the median of 26.9 months (N=151) had a 3-year OS of 59.4% [46.8–75.4%] vs 85.6% [77.5–94.6%] (Figure, both P<10−4). There was no significant difference in the cause of death between those subgroups. In multivariate analysis, the prognostic impact of TANC and TPLT remained independent of baseline IPSS (P=.006 and P=.01 resp.) or IPSS-R (both P=.01), and of simplified time-dependent WPSS (P=.004 and P=.03). A landmark analysis at 2 years, using only retrospective data to derive TANC and TPLT is planned. Conclusion: In lower-risk MDS with stable or worsening cytopenias, kinetics of decline can be approximated to be linear to allow easy prognostic use in clinical practice. Faster decline of ANC and to a lesser extent of PLT counts, but not of Hb level (possibly because of transfusions and use of ESA), is associated with shorter OS and PFS, independently of IPSS, IPSS-R and WPSS. Disclosures: Germing: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Imetelstat Treatment Leads to Durable Transfusion Independence (TI) in RBC Transfusion-Dependent (TD), Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Who Are Lenalidomide (LEN) and HMA Naive

Blood ◽

10.1182/blood-2018-99-114877 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 463-463 ◽

Cited By ~ 5

Author(s):

David P. Steensma ◽

Uwe Platzbecker ◽

Koen Van Eygen ◽

Azra Raza ◽

Valeria Santini ◽

...

Keyword(s):

Board Of Directors ◽

Lower Risk ◽

Research Funding ◽

Employment Equity ◽

Advisory Committees ◽

Transfusion Independence ◽

Equity Ownership ◽

Grade 3 ◽

Rbc Transfusion

Abstract BACKGROUND: Patients with TD lower-risk (LR)-MDS relapsed or refractory to ESA have limited treatment options. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere lengths and active telomerase, characteristics observed in some MDS patients. IMerge is an ongoing global study of imetelstat in RBC TD patients with LR-MDS (IPSS Low or Int-1). In the first 32 patients enrolled, 8-week TI rate was 34%, with 24-week TI of 16%, and HI-E of 59%. The most frequently reported adverse events were reversible grade ≥3 cytopenias (Fenaux et al EHA 2018 Abstr S1157). Higher response rates were observed in patients (n=13) who were LEN and HMA naïve without del(5q). We report here results in an additional 25 LEN and HMA naïve patients without del(5q), with longer term follow-up of the 13 initial patients meeting the same criteria. METHODS: IMerge is a phase 2/3 trial (NCT02598661) that includes LR-MDS patients with a high transfusion burden (≥4 units / 8 weeks) who are relapsed/refractory to ESA or have sEPO >500 mU/mL. The additional 25 were required to be LEN and HMA naïve and lack del(5q). Imetelstat 7.5 mg/kg was administered IV every 4 weeks. In addition to the key endpoints noted above, secondary endpoints include safety, time to and duration of TI. Biomarkers are also being explored, including telomerase activity, hTERT, telomere length, and genetic mutations. RESULTS: Overall, for the 38 LEN/HMA naïve and non-del(5q) patients, median age was 71.5 years and 66% were men. 63% of patients were IPSS Low and 37% Int-1. Median prior RBC transfusion burden was 8.0 (range 4-14) U, and 71% had WHO 2008 RARS or RCMD-RS. 9/37 (24%) patients with evaluable sEPO levels had baseline level >500 mU/mL. As of July 2018, with a median follow-up of 25.8 months for the initial 13 patients, and 5.2 months for the 25 recently included patients, the 8-week RBC-TI rate was 37% (14/38). Durability of 24-week TI responses was demonstrated, with a median duration of 10 months and the longest ongoing response now >2 years. Among the patients achieving durable TI, all showed a Hb rise of ≥3.0 g/dL compared to baseline during the transfusion-free interval. Response rates were similar in RARS/RCMD-RS (33% [9/27]) and other patients (27% [3/11]), and those with baseline EPO levels >500 mU/mL (33% [3/9]) and ≤500 mU/mL (32% [9/28]). Reversible grade ≥3 neutropenia and thrombocytopenia were each reported in 58% of the patients. Liver function test (LFT) elevations were mostly grade 1/2. Reversible grade 3 LFTelevations were observed in 3 (8%) patients on study. An independent Hepatic Review Committee deemed the observed LFT elevations were not imetelstat-related hepatic toxicities. SUMMARY / CONCLUSIONS: In this cohort of 38 non-del(5q) LR-MDS patients with a high RBC transfusion burden who were ESA relapsed/refractory and naïve to LEN/HMA, single-agent imetelstat yielded a TI rate of 37%, with a median duration of 10 months and limited side effects. Durable responses were characterized by transfusion independence >24 weeks and accompanied by Hb rise. Updated data will be presented. Disclosures Steensma: Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy. Platzbecker:Celgene: Research Funding. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Raza:Kura Oncology: Research Funding; Onconova: Research Funding, Speakers Bureau; Celgene: Research Funding; Novartis: Speakers Bureau; Geoptix: Speakers Bureau; Janssen: Research Funding; Syros: Research Funding. Santini:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding. Germing:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding. Font:Celgene: Membership on an entity's Board of Directors or advisory committees. Samarina:Janssen: Research Funding. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bussolari:Janssen: Employment, Equity Ownership. Sherman:Janssen: Employment, Equity Ownership. Sun:Janssen: Employment, Equity Ownership. Varsos:Janssen: Employment, Equity Ownership. Rose:Janssen: Employment, Equity Ownership. Fenaux:Roche: Honoraria; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

