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Red blood cell transfusion independence (RBC-TI) is an important goal in treating lower-risk myelodysplastic syndromes with ring sideroblasts. In the phase 3 MEDALIST study, RBC-TI of ≥ 8 weeks was achieved by significantly more luspatercept- versus placebo-treated patients in the first 24 weeks of treatment. In this post hoc analysis, we evaluated RBC transfusion units and visits based on patients’ baseline transfusion burden level and the clinical benefit of luspatercept treatment beyond week 25 in initial luspatercept nonresponders (patients who did not achieve RBC-TI ≥ 8 weeks by week 25) but continued luspatercept up to 144 weeks. RBC transfusion burden, erythroid response, serum ferritin levels, and hemoglobin levels relative to baseline were evaluated. Through week 25, fewer RBC transfusion units and visits were observed in luspatercept-treated patients versus placebo, regardless of baseline transfusion burden. This continued through 144 weeks of luspatercept treatment, particularly in patients with low baseline transfusion burden. Sixty-eight patients were initial nonresponders at week 25 but continued treatment; most (81%) received the maximum dose of luspatercept (1.75 mg/kg). Sixteen percent achieved RBC-TI for ≥ 8 weeks during weeks 25–48, 26% had reduced RBC transfusion burden, 10% achieved an erythroid response, 44% had reduced serum ferritin, and hemoglobin levels increased an average of 1.3 g/dL from baseline. These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders. Trial registration: NCT02631070.

Amaç: Yıllardır erişkin literatürünün gölgesinde kalmış olan pediatrik akut pankreatit çalışmaları, pediatrik şiddet sınıflamasının kabul edilmesinden sonra ivme kazanmıştır. Artık hangi hastalarda ciddi hastalık gelişeceğini erken aşamada hızla öngörebilecek inflamatuar biyobelirteçlerin belirlenmesine ihtiyaç vardır. Bu çalışmanın amacı, sistemik immün-enflamasyon indeksi (SII) ve nötrofil-lenfosit oranı (NLO) gibi inflamatuar biyobelirteçlerin erken prediktör olarak etkinliğini değerlendirmek ve eşik değerler belirlemekti. Hastalar ve Yöntem: 2019-2022 yılları arasında akut pankreatit tanısı alan 53 çocuğun klinik özellikleri, laboratuvar test sonuçları ve görüntüleme bulguları retrospektif olarak değerlendirildi. Hastalar şiddetine göre “hafif” ve “orta şiddetli-şiddetli” olarak iki gruba ayrıldı. Gruplar inflamatuar belirteçler açısından karşılaştırıldı. Hastalık şiddetini öngören faktörler ROC eğrisi analizi ile incelendi. Anlamlı eşik değerler için duyarlılık, özgüllük, pozitif prediktif değer (PPD) ve negatif prediktif değer (NPD) hesaplandı. Bulgular: NLO ve SII değerleri “orta şiddetli-şiddetli” grupta “hafif” gruba göre istatistiksel olarak anlamlı derecede yüksekti (tümü için p

Among the difficulties of living with β-thalassemia, patients frequently require blood transfusions and experience iron overload. As serum ferritin (SF) provides an indication of potential iron overload, we conducted a systematic literature review (SLR) to assess whether SF levels are associated with clinical and economic burden and patient-reported outcomes (PROs). The SLR was conducted on 23 April 2020 and followed by analysis of the literature. Dual-screening was performed at the title, abstract, and full-text levels using predefined inclusion and exclusion criteria. Ten studies identified by the SLR were eligible for inclusion in the analysis. Seven studies were conducted in Europe, and most were prospective or retrospective in design. The patient populations had a median age of 20.7–42.6 years, with a percentage of men of 38–80%. Sparse data were found on the correlation between SF levels and mortality, and hepatic, skeletal, and cardiac complications; however, in general, higher SF levels were associated with worsened outcomes. The bulk of the evidence reported on the significant association between higher SF levels and endocrine dysfunction in its many presentations, including a 14-fold increase in the risk of diabetes for patients with persistently elevated SF levels. No studies reporting data on PROs or economic burden were identified by the SLR. SF levels provide another option for prognostic assessment to predict a range of clinical outcomes in patients with β-thalassemia.

Migraine is a leading cause of disability globally. Individuals with migraine experience reduced work productivity and greater health care costs compared with the general population. The Migraine Impact Model (MIM) is an interactive calculator developed to estimate the economic burden of migraine on United States-based employers. We demonstrate use of the model with 4 case studies from different industries (education, manufacturing, retail/trade, and entertainment). The MIM estimates migraine prevalence among employees and the employer's annual migraine-associated costs by applying published, licensed, and publicly available data and several underlying assumptions to employee population information that is inputted by users. User inputs include the employer's industry, geographic location, and workforce characteristics (number of employees, gender distribution, and average age and compensation). Model outputs include estimated migraine prevalence, annual workdays affected by migraine, and annual migraine-associated indirect and direct costs to the employer. In the case studies presented, workforce size ranged from 18,800 to 250,000, representing midsized to larger employers. Employee gender distribution ranged from 29% to 74% women, and mean employee age was either 41 or 44 years. The model-estimated percentage of employees with migraine ranged from 14% to 19%. The model projected approximately 60,000 to 686,000 annual workdays to be affected by lost productive time due to migraine (often referred to as "absenteeism" and "presenteeism") and estimated annual indirect costs to total between 6.2 and 8.5 times the annual direct costs. The MIM estimates the economic burden of migraine on a company's workforce, which may aid employers in making data-driven decisions to reduce that burden for employees and business.

