treatment intensity
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2021 ◽  
Author(s):  
Jove Graham ◽  
Tonia Novosat ◽  
Haiyan Sun ◽  
Brian J. Piper ◽  
Joseph A. Boscarino ◽  
...  

Abstract BackgroundOsteoarthritis (OA) is a complex disease, and prior studies have documented the health and economic burdens of patients with OA compared to those without OA. Our goal was to use two strategies to further stratify OA patients based on both pain and treatment intensity to examine healthcare utilization and costs using electronic records from 2001-2018 at a large integrated health system. Methods Adult patients with ≥1 pain numerical rating score (NRS) and diagnosis of OA were included. Pain episodes of ≥90 days were defined as mild (0-3), moderate (4-6) or severe (7-10) based on initial NRS. Patients were initially classified as mild and moved to moderate-severe OA if any of eight treatment-based criteria were met. Outpatient visits (OP), emergency department visits (ED), inpatient days, and healthcare costs (both all-cause and OA-specific) were compared among pain levels and OA severity levels as frequencies and per-member-per-year rates, using generalized linear regression models adjusting for age, sex and body mass index, with contrasts of p<0.05 considered significant. ResultsWe identified 127,656 patients, 92,576 with pain scores. Moderate and severe pain were associated with significantly higher rates of OA-related utilization and costs, and all-cause ED visits and pharmacy costs. Moderate-severe OA patients had significantly higher OA-related utilization and costs, and all-cause OP, ED and pharmacy costs. ConclusionsPain and treatment intensity were both strongly associated with OA-related resource utilization but not consistently with all-cause utilization. With better understanding of how OA patients intensify services, thus increasing costs, we can deploy targeted preventative strategies aimed at halting progression into more costly phases of the disease.


2021 ◽  
Vol 159 ◽  
pp. 194-204
Author(s):  
Paolo Bossi ◽  
Annalisa Trama ◽  
Alice Bernasconi ◽  
Salvatore Grisanti ◽  
Issa Mohamad ◽  
...  

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi10-vi10
Author(s):  
Shigeru Yamaguchi ◽  
Yukitomo Ishi ◽  
Michinari Okamoto ◽  
Ryousuke Sawaya ◽  
Hiroaki Motegi ◽  
...  

Abstract Background: WHO grade 2 and 3 adult gliomas are nowadays getting together as lower-grade gliomas (LrGGs), but we had been recognized grade 3 (G3) tumors as high-grade and grade 2 (G2) tumors as low-grade. In this report, we investigate the treatment and prognosis of the patients with LrGG harboring IDH mutations in our institutions. Methods:We retrospectively review primary treatments and their prognosis for LrGG patients with IDH mutation since 2003. They categorized as astrocytomas and oligodendrogliomas according to 1p/19q loss-of-heterozygosity status. Prognosis were evaluated by overall survival. Postoperative primary treatments applied chemo-radiotherapy (CRT), radiotherapy only (RT), chemotherapy only (CT), and observation (Ob). Results: 36 astrocytomas and 60 oligodendrogliomas were identified. In astrocytomas, the patients with G3 (N=16) were treated by CRT (N=14) or CT (N=2), and the patients with G2 (N=20) were treated by CRT (N=2), RT (N=3), CT (N=3), or Ob (N=12). In oligodendrogliomas, the patients with G3 (N=34) were treated by CRT (N=32) or CT (N=2), and the patients with G2 (N=26) were treated by CRT (N=3), RT (N=1), CT (N=5), or Ob (N=17). 10-year survival rate (10yOS) of astrocytomas and oligodendrogliomas are 54% and 90%, respectively (p=0.002). According to histological malignancy, 10yOS of G3 and G2 astrocytomas were 54% and 54%, respectively (p=0.97) and that of G3 and G2 oligodendrogliomas were 86% and 100%, respectively (p=0.64). In both group, there are no different of prognosis according to histological malignancy. Discussion: There was no prognostic different between G2 and G3 astrocytomas in our institution. Since the treatment intensity for G2 and G3 astrocytomas were clearly different, the primary treatment for G2 astrocytomas might be insufficient. On the other hand, there were no prognostic different between G2 and G3 oligodendrogliomas in our institution, as with recent reports, so the primary treatment intensity for oligodendrogliomas should be appropriate.


2021 ◽  
pp. 026565902110351
Author(s):  
Sabine Leonhartsberger ◽  
Eva Huber ◽  
German Brandstötter ◽  
Ruth Stoeckel ◽  
Becky Baas ◽  
...  