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How Are Patients (Pts) with Lower-Risk Myelodysplastic Syndromes (MDS) Treated? Impact on Clinical Evolution and Overall Survival: A Report from the Erasme Study

Blood ◽

10.1182/blood.v126.23.5239.5239 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5239-5239

Author(s):

Julia Montoro ◽

Helena Pomares ◽

Itziar Oiartzabal ◽

Teresa Bernal ◽

Edgardo Barranco ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Board Of Directors ◽

Median Time ◽

Lower Risk ◽

Low Risk ◽

Advisory Committees ◽

Very High ◽

Rbc Transfusion

Abstract Introduction: As MDS includes a wide range of heterogeneous neoplastic disorders, the therapeutic approaches for treatment of MDS vary greatly. The aim of this study was to evaluate the use of different therapies, and assess time from diagnosis to therapy initiation and pt outcomes, in an unselected Spanish population with MDS from the ERASME study. Methods : The ERASME study (CEL-SMD-2012-01) is an observational, prospective, multicenter study of pts with either MDS or chronic myelomonocytic leukemia (CMML); disease was defined using the 2008 World Health Organization (WHO) classification system. Initial pt management strategy was classified into 3 groups: active therapy (AT), such as chemotherapy and treatment with azacitidine (AZA); allogeneic hematopoietic cell transplantation (HCT), which included pts receiving other therapies before transplantation; and observation and support (OB&SP), which included red blood cell (RBC) and platelet transfusions, and growth factors. Here, we present overall survival (OS) data from a prespecified interim analysis of pts with International Prognostic Scoring System (IPSS)-defined Low- and Intermediate-1-risk (lower-risk [LR]) MDS using the Kaplan-Meiermethod. Results : A total of 207 IPSS-defined LR MDS pts (117 with Low-risk and 81 with Intermediate-1-risk MDS) were recruited from Jan 2013 to Feb 2014; median follow-up was 16.1 months (interquartile range [IQR] 11.5-19.1). Pt characteristics are described in the Table. We identified 14 pts with high-risk features (HRF) for MDS based on the presence of ≥ 1 of the following: neutropenia (n = 6; absolute neutrophil count < 0.5 × 109/L); thrombocytopenia (n = 4; platelet count < 50 × 109/L); grade 2-3 bone marrow fibrosis (n = 1); or adverse cytogenetic risk (n = 3). At baseline, 28 (14%) pts had RBC transfusion-dependence (RBC-TD), 166 (80%) were RBC transfusion-independent (RBC-TI), and 13 (6%) had missing data. Probability of RBC-TD increased over time with 41 of 166 pts having RBC-TD after 12 months. Median OS of RBC-TD versus RBC-TI pts was not reached (NR) (95% confidence interval [CI] 19.65 months-NR) versus NR (95% CI 22.93 months-NR), respectively (hazard ratio [HR] 3.2, 95% CI 1.13-9.22; P = 0.0275). At diagnosis, 117 (57%) pts (including 4 with HRF) were considered for OB, and 76 (37%) pts for SP (69 pts [5 HRF] for erythropoiesis-stimulating agents, and 7 pts [3 HRF] for RBC and platelet transfusions). Only 10 (5%) pts were considered for AT, which included AZA (n = 5; 1 HRF), lenalidomide (n = 4; 1 HRF), and alemtuzumab (n = 1). HCT was considered in 4 pts (2%; 3 with prior AZA treatment and 1 with prior chemotherapy). After 12 months, 13 (11%) of 117 OB pts switched to AT; median time to AT was 30 weeks (IQR 24.0-44.0). Of 76 pts receiving SP, 23 (30%) switched to AT; median time to AT was 23.9 weeks (IQR 16.3-39.1). Of 184 pts with Revised-IPSS (IPSS-R) scores, at 12 months' follow-up 35 had died (15 of 140 Very Low/Low-risk pts, 15 of 32 Intermediate-risk pts, and 5 of 12 High/Very High-risk pts). At 12 months, 36 of 207 (17%) LR MDS pts had died, including 6 of the 14 HRF pts. Median OS was shorter among HRF pts versus non-HRF pts (19.45 months [95% CI 5.52-NR] vs NR [95% CI NR-NR], respectively) (HR 3.5, 95% CI 1.47-8.53; P = 0.0048). Median OS for IPSS-R Very Low/Low-risk and Intermediate/High/Very High-risk pts was NR (95% CI NR-NR) and 19.45 months (95% CI 11.99-NR), respectively (HR 5.4, 95% CI 2.8-10.7; P < 0.001). Conclusions : The typical treatment of LR MDS pts in Spain consists mainly of supportive care. We observed that risk of RBC-TD increased after diagnosis. These data suggest more attention should be provided at diagnosis or during follow-up of LR MDS pts with poor prognosis, and that they should be considered for more intensive treatment. Abstract presented on behalf of the ERASME Study Investigators Group. Disclosures Off Label Use: Azacitidine was used in IPSS Intermediate-1-risk patients with MDS, and lenalidomide was used in MDS patients with del(5q) plus > 1 cytogenetic abnormality. Castellanos:SCLHH: Other: Membership; SEHH: Other: Membership. Navarro:Celgene Corporation: Employment. López:Celgene SL Unipersonal: Employment, Equity Ownership, Honoraria. Valcárcel:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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111. Duration of Antibiotic Therapy after Debridement and Implant Retention in Patients with Periprosthetic Joint Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.111 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S68-S69

Author(s):

Don Bambino Geno Tai ◽

Elie Berbari ◽

Matthew P Abdel ◽

Brian Lahr ◽

Aaron J Tande

Keyword(s):