Anemia is the most common form of cytopenia in patients with myelodysplastic syndromes (MDS), who require chronic red blood cell transfusions and may present high serum ferritin (SF) levels as a result of iron overload. To better understand the potential effects of high SF levels, we conducted a systematic literature review (SLR) to identify evidence on the relationship between SF levels and clinical, economic, or humanistic outcomes in adult patients with MDS. Of 267 references identified, 21 were included. No studies assessing SF levels and their relationship with humanistic or economic outcomes were identified. Increased SF levels were an indicator of worse overall survival and other worsened outcomes; however, the association was not consistently significant. SF levels were a significant prognostic factor for relapse incidence of MDS and showed a significant positive correlation with number of blood units transfused but were not associated with progression to acute myeloid leukemia or the time to transformation. Higher SF levels were also an indicator of a lower likelihood of leukemia-free survival, relapse-free survival, and event-free survival. The SLR suggests that SF levels are associated with clinical outcomes in MDS, with higher levels correlated with number of blood units transfused, frequently indicating worse outcomes.

Background In patients with non-transfusion-dependent beta-thalassaemia, haemoglobin concentrations lower than 10 g/dL are associated with a higher risk of morbidity, mortality, and impaired quality of life. No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent beta-thalassaemia, other than transfusion therapy administered infrequently in accordance with patients' needs. We assessed the efficacy and safety of luspatercept versus placebo in patients with non-transfusion-dependent beta-thalassaemia.Methods We did a phase 2, randomised, double-blind, multicentre, placebo-controlled trial in 12 centres in six countries (Thailand [n=1], Lebanon [n=1], Greece [n=2], Italy [n=5], the UK [n=1], and the USA [n=2]). Eligible patients were aged 18 years or older, had confirmed diagnosis of beta-thalassaemia or haemoglobin E/beta-thalassaemia (concomitant a-globin deletion, mutation, or duplication were allowed), and a baseline haemoglobin concentration of 10.0 g/dL or lower. All patients were non-transfusion-dependent. Patients were randomly assigned (2:1) to luspatercept or placebo using an interactive response technology system and stratified by baseline haemoglobin concentration (>= 8.5 g/dL vs = 3 vs

OBJECTIVES To compare the racial/ethnic differences in treatment quality among youth with primary care provider-initiated versus mental health specialist-initiated care for major depressive disorders (MDD). METHODS A retrospective cohort study was conducted using the 2005-2007 Medicaid claims data from Texas. Youth aged 10-20 during the study period were identified if they had two consecutive MDD diagnoses and received either medications for MDD or psychotherapy. Patients who received ≥84 days of medications and/or ≥4 sessions of psychotherapy for MDD treatment during 4 months of follow-up were considered meeting the minimum adequacy of treatment. RESULTS The generalized linear multilevel model (MLM) analysis revealed that both Hispanics and Blacks were approximately 30% less likely to receive adequate treatment (Hispanics - OR: 0.67; 95% CI: 0.6-0.8) (Blacks - OR: 0.66; 95% CI: 0.6-0.8) and Hispanic children were 50% more likely to undergo MH-related hospitalization (OR: 1.53; 95% CI: 1.1-2.2) compared to their White counterparts. The odds of meeting the minimum MDD treatment adequacy were comparable between pediatric MDD cases first identified by primary care providers (PCP-I) and psychiatrists (PSY-I) (PCP-I vs. PSY-I: OR: 0.97; 95% CI: 0.8-1.2), and slightly lower in those first identified by social workers/psychologists (SWP-I) as compared to PSY-I (SWP-I vs. PSY-I: OR: 0.81; 95% CI: 0.7-0.9). In all models, the interaction between race/ethnicity and type of provider who initiated MDD care was not statistically significant. CONCLUSIONS Minority youths received less adequate MDD treatment compared to Whites. Hispanic children had the highest risk of having mental health-related hospitalization. The specialty of provider who initiated MDD care had limited impact on treatment quality and was not associated with the racial/ethnic variations in treatment completion and mental health-related hospitalizations.

Background: Patients with multiple myeloma (MM) generally progress to being relapse/refractory (RR), having received several lines of treatment with various dosing frequencies and administration modalities, which impact patient satisfaction and experience. While there is still no cure, patients live longer but with potential burden attributable to treatment. A fit-for-purpose patient-reported outcome measure (PROM) assessing patient satisfaction and experience is missing for RRMM.Methods: We developed the Satisfaction and Experience Questionnaire (SEQ) for MM to measure patient satisfaction and experience, based on concepts identified from a literature review and nurse/patient perceptions about patient experiences. Online focus groups were conducted with oncology nurses who treat patients with MM to provide expert opinion, followed by concept elicitation and cognitive patient interviews. A preliminary SEQ-MM measure was first drafted based on desk research. Patient feedback from the cognitive interviews resulted in revisions to the preliminary SEQ-MM’s instructions, item wording, and response options between rounds. Content analysis was conducted to assess concept frequency mentioned during the concept elicitation focus group, and an item tracking table documented the SEQ-MM revisions based on cognitive interviews.Results: Three oncology nurses and 10 patients with RRMM participated in the focus groups. Oncology nurses reported treating 17 patients with MM per week, of which 33% were patients with RRMM. Study patients were primarily male (70%), with mean age of 56 (median range: 47 to 71). The most commonly reported satisfaction and experience concepts were related to: satisfaction with treatment (50%), experience with treatment (50%), relationship with healthcare practitioners (50%), time burden (50%), side effects (40%), and avoiding relapse (40%). The SEQ-MM was revised to include 15 items capturing: treatment burden (five items), time burden (five items), travel burden (two items), treatment compliance (one item), general satisfaction (one item), and an overall satisfaction item (one item).Conclusions: The SEQ-MM v1.0 evaluates the important facets of satisfaction and experience in patients with RRMM receiving treatment. This tool can be used to assess facets of treatment in MM that might complement health-related quality of life data Additional work is needed to examine item performance, scoring, and psychometric properties.

