bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of iron deficiency
Authors: Ning Shuoyan , Zeller Michelle P. 
Published: December 2019

AbstractIron deficiency (ID) affects billions of people worldwide and remains the leading cause of anemia with significant negative impacts on health. Our approach to ID and iron deficiency anemia (IDA) involves three steps (I3): (1) identification of ID/IDA, (2) investigation of and management of the underlying etiology of ID, and (3) iron repletion. Iron repletion options include oral and intravenous (IV) iron formulations. Oral iron remains a therapeutic option for the treatment of ID in stable patients, but there are many populations for whom IV iron is more effective. Therefore, IV iron should be considered when there are no contraindications, when poor response to oral iron is anticipated, when rapid hematologic responses are desired, and/or when there is availability of and accessibility to the product. Judicious use of red cell blood transfusion is recommended and should be considered only for severe, symptomatic IDA with hemodynamic instability. Identification and management of ID and IDA is a central pillar in patient blood management.
Management of liver complications in sickle cell disease
Authors: Suddle Abid R. 
Published: December 2019

Abstract
Liver disease is an important cause of morbidity and mortality in patients with sickle cell disease (SCD). Despite this, the natural history of liver disease is not well characterized and the evidence basis for specific therapeutic intervention is not robust. The spectrum of clinical liver disease encountered includes asymptomatic abnormalities of liver function; acute deteriorations in liver function, sometimes with a dramatic clinical phenotype; and decompensated chronic liver disease. In this paper, the pathophysiology and clinical presentation of patients with acute and chronic liver disease will be outlined. Advice will be given regarding initial assessment and investigation. The evidence for specific medical and surgical interventions will be reviewed, and management recommendations made for each specific clinical presentation. The potential role for liver transplantation will be considered in detail.
In MDS, is higher risk higher reward?
Authors: Sanz Guillermo F. 
Published: December 2019

Abstract
Patients with higher-risk myelodysplastic syndrome (HR-MDS) are defined by the original or revised International Prognostic Scoring System and specific genetic features. Treatment of HR-MDS is challenging. Allogeneic hematopoietic stem cell transplantation, the only curative approach, is feasible in a minority of fit or intermediate fitness patients aged &lt;70 to 75 years who are willing to face the risks of the procedure. Response to azacitidine and decitabine, the only approved drugs for HR-MDS and considered the standard of care, is partial and transient in most patients. The development of novel more personalized and efficient drugs is an unmet medical need. During the last decade, there have been substantial advances in understanding the multiple molecular, cellular, and immunological disturbances involved in the pathogenesis of myelodysplastic syndrome. As a result, a number of clinical and translational studies of new more focused treatment approaches for HR-MDS patients are underway. In contrast to acute myeloid leukemia, they have not resulted in any new drug approval. This review addresses the benefits and limitations of current treatment alternatives, offers a practical individualized treatment approach, and summarizes the clinical trials in progress for HR-MDS.
Selection of matched unrelated donors moving forward: from HLA allele counting to functional matching
Authors: Fleischhauer Katharina 
Published: December 2019

Abstract
Matched unrelated donors (URD) are the most frequent source of stem cells for allogeneic hematopoietic cell transplantation (HCT) to date, with HCT performed mainly under conventional immunosuppression by methotrexate and cyclosporine. In this setting, every single allelic donor–recipient mismatch for HLA-A, -B, -C, -DRB1 (8/8), but not for HLA-DQB1, -DPB1, has a significant negative effect on overall survival (OS). When several 8/8 HLA-matched URD are available, donor age is the most important factor impacting OS. Moving forward from the traditional way of counting the number of donor–recipient HLA allele mismatches to biology-driven algorithms for functional matching has led to the unraveling of an association between permissive, low-risk HLA-DPB1 mismatches and improved outcome after URD HCT for malignant disease but not for nonmalignant disease. Functional HLA matching might prove to have increasing importance for URD selection in the era of new immunosuppressive regimens that have the potential to substantially reshuffle the role of HLA mismatches in URD HCT.
Relapsed disease and aspects of undetectable MRD and treatment discontinuation
Authors: Eichhorst Barbara , Fürstenau Moritz , Hallek Michael 
Published: December 2019