Lower Risk ◽

Time Dependent ◽

Oral Antibiotic ◽

Material Support ◽

Joint Infections ◽

Optimal Duration ◽

Implant Retention ◽

Antibiotic Duration ◽

Time Dependent Analysis

Abstract Background Debridement, antibiotics, and implant retention (DAIR) is appropriate for select acute postoperative and hematogenous periprosthetic joint infections (PJIs). However, the optimal duration of antimicrobial therapy in patients treated with DAIR has not been defined. Therefore, we aimed to identify the ideal duration of parenteral and oral antibiotics after DAIR. Methods We performed a retrospective study of patients >18 years of age with hip or knee PJI managed with DAIR between January 1, 2008, and December 31, 2018, at Mayo Clinic. PJI was defined using criteria adapted from the International Consensus Meeting on PJI. The outcome was defined as either PJI recurrence or unplanned reoperation due to infection. Joint-stratified Cox proportional hazards regression models with time-dependent covariates were used to assess nonlinear effects of antibiotic duration. Hazard ratios were computed based on prespecified time points for comparison, whereas p-values represented the overall effect across the entire range of durations. Results There were 247 unique episodes of PJI in 237 patients during the study period. Parenteral antibiotics were given in 99.2% of cases (n=245). This was followed by chronic oral antibiotic suppression in 92.2% (n=226) with a median duration of 2.2 years (1.0-4.1). DAIR failed in 65 cases over a median follow-up of 4.4 years, with a 5-year cumulative incidence of 28.1%. After adjustment for risk factors, there was no significant association between duration of parenteral antibiotics and treatment failure (p=0.203), with no difference between four versus six weeks (HR 1.11; 95% CI 0.71-1.75) (Figure 1). However, both use and longer duration of oral antibiotic therapy was associated with a lower risk of failure (p=0.006). To account for the possibility that this association was driven by results during early follow-up, conditional analyses at one- and two-year follow-up were performed. Both showed a significantly lower risk for a longer duration of antibiotics (Figure 2). Figure 1. Time-Dependent Analysis of Parenteral Antibiotic Duration Figure 2. Time-Dependent Analysis of Oral Antibiotic Suppression Duration Conclusion After DAIR, efficacy from four weeks of parenteral antibiotics was no different from six weeks when followed by chronic oral antibiotic suppression. Our results could not establish an optimal duration but suggested that continuing suppression portends a lower risk of failure of DAIR. Disclosures Elie Berbari, MD, Uptodate.com (Other Financial or Material Support, Honorary unrelated to this work) Matthew P. Abdel, MD, Stryker and AAOS Board of Directors (Board Member, Other Financial or Material Support, Royalties) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing)

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Impact of Red Blood Cell Transfusion Burden Status in Patients with Lower-Risk Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2019-127486 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3013-3013

Author(s):

Montserrat Arnan Sangerman ◽

Helena Pomares ◽

Esther Alonso ◽

Javier Grau ◽

Mercedes Galiano ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Progression Free Survival ◽

Low Risk ◽

Age At Diagnosis ◽

Free Survival ◽

The Impact ◽

Rbc Transfusion