Background Several options for granulocyte colony-stimulating factor (G-CSF) prophylaxis of chemotherapy-induced febrile neutropenia are available to patients worldwide. We have developed a novel patient-reported outcome measure, the Satisfaction and Experience Questionnaire for G-CSF (SEQ-G-CSF), to help understand patients’ perspectives of and satisfaction with different G-CSF options. Results Three oncology nurses and 40 adult oncology patients in the United States were enrolled and participated in focus group discussions to develop and refine the SEQ-G-CSF. Nurses had ≥ 5 years of experience treating oncology patients and were currently involved in the management of oncology patients receiving G-CSF prophylaxis. The patients had breast cancer, lung cancer, non-Hodgkin lymphoma, or prostate cancer (10 patients in each group) and were receiving G-CSF prophylaxis via injection or the on-body injector (OBI) device. The preliminary SEQ-G-CSF contained an item relevance questionnaire and three SEQ modules (sociodemographic, medical history, and G-CSF–related healthcare characteristics questionnaires). Twenty-one patients (53% of total sample size) discussed their experience and satisfaction with G-CSF. Their most common experiences were G-CSF effectiveness, convenience and benefits of the OBI, and relationships with healthcare providers. Side effects and having to undergo additional treatment were also reported. Satisfaction with aspects of G-CSF included the OBI and effectiveness of G-CSF treatment; dissatisfaction included inconvenience (having to return to the clinic the next day and administration of the injection) and the insurance approval process. The SEQ-G-CSF was finalized after three rounds of cognitive interviews and includes five domains related to general satisfaction (one item), treatment burden (four items), travel burden (two items), time burden (four items), and treatment compliance (two items). Conclusions The SEQ-G-CSF is a novel instrument that quantifies a patient’s experience and satisfaction with different G-CSF options using 13 easy-to-understand items. This study provides evidence for the content validity of SEQ-G-CSF. Although further psychometric testing is required, the SEQ-G-CSF may be a useful addition to clinical trials, observational studies, and clinical practice.

Introduction: Beta-thalassemia is a hereditary blood disorder with some patients requiring frequent blood transfusions. Lifelong management of the disease and its complications imposes a severe burden on patients. This study aimed to understand the indirect costs and humanistic burden, treatment preferences, and perceptions of treatment and outcomes in patients with beta-thalassemia. Methods: Systematic literature searches were conducted in Embase, MEDLINE, and MEDLINE In-Process to identify articles on patients with beta-thalassemia published between November 2010 and 2020. Studies were included if they reported on patients with beta-thalassemia of any age regarding indirect costs, health-related quality of life (HRQoL), patient/caregiver preference, and qualitative outcomes in observational, economic, and preference elicitation studies. Search methods followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane. Results: Searches yielded 2387 records; 95 publications were included (Figure). The mean annual costs due to productivity losses in patients with transfusion-dependent beta-thalassemia (TDT) was 24% of all treatment costs. The cost of lost welfare due to pain and suffering in TDT in Iran in 2015 was USD 1360.50 per year per patient. Lost opportunities for TDT patients in Iran were highest in the age group 31-40 years and lowest in the age group 0-10 years. Lost opportunities for patients' families were highest in the age group 11-20 years. The mean annual transportation cost for TDT patients in Iran for visits to hospitals was EUR 132.77 (standard deviation [SD] 15.50). The indirect burden of absenteeism due to transfusion ranged from 13.5 to 30 days in patients and 19 days in caregivers, annually. Mean indirect burden due to disease management in TDT patients was 592 min (SD 349) on transfusion days (for activities including undergoing transfusion, cross-matching of blood, arranging childcare, arranging insurance payments) and 91 min (SD 221) on non-transfusion days. No studies on indirect costs were identified in the non-transfusion dependent beta-thalassemia (NTDT) population. Blood transfusion is used to reduce pain and fatigue in TDT patients and scores for fatigue and pain were worse for a period of 5 days before transfusion (mean Brief Fatigue Inventory score 5.05 vs 4.29; mean Brief Pain Inventory-Short Forms score 4.33 vs 3.85). HRQoL outcomes were reported to be associated with age (better HRQoL in ≤14 years of age, P=0.015, P=0.008), sex (better HRQoL in males, P=0.035, P=0.041, P=0.009), lower serum ferritin (better HRQoL, P=0.05, P=0.004), compliance to iron chelation therapies (better HRQoL, P50% of TDT patients suffered from mild to severe stress, anxiety, and depression. In TDT children, mental health was the most affected domain of SF-36 compared to healthy peers (48.6 vs 96.6, P Patient preference and qualitative studies were conducted in low- and middle-income countries and findings mostly corresponded to results from HRQoL studies. Patients/caregivers frequently reported feelings of uncertainty, anxiety, depression, and thoughts of dying. Social stigma substantially affected the lives of those affected by beta-thalassemia and contributed to adverse financial impacts. Conclusions: TDT is associated with high indirect costs, including productivity losses, absenteeism, transportation cost, and societal losses. Further research is needed to understand the indirect cost burden on NTDT patients. The findings highlight the unmet need for novel therapies, and optimal disease management approaches to decrease the economic burden of TDT in patients and their caregivers. Figure 1 Figure 1. Disclosures Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Resonance Health: Research Funding; CRISPR Therapeutics: Consultancy; SLN Therapeutics: Consultancy; Imara: Research Funding; Protagonist: Membership on an entity's Board of Directors or advisory committees, Research Funding; LaJolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ionis Pharmaceuticals: Research Funding. Purushotham: Evidera: Consultancy, Current Employment. Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Deshpande: Evidera Ltd: Consultancy, Current Employment. Potrata: Evidera Ltd: Current Employment. Trapali: Evidera Ltd: Consultancy, Current Employment. Dixit: Evidera: Current Employment. Shah: Bristol Myers Squibb: Honoraria.