AbstractContinuous treatment vs fixed duration of monotherapies and combinations of targeted agents are treatment options in relapsed chronic lymphocytic leukemia. The optimal choice of relapse treatment is dependent on the prior frontline therapy, duration of remission after frontline, genetic markers, and patients’ condition, including age and comorbidities. Combination therapies may result in deep responses with undetectable minimal residual disease (uMRD). Although uMRD is an excellent predictive marker for disease progression, it is rarely used in clinical practice and needs additional evaluation in clinical trials before discontinuation of therapy should be guided according to uMRD.
Evidence-Based Minireview: The role of IV iron in management of patients with iron-deficiency anemia presenting to the emergency department
Authors: Ramos Julia G. , Zeller Michelle P. 
Published: December 2019

Abstract
A 45-year-old woman with a history of uterine fibroids and abnormal uterine bleeding presents to the emergency department (ED) with presyncope and weakness. A gynecology consultation for definitive management was requested. The complete blood count demonstrates a hemoglobin (Hb) of 6.5 g/dL and a mean corpuscular volume (MCV) of 65 fL. What is the role of IV iron in managing iron-deficiency anemia (IDA) presenting to the ED/urgent care?
What to do with minimal residual disease testing in myeloma
Authors: Manasanch Elisabet E. 
Published: December 2019

Abstract
The role and use of minimal residual disease (MRD) testing has changed significantly over the past few years as it has become part of the routine care for response assessment in multiple myeloma. The most widely used standardized methods to assess MRD in myeloma in the bone marrow are multicolor flow cytometry and next-generation sequencing. Importantly, the depth of MRD negativity in the bone marrow correlates with improved progression-free survival and overall survival in myeloma. Whole-body position emission tomography–computed tomography and magnetic resonance imaging are also used to evaluate patchy and extramedullary disease, which may not be readily visible through bone marrow assessment. This article reviews a clinical case in which MRD testing, both in bone marrow and in functional imaging, is part of the standard of care. It also reviews the different modalities of MRD testing and current practice guidelines. Finally, patients with myeloma may be tested for MRD after treatment because this is part of the routine response assessment according to International Myeloma Working Group criteria and correlates with clinical outcomes. Important questions such as when to stop therapy for sustained MRD-negative patients or whether to change treatments for patients who go from MRD negative to positive without other evidence of disease relapse are being evaluated in clinical trials and remain controversial.
Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy
Authors: Al-Samkari Hanny , Connors Jean M. 
Published: December 2019

AbstractThe association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.
Treatment-naive CLL: lessons from phase 2 and phase 3 clinical trials
Authors: Woyach Jennifer A. 
Published: December 2019

Abstract
The management of chronic lymphocytic leukemia (CLL) has undergone dramatic changes over the previous 2 decades with the introduction of multiple new therapies and new combinations. Management of the newly diagnosed asymptomatic patient has not significantly changed outside of the development of a number of prognostic factors and the CLL International Prognostic Index, which is helpful in discussions regarding prognosis and likelihood of requiring treatment. When therapy is required, initial treatment of most patients now includes either the Bruton tyrosine kinase inhibitor ibrutinib or the B-cell lymphoma 2 inhibitor venetoclax in combination with obinutuzumab. Current frontline trials are focused on the optimal sequencing or combination of targeted therapies. In this review, we will discuss the management of previously untreated CLL with an emphasis on the clinical trials that have formed the standard of care, as well as those newer studies that are likely to form the next generation of therapy.
A sensitive chemiluminescence based immunoassay for the detection of cortisol and cortisone as stress biomarkers
Authors: Abdulsattar Jwan O. , Greenway Gillian M. 
Published: December 2019

AbstractAn electrochemically based antibody immobilization was used to perform environmentally and clinically relevant immunoassays for stress hormones biomarkers (cortisol and cortisone) using chemiluminescence (CL) detection. To achieve CL detection, the ferrocene tag on the antibodies was first oxidised, and this then acted as a catalyst for the luminol and hydrogen peroxide CL reaction. The conditions were optimised and measurements were made with an incubation time of 30 min. Using this approach limits of detection were obtained of 0.47 pg ml−1and 0.34 pg ml−1alsoR20.9912 and 0.9902 for cortisol and cortisone respectively with a linear concentration from 0 to 50 ng ml−1. The method was then applied to Zebrafish whole body and artificial saliva samples. For the Zebrafish sample recoveries of 91.0% and 90.0% were obtained with samples spiked with cortisol and cortisone, for artificial saliva the recoveries were 92.59% and 90.73% respectively. Interference studies showed only minor effects on the measurement of the analyte. A comparison between this procedure and the standard enzyme-linked immunosorbent assay (ELISA) procedure gave approximately the sameR2values.
Effects of psychological treatment of mental health problems in pregnant women to protect their offspring: randomised controlled trial
Authors: Burger Huibert , Verbeek Tjitte , Aris-Meijer Judith L. , Beijers Chantal , Mol Ben W. , Hollon Steven D. , Ormel Johan , van Pampus Mariëlle G. , Bockting Claudi L.H. 
Published: December 2019