Background: RBC-transfusion dependency (RBC-TD) is associated with a decreased probability of overall survival (OS) and progression free survival (PFS) in patients with myelodysplastic syndromes (MDS) (Malcovati L et al. J Clin Oncol 2007 25:3505) but it is unclear if transfusion dose burden is an independent prognostic factor. The purpose of this study was to assess the impact on lower-risk MDS patients, of RBC-transfusion (RBCT) burden status defined according to revised 2018 IWG criteria (Platzbecker et al; Blood 2018). Material and Methods: According to the R-IPSS selection criteria, we identified in our database 474 lower-risk (R-IPSS risk very low, low and intermediate) MDS patients diagnosed at the Catalan Institute of Oncology of Barcelona (01/1992-07/2018). Transfusion burden history was prospectively registered in our database. Data on the transfusion burden was calculated dividing the cumulative total of units of blood received at the end by the time since the beginning of the interval in which the first transfusion was received. RBCT burden, defined according to 2018 IWG criteria, divided patients into 3 categories (non-transfused [NTD], low transfusion burden [LTB] (3 to 7 units in 16 weeks) and high transfusion burden [HTB] patients (³ 8 units in 16 weeks). In this analysis, patients who had received 1 or 2 RBC units in 16 weeks, where included in the NTD category. Overall survival (OS) and progression free survival (PFS) were measured in years since diagnosis. Results: Median age at diagnosis was 72 years (range 32-101). 332 (70%) patients were male. WHO diagnosis was: 3% CRDU, 7% RA, 42% RCMD, 14% RAEB-1, 4% RAEB-2, 26% CMML, the remaining 4% were MDS-U and isolated 5q deletion. R-IPSS categories were: 178 (38%) very low risk, 219 (46.2%) low risk and 77 (16%) intermediate risk. Median follow up time for survivors was 5.4 years (range 0.25-23.8). 132 (28%) of patients were transfusion dependents (LTB and HTB patients). Mean dose density of packed red blood cells amongst those who were transfusion dependents was 3.2 units per month, with a median of 2.9 units per month (IQR 1.9-4.3). At the time of last follow up, 274 (58%) patients had died and 72 (15%) had progressed to AML. According to 2018 IWG criteria, RBCT burden categories were 342 (72%) NTD, 35 (7%) LTB and 97 (21%) HTB patients. Median OS for RBCT burden categories: NTD (8 years; 95% CI 6.6-9.5), LTB (6.2 years; 95% CI 4.2-8.1) and HTB (3.1 years; 95% CI 2.4-3.8) were significantly different (p<0.001; Figure 1). Moreover, the rate of progression to acute myeloid leukemia was 39 (11%), 7 (20%) and 26 (27%) for categories NTD, LTB and HTB respectively (p<0.001). Multivariate analysis performed included gender, age at diagnosis, IPSS-R and RBCT burden status and showed that RBCT burden status was associated with poor OS and PFS, independent of R-IPSS category, age and gender (Table 1). Transfusion burden was inversely associated with OS and PFS with an increasing effect on hazard ratio. Conclusions: Our results confirm in our single-centre experience the negative impact on survival and progression-free survival of RBCT treatment, even at relatively low dose burden. As therapeutical decisions are based on the initial prognostic risk assessment, the inclusion of RBCT burden categories may provide more precise prognostic information with impact on the therapeutic approach. Disclosures Sureda: Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Roche: Honoraria; BMS: Consultancy, Honoraria; Gilead: Consultancy; Janssen: Consultancy, Honoraria.