Motor learning principles guide treatment of childhood apraxia of speech (CAS). Previous studies found children to benefit from higher-intensity conditions; however, they did not control for the total amount of therapy time. The aims of the article are to examine the effects of high versus low treatment frequency in intervention for CAS in German-speaking children. An alternating single-subject design with multiple baselines was applied to compare frequent, short sessions with fewer, longer sessions in terms of speech production accuracy in four children with CAS while keeping the total therapy time constant. We administered a version of integral stimulation treatment. Despite inter-individual differences, changes under both treatment conditions showed similar positive trajectories for all four children. Untreated control targets also improved across participants and conditions. Maintenance and generalization to untreated targets were observed two weeks and three months post treatment, independent of treatment intensity. Our results show no significant advantage of more intensive treatment when the total therapy time is held constant. This study contributes to the evidence base for the use of integral stimulation in treating children with CAS, and in particular those who speak languages other than English.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Motoshi Iwao ◽  
Ryota Tanaka ◽  
Yosuke Suzuki ◽  
Takeshi Nakata ◽  
Kohei Aoki ◽  
...  

AbstractResponse to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r =  − 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4125-4125
Author(s):  
Kieran D Sahasrabudhe ◽  
Melanie T Rebechi ◽  
Ying Huang ◽  
Greg K. Behbehani ◽  
Bhavana Bhatnagar ◽  
...  

Abstract Introduction The FDA has recently approved several oral targeted therapies for Acute Myeloid Leukemia (AML). These therapies have been approved in patients with relapsed/refractory disease and as frontline therapy in patients ineligible for intensive induction chemotherapy. These agents are also being increasingly utilized as frontline therapy in patients of all ages and fitness levels on clinical trials and through off label prescribing. The decision to use intensive chemotherapy vs targeted therapy is particularly relevant in patients aged 60-75 due to the heterogeneous nature of this population with respect to disease characteristics, performance status, and comorbidities. However, the relative survival impact of intensive chemotherapy vs targeted therapy in this patient population has not been extensively studied. We conducted a retrospective analysis to compare survival outcomes of these treatment approaches and to determine the relative impact of treatment intensity compared to other variables that are known to affect survival in AML patients. Methods In this single-center, retrospective study, patients aged 60-75 diagnosed with AML from 2016-2020 were included if they received treatment with high intensity chemotherapy (HiC), low intensity targeted therapy (LITT), or both during the course of treatment and prior to transplant. HiC was defined as a regimen containing cytarabine + an anthracycline given on a "7+3" based schedule. Patients treated with liposomal cytarabine-daunorubicin were excluded. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or in combination with a hypomethylating agent. Between-group analysis was conducted for patients who had received HiC at any point during treatment (any HiC) vs patients who had not (LITT only). Overall Survival (OS) was analyzed by Kaplan-Meier method with log-rank test used for between-group comparisons. Cox regression model was used to associate risk factors with OS. Univariable models were first fit, then a multivariable model was built using backward selection. Transplant status was included as a time-dependent variable. Results A total of 141 patients were included, 80 received any HiC and 61 received LITT only. Compared with the any HiC group, patients in the LITT only group demonstrated older age, a higher percentage of secondary AML, a lower percentage of FLT3 ITD mutations, a higher percentage of IDH1 and IDH2 mutations, a lower white blood cell count, and a trend toward higher ELN risk classification at baseline (Table 1). Median OS was significantly longer in the any HiC group (21.8 months vs 13.6 months). A significantly higher percentage of patients receiving any HiC underwent allogeneic stem cell transplantation, but post-transplant OS was not significantly different between the two groups (Table 2). On univariable analysis, receipt of HiC, lower ELN risk classification, and receipt of transplant were all significantly associated with superior OS. Age, performance status, secondary AML, and white blood cell count at diagnosis notably did not have a significant association with OS in this cohort. On multivariable analysis, treatment intensity was no longer found to have an independently significant impact on survival after accounting for ELN risk (hazard ratio (HR) for unfavorable 3.02, p&lt;0.01) and receipt of transplant (HR 0.25, p&lt;0.01) (Table 3). Discussion The results of this study show that baseline disease characteristics and receipt of transplant were the most important predictors of survival in this cohort of AML patients aged 60-75. These factors were notably more impactful than treatment intensity and chronological age. These findings support the use of transplant in this patient population regardless of treatment intensity, especially in those with higher risk disease. Limiting factors in this study include the retrospective design and relatively small sample size. Ultimately, larger trials with more patients will be needed to confirm these findings including prospective, randomized trials comparing intensive chemotherapy to lower intensity targeted therapy in patients who are transplant-eligible at baseline. Figure 1 Figure 1. Disclosures Bhatnagar: Novartis: Honoraria; Pfizer: Honoraria; Kite: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Astellas: Honoraria; Cell Therapeutics: Honoraria, Research Funding. Blachly: INNATE: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; KITE: Consultancy, Honoraria. Borate: Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Mims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Vasu: Seattle Genetics: Other: travel support; Boehringer Ingelheim: Other: Travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Walker: Novartis: Other: clinical trial support; Geron: Other: clinical trial support; Newave: Other: clinical trial support.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1222-1222
Author(s):  
Monika Adamska ◽  
Ewelina Kowal-Wisniewska ◽  
Marta Baranska ◽  
Anna Przybylowicz-Chalecka ◽  
Anna Lojko-Dankowska ◽  
...  