7056 Background: Luspatercept was previously shown to improve anemia in the phase 3 MEDALIST trial of pts with LR-MDS ineligible, intolerant, or refractory to erythropoiesis-stimulating agents (ESAs). Here, we report the long-term clinical value of luspatercept treatment (Tx) in pts from the MEDALIST study including dosing and rates of progression to acute myeloid leukemia (AML) and high-risk MDS (HR-MDS). Methods: Eligible pts were ≥ 18 y of age, had LR-MDS requiring regular red blood cell (RBC) transfusions, and were ineligible/intolerant or refractory to ESAs. Pts were randomized 2:1 to subcutaneous luspatercept or placebo every 3 wk for 24 wk. The primary endpoint was RBC transfusion independence (RBC-TI) ≥ 8 wk during wk 1–24. MEDALIST pts were eligible for enrollment into the long-term follow-up study. Median duration of Tx and cumulative duration of response were determined by Kaplan–Meier (KM) analysis. Total person-years for pts at risk of HR-MDS/AML progression was calculated from LR-MDS diagnosis to HR-MDS/AML diagnosis, or to last HR-MDS/AML follow-up date for pts who did not progress. Results: As of January 15, 2021, the median duration of Tx was 11.70 (95% CI, 8.97–16.33) mo for luspatercept pts and 5.52 (95% CI, 5.52–5.59) mo for placebo pts. Of those enrolled in MEDALIST, 106/153 (69.3%) pts receiving luspatercept and 64/76 (84.2%) receiving placebo escalated to the maximum dose of 1.75 mg/kg. During the entire Tx phase, RBC-TI ≥ 8 wk was observed in 74/153 (48.4%) and 12/76 (15.8%) pts in the luspatercept and placebo arms, respectively, with a median cumulative duration of response of 80.7 (95% CI, 53.71–154.14) wk and 21.0 (95% CI, 10.86–NE) wk, respectively. During the entire Tx period, RBC-TI ≥ 16 wk was observed in 48/153 (31.4%) and 6/76 (7.9%) pts in the luspatercept and placebo arms, respectively (Table). Among pts randomized to luspatercept, 13/153 (8.5%) progressed to HR-MDS/AML during the entire Tx period, compared with 5/76 (6.6%) for placebo. The total person-years for pts randomized to luspatercept at risk of progressing to HR-MDS/AML was 401.7 y vs 190.9 y for placebo. Conclusions: Pts receiving luspatercept had an extended period of clinical benefit and > 50% of pts continued to receive luspatercept for > 1 y, the majority of whom underwent dose escalations to achieve an optimal response. Pts experienced durable responses with luspatercept, with a median cumulative duration of RBC-TI response of approximately 20 mo. Pts receiving luspatercept also appeared to have a longer time to HR-MDS/AML progression than those receiving placebo.[Table: see text]