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

Journal of Neurosurgery ◽

10.3171/2019.3.jns183500 ◽

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.

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Spectrocoulometry – a new spectro-electrochemical technique

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19871386 ◽

1987 ◽

Vol 52 (6) ◽

pp. 1386-1396 ◽

Cited By ~ 3

Author(s):

Ján Mocák ◽

Michal Németh ◽

Mieczyslaw Lapkowski ◽

Jerzy W. Strojek

Keyword(s):

Optical Probe ◽

Optical Signal ◽

Open Circuit ◽

Electrochemical Technique ◽

Kinetics Of Oxidation ◽

Hydrolytic Reaction ◽

Experimental Errors ◽

Mechanism And Kinetics ◽

Kinetics Of

A spectrocoulometric macrocell with a direct-view optical probe was designed and constructed, where the optical signal is transferred by light-conducting glass or quartz fibres permitting to work at wavelengths above 410 or 300 nm. The method of measurement on the proposed equipment is described; it was tested in the study of the mechanism and kinetics of oxidation of Fe(bipy)32+ ions (bipy = 2,2'-bipyridyl) with the use of potentiostatic coulometric electrolysis with open-circuit relaxation at a suitable time. The primary product of electrolysis, Fe(bipy)33+, undergoes a follow-up hydrolytic reaction with the formation of a binuclear complex. The rate constant of the reaction of the first order involves the contributions, kBi, from all bases present in solution; the corresponding values for H2O, OH-, bipy, and CH3COO- ions at a ionic strength 0·5 mol dm-3 and 25 °C were determined as kOH = (5·0 ± 0·6) . 105 mol-1 dm3 s-1, kbipy = (1·3 ± 0·2) . 10-1 mol-1 dm3 s-1, kAc = (5·8 ± 1·0) . 10-2 mol-1 dm3 s-1, and kH2O is not significant with respect to experimental errors.

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Long-term risk of primary liver cancers in entecavir versus tenofovir treatment for chronic hepatitis B

Scientific Reports ◽

10.1038/s41598-020-80523-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Te-Sheng Chang ◽