Abstract Background: Therapy-related acute myeloid leukemia (t-AML) represents emerging challenge of the modern oncology as a life-threatening complication of cytotoxic therapy. Disease characterises poor prognosis and presence of adverse cytogenetic and genetic abnormalities. The goal of the study: Clinical outcome of t-AML patients with respect to genetic changes and treatment intensity. Patients and methods: Retrospective analysis of all consecutive AML patients treated in years 2000-2021 in one hematological center was performed. Diagnosis of t-AML was established according to WHO 2016 criteria. Overall survival (OS) and progression free survival (PFS) was defined to evaluate treatment outcomes only within t-AML patients undergoing intensive treatment (standard induction/consolidation; allogeneic cell transplantation (alloHCT) if eligible). Results: Among 743 AML patients 60 (8.1%) were diagnosed as t-AML (38 woman) with median age 57 years. Solid tumors (ST) preceded t-AML in 63.3%, hematological neoplasms (HN) in 36.7%. Majority of t-AML was preceded by breast cancer (30.0%), Hodgkin Lymphoma (11.7%), non-Hodgkin Lymphoma (10.0%) and ovarian cancer (10.0%). Median latency time for ST and HN subgroups was 5 vs 7 years respectively (P = .036). Previous cytotoxic therapy consisted of chemotherapy, radiotherapy or combination in 56.6%, 18.3% and 25.0% (autologous cell transplantation was performed in 54.5% of HN). Cytogenetic and molecular biology analysis was performed in 44 and 27 of t-AML respectively. Cytogenetic abnormalities, complex karyotype and normal karyotype occurred in 78.9%, 28.9% and 15.8% patients. KMT2A, RUNX1-RUNX1T1 and PML-RARA rearrangement was found in 21.1%, 18.4% and 7.9% of t-AML. FLT3-ITD, FLT-TKD, NPM1 and C-KIT DNA sequence variant occurred as follows: 14.8%, 7.4%, 3.7% and 3.7% correspondingly. Three pathogenic TP53 DNA sequence variants were detected in t-AML patients: c.711G&gt;A, c.704A&gt;G and c.989T&gt;C (analysis performed on 20 t-AML patients). According ELN2017 genetic risk stratification patients were classified as adverse, intermediate and favorable in 51.4%, 35.1% and 13.5% respectively. Intensive treatment was implemented in 48 patients including alloHCT in 23 of them. Median OS and PFS was 15 and 8 months respectively for whole treated group. Median OS in t-AML undergoing intensive chemotherapy only vs alloHCT was 7 vs 47 months (P = .0025) with 12-year OS after alloHCT- 21.1% (Fig.1A). Among therapy-related acute promyelocytic leukemia (t-APL) patients median OS was not reached, without alloHCT. Median OS was higher for t-AML patients younger than 65 years than older ones: 20 vs 13 months respectively (P = .048) (Fig.1B). Among t-AML median OS in subgroup with adverse ELN 2017 vs intermediate and favorable ELN 2017 was 15 vs 40 months (P = .037) with 5-years OS 8.2% vs 41.0% (Fig.1C). In multivariate Cox proportional hazard regression model alloHCT was the only factor significantly influencing OS (HR = 0.16, 95% CI = 0.05-0.56, P = .004). All patients with TP53 mutations were intensively treated, one patient underwent alloHCT. 66.6% of patients had complex karyotype and any co-occuring DNA sequence variant was detected. Importantly, c.704A&gt;G and c.989T&gt;C TP53 DNA sequence variants were not previously described in AML according Catalogue of Somatic Mutations In Cancer database. Median OS in t-AML with TP53 mutation vs without was 4 vs 7 months (P = .398) (Fig.1D). Conslusions: Our study brings detailed analysis of clinical outcome of t-AML. Patients with t-AML undergoing intensive treatment, younger than 65 years and with t-APL have significantly higher OS rates. On the contrary t-AML patients classified as adverse genetic ELN2017 subgroup have poorer OS rates. Treatment strategy in t-AML should rely on performing alloHCT possibly soon. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
pp. 110816
Author(s):  
Haoming Wu ◽  
Yang Wang ◽  
Xinyu Hao ◽  
Lu Meng ◽  
Huiying Li ◽  
...  

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