Introduction: Patients with LR-MDS who are refractory or ineligible for treatment with erythropoiesis-stimulating agents (ESAs) have limited treatment options for anemia. Luspatercept is a first-in-class erythroid maturation agent that enhances late-stage erythropoiesis, and is approved by the US FDA for the treatment of anemia in adult patients with LR-MDS with ring sideroblasts (RS) or MDS/myeloproliferative neoplasm with RS and thrombocytosis after ESA failure. In the randomized, double-blind, phase 3 MEDALIST study, luspatercept significantly reduced transfusion burden versus placebo in patients with LR-MDS (NCT02631070; Fenaux P, et al. N Engl J Med 2020;382:140-151). Here we report additional analyses from the final data cut of the MEDALIST study, including: duration of treatment and red blood cell transfusion independence (RBC-TI) response; the number of responses per patient; exposure-adjusted rates of treatment-emergent adverse event (TEAE); and time to progression to AML. Methods: Eligible patients were ≥ 18 years of age; had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS; were refractory, intolerant, or unlikely to respond to ESAs (serum erythropoietin > 200 U/L); and required regular RBC transfusions. Patients were randomized 2:1 to luspatercept (starting dose 1.0 mg/kg, with titration up to 1.75 mg/kg) or placebo, administered subcutaneously every 3 weeks (wk). The primary endpoint was achievement of RBC-TI ≥ 8 wk during the first 24 wk of treatment. The duration of treatment in wk was calculated by (1 + the number of days between first dose and end of treatment) / 7. End of treatment date was either the last dose date plus 20 days, the study discontinuation date, or the death date, whichever was earlier. Duration of response was defined as the longest duration of RBC-TI response during the entire treatment period for patients who achieved RBC-TI ≥ 8 wk during wk 1-24 or wk 1-48. Exposure-adjusted incidence rates were calculated per 100 patient-years for TEAEs (any grade) in ≥ 5% of patients in any treatment group. Time to AML progression was defined as the time between the randomization date and the date of first AML diagnosis. Results: As of November 26, 2020, the median duration of treatment for patients randomized to luspatercept was 50.9 wk (range 6-207) versus 24.0 wk (range 7-103) for placebo. Patients randomized to luspatercept received a median of 17 doses (range 2-66) of treatment versus 8 doses (range 3-34) for placebo. Overall, 58 of 153 (37.9%) patients who received luspatercept achieved RBC-TI during any consecutive 8-wk period during wk 1-24, versus 10 of 76 (13.2%) for placebo. Of those achieving a response (RBC-TI ≥ 8 wk) during wk 1-24, the median duration of RBC-TI was 30.2 wk (range 8.1-201.1) for patients randomized to luspatercept versus 13.6 wk (range 9.1-66.4) for placebo, and 29.9 wk (range 8.1-201.1) for patients randomized to luspatercept versus 17.4 wk (range 9.1-66.4) for placebo, for those who responded during wk 1-48. Among patients who responded during wk 1-24 in the luspatercept arm, 17 (29.3%), 13 (22.4%), and 16 (27.6%) patients experienced 2, 3, or ≥ 4 separate RBC-TI ≥ 8-wk response events during the entire treatment period, versus 3 (30%) and 1 (10%) patients in the placebo arm, who experienced 2 or 3 response events. The only TEAEs with exposure-adjusted incidence rates ≥ 5 per 100 person-years higher in patients randomized to luspatercept versus placebo were: diarrhea (25.8 versus 18.4); dizziness (19.2 versus 8.9); nausea (20.1 versus 13.7); bronchitis (10.7 versus 2.2); vertigo (5.8 versus 0); and influenza (5.3 versus 0). Four of 153 (2.6%) patients randomized to luspatercept experienced progression to AML versus 3 of 76 (3.9%) patients randomized to placebo. The median time from randomization to AML progression for patients randomized to luspatercept was 61.7 months (range 56.7-223.6) versus 32.7 months (range 30.1-60.4) for placebo. Conclusions: Up through wk 48, patients randomized to luspatercept in the MEDALIST study remained on treatment longer and had more durable and repeated episodes of RBC-TI response events than placebo. Luspatercept had a tolerable safety profile when adjusted for exposure and patients receiving luspatercept had a longer time to AML progression than placebo. Luspatercept demonstrated durable responses over a longer time period in patients with anemia who have limited treatment options. Disclosures Platzbecker: Janssen: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Celgene/BMS: Honoraria; Geron: Honoraria; AbbVie: Honoraria. Santini: Astex: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Komrokji: Geron: Consultancy; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Speakers Bureau; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy; AbbVie: Consultancy. Zeidan: Daiichi Sankyo: Consultancy; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Astex: Research Funding; Astellas: Consultancy; Pfizer: Other: Travel support, Research Funding; Jazz: Consultancy; Epizyme: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; AstraZeneca: Consultancy; BioCryst: Other: Clinical Trial Committees; Janssen: Consultancy; Geron: Other: Clinical Trial Committees; Aprea: Consultancy, Research Funding; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Kura: Consultancy, Other: Clinical Trial Committees; BeyondSpring: Consultancy; Genentech: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Jasper: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Agios: Consultancy; ADC Therapeutics: Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Buckstein: Celgene: Research Funding; Otsuka: Research Funding; TAIHO: Research Funding; Takeda: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees. Rose: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Fabre: BMS: Current Employment. Miteva: BMS: Current Employment. Zhang: BMS: Current Employment, Current equity holder in publicly-traded company, Other: Patents & Royalties . Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Hughes: BMS: Current Employment. Fenaux: Novartis: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.