Yao-Hsu Yang ◽

Wei-Ming Chen ◽

Chien-Heng Shen ◽

Shui-Yi Tung ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Lower Risk ◽

Entire Population ◽

Liver Cancers ◽

Cirrhotic Patients ◽

Registry Database

AbstractIt remains controversial whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) is associated with different clinical outcomes for chronic hepatitis B (CHB). This study aimed to compare the long-term risk of ETV versus TDF on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in CHB patients from a large multi-institutional database in Taiwan. From 2011 to 2018, a total of 21,222 CHB patients receiving ETV or TDF were screened for eligibility. Patients with coinfection, preexisting cancer and less than 6 months of follow-up were excluded. Finally, 7248 patients (5348 and 1900 in the ETV and TDF groups, respectively) were linked to the National Cancer Registry database for the development of HCC or ICC. Propensity score matching (PSM) (2:1) analysis was used to adjust for baseline differences. The HCC incidence between two groups was not different in the entire population (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.66–1.02, p = 0.078) and in the PSM population (HR 0.83; 95% CI 0.65–1.06, p = 0.129). Among decompensated cirrhotic patients, a lower risk of HCC was observed in TDF group than in ETV group (HR 0.54; 95% CI 0.30–0.98, p = 0.043, PSM model). There were no differences between ETV and TDF groups in the ICC incidence (HR 1.84; 95% CI 0.54–6.29, p = 0.330 in the entire population and HR 1.04; 95% CI 0.31–3.52, p = 0.954 in the PSM population, respectively). In conclusion, treatment with ETV and TDF showed a comparable long-term risk of HCC and ICC in CHB patients.

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A comparison of zero-inflated and hurdle models for modeling zero-inflated count data

Journal of Statistical Distributions and Applications ◽

10.1186/s40488-021-00121-4 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Cindy Xin Feng

Keyword(s):

Health Services ◽

Count Data ◽

Goodness Of Fit ◽

Negative Binomial ◽

Simulation Studies ◽

Final Choice ◽

Hurdle Models ◽

Count Distribution ◽

Careful Assessment

AbstractCounts data with excessive zeros are frequently encountered in practice. For example, the number of health services visits often includes many zeros representing the patients with no utilization during a follow-up time. A common feature of this type of data is that the count measure tends to have excessive zero beyond a common count distribution can accommodate, such as Poisson or negative binomial. Zero-inflated or hurdle models are often used to fit such data. Despite the increasing popularity of ZI and hurdle models, there is still a lack of investigation of the fundamental differences between these two types of models. In this article, we reviewed the zero-inflated and hurdle models and highlighted their differences in terms of their data generating processes. We also conducted simulation studies to evaluate the performances of both types of models. The final choice of regression model should be made after a careful assessment of goodness of fit and should be tailored to a particular data in question.

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Lower Risk for Dementia Following Adult Tetanus, Diphtheria and Pertussis (Tdap) Vaccination

The Journals of Gerontology Series A ◽

10.1093/gerona/glab115 ◽

2021 ◽

Author(s):

Jeffrey F Scherrer ◽

Joanne Salas ◽

Timothy L Wiemken ◽

Christine Jacobs ◽

John E Morley ◽

...

Keyword(s):

Lower Risk ◽

Protective Effects ◽

Proportional Hazard ◽

Veterans Health ◽

Cox Proportional Hazard ◽

Dementia Risk ◽

Incident Dementia ◽

Nonspecific Effects ◽

Reduce Risk

Abstract Background Adult vaccinations may reduce risk for dementia. However it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia. Methods Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were ≥65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of two index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and in age sub-groups (65-69, 70-74, ≥75 years of age). Results VHA patients were, on average, 75.6 (SD±7.5) years of age, 4% female, and 91.2% were white race. MarketScan patients were 69.8 (SD±5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without Tdap vaccination, had a significantly lower risk for dementia in both cohorts (VHA: HR=0.58; 95%CI:0.54 - 0.63 and MarketScan: HR=0.58; 95%CI:0.48 - 0.70). Conclusions Tdap vaccination was associated with a 42% lower dementia risk in two cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.

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Improved risk estimation of locoregional recurrence, secondary contralateral tumors and distant metastases in early breast cancer: the INFLUENCE 2.0 model

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06335-z ◽

2021 ◽

Author(s):

Vinzenz Völkel ◽

Tom A. Hueting ◽

Teresa Draeger ◽

Marissa C. van Maaren ◽

Linda de Munck ◽

...

Keyword(s):

Breast Cancer ◽

Locoregional Recurrence ◽

Clinical Decision Making ◽

Metastatic Breast ◽

Distant Metastases ◽

Time Dependent ◽

Individual Risk ◽

Primary Tumors ◽

Statistical Approaches

Abstract Purpose To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. Methods Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. Results Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. Conclusions INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.

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