Introduction: Patients (pts) with non-transfusion-dependent β-thalassemia (NTDT) suffer from chronic anemia due to ineffective erythropoiesis. Low hemoglobin (Hb) levels in pts with anemia are associated with development of clinical complications and poor quality of life (QoL). There are no approved treatments for NTDT-associated anemia. Luspatercept has been shown to increase Hb levels in pts with NTDT in the BEYOND study (Taher AT, et al. HemaSphere 2021;5[Suppl 2];Abstract S101). This Hb increase was correlated with improvement in the NTDT Patient-Reported Outcomes (NTDT-PRO) Tiredness/Weakness (T/W) domain. Here we report the effect of luspatercept on red blood cell transfusion (RBCT) burden and QoL outcomes in pts with NTDT in the BEYOND study. Methods: Eligible pts with Hb ≤ 10 g/dL were randomized to luspatercept (1.0-1.25 mg/kg) or placebo (PBO) subcutaneously for ≥ 48 weeks (wk). The disease-specific instrument NTDT-PRO, measuring chronic anemia symptoms in pts with NTDT, was administered to pts as a daily diary starting on the 7 days prior to Dose 1, Day 1, until wk 24, and thereafter over the 7 days prior to dosing at every other dosing visit. The 36-item Short Form Health Survey Version 2 (SF-36 v2) and Functional Assessment of Chronic Illness Therapy-Fatigue, Fatigue subscale (FACIT-F FS) were completed by the pts at screening and at every other dosing visit thereafter starting with day 1, dose 1. Mean change from baseline in NTDT-PRO T/W and Shortness of Breath (SoB) domain scores and in FACIT-F FS score over a continuous 12-wk interval during wk 13 to 24 and wk 37 to 48 was assessed using analysis of covariance (ANCOVA) with treatment group and other relevant covariates in the model. The SF-36 v2 physical component summary (PCS) and mental component summary (MCS) mean change from baseline at wk 24 and wk 48 were analyzed using a mixed-effect repeated measures model with intercept and time as the random effect. The model included change from baseline scores up to wk 48 as the outcome, treatment group assignment, time, baseline scores, randomization stratification factor(s), time-by-baseline score, and time-by-treatment group assignment terms. Descriptive statistics were used to ascertain the number of RBC units, RBCT events, reason for RBCT, and time to first RBCT event. Results: Of 145 pts, 96 were randomized to luspatercept and 49 to PBO. NTDT-PRO analyses were conducted in the intention-to-treat population. The QoL-evaluable populations for FACIT-F FS and SF-36 v2 analyses (luspatercept vs PBO) were: 94 vs 47 and 92 vs 46 pts, respectively. Baseline domain scores of the QoL measures were comparable between the 2 treatment arms. Mean change from baseline (least squares mean [LSM]) in NTDT-PRO T/W domain score (wk 13-24) was −0.68 vs −0.20 for luspatercept vs PBO, respectively (LSM difference [LSMD] −0.48; 95% confidence interval [CI] −1.03 to 0.08; P = 0.0924). Improvement was more pronounced in the luspatercept arm during wk 37-48 (Table). Within the NTDT-PRO SoB domain, mean change from baseline (wk 13-24) was −0.46 vs 0.02 for luspatercept vs PBO, respectively (LSMD −0.49; 95% CI −1.02 to 0.04; P = 0.0721) and during wk 37-48 was −0.59 vs 0.47 for luspatercept vs PBO, respectively (LSMD −1.07; 95% CI −1.80 to −0.33; P = 0.0047) (Table). Favorable QoL improvements were also observed in the luspatercept arm vs PBO and increased over time for both FACIT-F FS and SF-36 v2 assessments (Table). During wk 1-48, 79/96 (82.3%) luspatercept vs 22/49 (44.9%) PBO pts were RBCT-free (P < 0.0001); 5/13 (38.5%) and 1/7 (14.3%) pts treated with luspatercept and PBO, respectively, who received RBCTs at baseline, became RBCT-free during wk 1-48. Among all pts who received RBCTs during wk 1-48, pts receiving luspatercept required fewer RBCTs compared with pts receiving PBO (median 1.0 RBCTs [range 1.0-6.0] vs 2.0 [1.0-7.0], respectively), and fewer RBC units (median 2.0 units [range 1.0-8.0] vs 2.5 [1.0-13.0], respectively). Time to first RBCT (median [range] days) was longer for pts receiving luspatercept vs PBO (336 [2.0-336.0] vs 260.0 [9.0-336.0], respectively) and, in both arms, the main reasons for receiving RBCTs were anemia and surgery. Conclusions: In pts with NTDT, luspatercept improved RBCT burden and QoL compared with PBO. The improvement was more pronounced over time and consistent across 3 QoL-measuring instruments. Most pts receiving luspatercept remained RBCT-free during wk 1-48 of treatment. Figure 1 Figure 1. Disclosures Kattamis: Novartis: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Consultancy, Honoraria; VIFOR: Consultancy; IONIS: Consultancy; Agios Pharmaceuticals: Consultancy; Amgen: Consultancy. Viprakasit: Ionis Pharmaceuticals,: Consultancy, Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; La Jolla Pharmaceuticals: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Vifor Pharma: Consultancy, Research Funding. Cappellini: IONIS Pharmaceuticals: Consultancy; Protagonist Therapeutics: Research Funding; La Jolla: Research Funding; Vifor: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CRISPR Therapeutics: Research Funding. Voskaridou: NOVARTIS: Research Funding; IMARA: Research Funding; BMS: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; PROTAGONIST: Research Funding; ADDMEDICA: Consultancy, Research Funding. Piga: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acceleron: Research Funding. Porter: Celgene (BMS): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vifor: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria; Protagonism: Honoraria; La Jolla Pharmaceuticals: Honoraria. Coates: UpToDate: Patents & Royalties; Sangamo: Consultancy; Forma Pharma: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Apo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chiesi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vifor Pharma: Consultancy. Forni: Bluebirdbio: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Shetty: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Miteva: BMS: Current Employment. Esposito: Bristol Myers Squibb: Current Employment. Kuo: Bristol Myers Squibb: Current Employment. Guo: Gilead: Consultancy; Janssen: Consultancy; UCB: Consultancy; Daiichi Sankyo: Consultancy; EMD Serono: Consultancy; Bristol Myers Squibb: Consultancy; Evidera: Current Employment. Pelligra: Evidera: Current Employment; Bristol Myers Squibb: Research Funding. Lord-Bessen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Yucel: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Taher: Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Vifor Pharma: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy, Research Funding.

Febrile neutropenia (FN) is a life-threatening complication of chemotherapy that can lead to hospitalizations, chemotherapy dose reductions or delays, and mortality. Granulocyte colony-stimulating factor (G-CSF) prophylaxis reduces the incidence of FN, enabling patients to undergo and remain on myelosuppressive chemotherapy. We estimate the benefits of continuing current G-CSF use patterns and an alternative that aligns prophylactic G-CSF use with guideline recommendations.Using The Health Economics Medical Innovation Simulation microsimulation, we estimated lifetime social value (SV) of prophylactic G-CSF for a nationally representative US population with breast, lung, and gynecological cancers and non-Hodgkin lymphoma.SV estimates included the cost of G-CSF, FN, chemotherapy relative dose intensity (RDI) less than 85% (RDI85%), medical spending, and deaths for 3 scenarios: current use (current G-CSF use), targeted use (100% G-CSF use among patients with high FN risk), and reduced use (current G-CSF use reduced by 20% across all FN risk categories).Over 10 years, current use, compared with no G-CSF use, would decrease cases of FN by 3.3 million, prevent 354,000 cases of RDI85%, and generate $96 billion in SV. Compared with current use, targeted use would decrease cases of FN by an additional 3.3 million, prevent 355,000 more cases of RDI85%, and generate another $119 billion in SV. Reduced use would increase FN and RDI85%, lowering SV by $18 billion compared with current use.Current use of G-CSF prophylaxis would provide $96 billion in SV over the next 10 years. Targeting G-CSF prophylaxis to align with guidelines would more than double SV, highlighting the substantial value of appropriate FN risk assessment and targeted G-CSF prophylaxis.

Background and Objective: Malnutrition is a major complication of inflammatory bowel disease (IBD). Our aim of the study was to examine the effects of Modulen IBD supplementation, which was administered to IBD patients without limiting their daily diet in addition to medical treatment, on the clinical, laboratory, anthropometric values, and disease activities of these patients. Materials and Methods: Seventy three children with IBD were evaluated retrospectively. The cases were classified as those who had Crohn disease receiving (CD-M, n = 16) or not receiving Modulen IBD (CD, n = 19) and those who had ulcerative colitis receiving (UC-M, n = 13) or not receiving Modulen IBD (UC, n = 25). Disease activities, laboratory values, remission rates, and anthropometric measurements of the groups were compared. In addition to IBD treatment, Modulen IBD in which half of the daily calorie requirement was provided was given for eight weeks. Results: In the third month of treatment, 14 (88%) patients were in remission in CD-M group and eight (42%) patients were in remission in CD group. The height and weight z scores, which were low at the time of diagnosis, improved in the first week in CD-M group. Inflammatory parameters (UC) were significantly lower in the UC-M group compared to the UC group in first and third months. In the third month, eight (62%) patients in the UC-M group and four (16%) in the UC group were remitted clinically and in terms of laboratory values. Conclusions: TGF-&beta, rich enteral nutrition support in children with IBD is an easy, effective, and reliable approach. It was shown that TGF-&beta, rich enteral nutritional supplementation enabled the disease to enter the remission earlier, and contributed to the early recovery of weight and height scores.

Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their biosimilars are used to treat anaemia in MDS and, currently, epoetin alfa and darbepoetin alfa are commonly used and recommended by clinical guidelines. To better understand the evidence available on the use of ESAs for anaemia in lower-risk MDS, we conducted a systematic literature review to identify randomized and nonrandomized prospective studies reporting on clinical efficacy/effectiveness, patient-reported quality of life (QoL), and safety. We extended our review to include retrospective studies for darbepoetin alfa specifically and to ascertain the feasibility of completing an indirect network meta-analysis comparing epoetin and darbepoetin alfa. Overall, 53 articles reporting on 35 studies were included. The studies indicated a clinical benefit of ESAs, with benefits observed across key clinical outcomes. ESAs showed consistent improvement in erythroid response rates (ESA-naive, 45-73%; previous ESA exposure, 25-75%) and duration of response. Comparative studies demonstrated similar progression to acute myeloid leukaemia and several showed improved overall survival and QoL. Limited safety concerns were identified. This analysis confirmed ESA therapy should be the foremost first-line treatment of anaemia in most patients with lower-risk MDS who lack the 5q deletion.

Background Mistaken ingestion of all manner of toxic matter is common in childhood, but poisoning with fireworks and matchsticks is rare. Fireworks usually contain 10% yellow phosphorus and 50% potassium chlorate. Potassium chlorate is an extremely reactive and toxic agent that is used in fireworks and matchstick heads. Methods Eleven cases (7 females and 5 males; median age, 36 months [ranging from 24 to 48 months]) of poisoning after ingestion of fireworks and matchstick(s), between February 2008 and June 2014, were reviewed. Results The most common initial symptom was vomiting except for 2 cases in this group. Biochemical tests indicated that hyperphosphatemia was present in all patients, 8 patients (72.7%) had subclinical hepatic injury, 1 (9%) had acute hepatic failure, and 2 patients had no clinical or biochemical evidence of hepatic damage. Three patients had renal impairment, but none of them required dialysis. All of the patients recovered with supportive therapy except for 2 cases. One patient underwent cadaveric liver transplantation, whereas the other died because of circulatory dysfunction and respiratory failure due to pulmonary alveolar hemorrhage. Conclusions Without prompt intervention, poisoning with fireworks carries high morbidity and mortality in children. It can cause pulmonary hemorrhage, in addition to other organ damage, including liver and kidney. Hyperphosphatemia is common, as it was seen in all of the study patients.

Objective Emergency room (ER) visits are perceived with high costs and unpredictable outcomes. Although the association between Attention Deficit Hyperactivity Disorder (ADHD), stimulants and ER visits has been studied, the difference between the types of stimulants in terms of risk of ER visits has not been studied. Our objective is to identify the difference between the effects of long-acting and short-acting stimulant use in ADHD on ER visits in 18- to 35-year-old adults (n = 636) in the year 2011. Methods This retrospective secondary data analysis used the Medical Expenditure Panel Survey data for the year 2011. Univariate and multivariate logistic regression were used to evaluate risk factors, influencing the type of stimulant use on ER visits. Risk factor and stimulant interactions were also included. Key findings The risk of ER visits in long-acting stimulant users, among the uninsured, on adjusting for race, marital and insurance status, is 14.25 times (P = 0.001) the risk of ER visits in short-acting stimulant users. If they are insured, the risk of ER visits in long-acting stimulant users is 1.83 times the risk of ER visits in short-acting stimulant users (P = 0.26). Conclusions Long-acting stimulants increase the risk of ER visits for people who do not have insurance. Therefore, besides the type of stimulants, lack of insurance is also a risk factor for increased ER visits for young ADHD adult population in the USA.

Oculoauriculovertebral spectrum (OAVS) is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. Oculo-auriculovertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome presents frequently as the most severe form. Hemifacial microsomia appears to be an intermediate form. Here we report four cases with different phenotypic expressions. Case 1 had unilateral anotia with cardiac and urogenital abnormalities. Case 2 was an offspring of a diabetic mother, presenting with unilateral microtia, facial paralysis and sacral agenesis. Case 3 had unilateral anotia plus hemifacial microsomia and facial clefting accompanied to Hirsprung disease. Case 4 was presenting with microtia/preauricular tags plus hemifacial microsomia without accompanying any other system abnormalities. Two had a positive family history, one of them was represented an autosomal dominant (case 1), and the other was autosomal ressesive mode of inheritance (case 4). Based on these cases, we highlighted the heterogeneity of the presentation and genetic etiology of OAVS.

Introduction: Biloma is encapsulated collection of bile due to iatrogenic injury or abdominal trauma. The perforation of the extra-intrahepatic bile duct without any traumatic or iatrogenic injury is defined as spontaneous biloma. The spontaneous biloma is very rare and infrequently reachesto huge sizes. Previously described causes of spontaneous biloma include choledocholithiasis, acute cholecystitis, cholangiocarcinoma, pancreatic malignancy and hepatic abscesses or infarctions. Case Presentation: We describe the case of a huge spontaneous biloma in a 16-year-old girl patient with sclerosing cholangitis. She applied to our hospital for generalised abdominal distention and pain. There was no cholestasis at her admission, but, interestingly cholestasis developed on the tenth day of hospitalization.She was treated with percutaneous drainage, endoscopic sphincterotomy and stent placement into the common bile duct. After discharge, there was no recurrence at the three-month follow-up. Conclusions: To our knowledge, this is the first report in the literature of spontaneous biloma associated with sclerosing cholangitis.

e18859Background: Pegfilgrastim prophylaxis reduces risk of febrile neutropenia (FN) and administration is recommended at least 24 h after cytotoxic chemotherapy. The pegfilgrastim (Neulasta) OBI e...

Many systematic reviews resulted in claims on drug-drug interactions (DDIs) with proton pump inhibitors (PPIs). Such a large number begs for consensus on the clinical significance of findings.We critically evaluated the safety of PPI use with respect to DDIs with a meta-review of systematic reviews published between 1978 and 2015. We assessed the evidence by their reliability, repeatability, transparency, and objectivity according to the Assessment of Multiple Systematic Reviews (AMSTAR) criteria.Clinicians must assess risks for each PPI for certain comorbid conditions. DDIs don't substantiate class effect for PPIs; each PPI could induce unique DDIs. Concomitant use of PPIs with thienopyridines (e.g. clopidogrel) could be justified in patients without strong affinity to cytochrome CYP2C19 and with high risk of bleeding (e.g. patients with prior upper gastrointestinal bleeding, Helicobacter pylori infection, advanced age, steroid treatment, and nonsteroidal anti-inflammatory drug use). DDIs could occur in an AIDS subpopulation treated with highly active antiretroviral therapy (HAART). DDIs exist for cancer patients undergoing targeted therapy. Hypomagnesemia could increase in the setting of advanced age and polypharmacy. Omeprazole poses high risks owing to its pharmacokinetic DDI profile. Future systematic reviews should incorporate these additional risks for better clinical guidance.

We aimed to determine hemodynamic alterations in renal arteries that may have resulted from oral intake of sildenafil citrate in healthy volunteers.Twelve healthy volunteers were included in our study. Renal Doppler ultrasonography (US) was performed before the drug intake to assess the basal values. Maximum peak systolic velocity, and resistivity and pulsatility indices were measured from the segmental branches of both renal arteries in all the examinations. After the basal measurements 50 mg of sildenafil or placebo were randomly given to the 12 subjects. Renal Doppler US examinations were carried out 1 h after sildenafil or placebo intake. On the following day sildenafil was administered to the subjects who had previously taken placebo or vice versa. Renal Doppler US was repeated after 1 h. The effect of sildenafil on renal vascular hemodynamics was evaluated by comparison of basal values with postplacebo and postsildenafil values.No statistically significant differences were found between the basal values of bilateral renal arteries and maximum peak systolic velocity, and resistivity and pulsatility index values measured after the placebo or sildenafil intake.We demonstrated that single-dose sildenafil did not cause any significant effect on renal artery hemodynamics in healthy individuals.