BackgroundPerinatal depression and anxiety are associated with unfavourable child outcomes.AimsTo assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive–behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242.MethodPregnant women (n= 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT (n= 140) or CAU (n= 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother–infant bonding and child cognitive and motor development at age 18 months.ResultsIn total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI −1.82 to 4.57);t= 0.85,P= 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. Apost hocanalysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group.ConclusionsPrenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.
Randomized, Double-Blind, Pharmacokinetic Equivalence Trial Comparing DRL-Rituximab With MabThera in Patients With Diffuse Large B-Cell Lymphoma
Authors: Viswabandya Auro , Shah Sandip , Mukhopadhyay Asis , Nagarkar Rajnish Vasant , Batra Sonica Sachdeva , Lopez-Lazaro Luis , Kankanwadi Suresh , Srivastava Alok 
Published: December 2019

PURPOSE We sought to compare the pharmacokinetics (PKs) of DRL-rituximab (DRL_RI; potential biosimilar) and innovator rituximab MabThera (Roche, Grenzach-Wyhlen, Germany; reference medicinal product [RMP]) in patients with diffuse large B-cell lymphoma (DLBCL). Efficacy, pharmacodynamics (PDs), safety, and immunogenicity were also compared. PATIENTS AND METHODS We conducted a double-blind, parallel-group study in patients with untreated DLBCL who were eligible to receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Patients were randomly assigned at a one-to-one ratio to receive DRL_RI or RMP for six 21-day cycles of rituximab plus CHOP, with 18 months of follow-up after day 1, cycle 6 (C6). Primary end point was C1 PKs, measured as area under the plasma concentration–time curve from day 0 to 21 (AUC0-21 days) and maximum plasma concentration (Cmax). Equivalence was defined as 90% CIs for the DRL_RI/RMP geometric mean ratios (GMRs) within 80% and 125%. Secondary end points included efficacy noninferiority measured by objective response rate (ORR) at C6 and event-free survival and overall survival at 87 weeks, PK equivalence at C6 and PD equivalence (rate of B-cell depletion and repletion), safety, and immunogenicity. The trial was stopped after sufficient patients for primary end point evaluation were enrolled. Secondary end points are reported as observed. RESULTS A total of 151 patients were randomly assigned (DRL_RI, n = 76; RMP, n = 75). DRL_RI/RMP GMRs for AUC0-21 days and Cmax in C1 were 99.77 (90% CI, 87.60 to 113.63) and 96.19 (90% CI, 88.65 to 104.38), respectively. ORR at C6 for DRL_RI and RMP were 82.0% and 84.8%, respectively. Rates of B-cell depletion/repletion, immunogenicity, and adverse events were comparable in both groups. CONCLUSION DRL_RI and RMP had equivalent PKs, with comparable efficacy, PDs, safety, and immunogenicity.
Criminal Justice or Public Health: A Comparison of the Representation of the Crack Cocaine and Opioid Epidemics in the Media
Authors: Shachar Carmel , Wise Tess , Katznelson Gali , Campbell Andrea Louise 
Published: December 2019

AbstractContext: The opioid epidemic is a major US public health crisis. Its scope prompted significant public outreach, but this response triggered a series of journalistic articles comparing the opioid epidemic to the crack cocaine epidemic. Some authors claimed that the political response to the crack cocaine epidemic was criminal justice rather than medical in nature, motivated by divergent racial demographics.Methods: We examine these assertions by analyzing the language used in relevant newspaper articles. Using a national sample, we compare word frequencies from articles about crack cocaine in 1988–89 and opioids in 2016–17 to evaluate media framings. We also examine articles about methamphetamines in 1992–93 and heroin throughout the three eras to distinguish between narratives used to describe the crack cocaine and opioid epidemics.Findings: We find support for critics' hypotheses about the differential framing of the two epidemics: articles on the opioid epidemic are likelier to use medical terminology than criminal justice terminology while the reverse is true for crack cocaine articles.Conclusions: Our analysis suggests that race and legality may influence policy responses to substance-use epidemics. Comparisons also suggest that the evolution of the media narrative on substance use cannot alone account for the divergence in framing between the two epidemics.
Heavy and Explosive Training Differentially Affect Modeled Cyclic Muscle Power
Authors: TANGHE KIRA K. , MARTIN JAMES C. 
Published: December 2019

ABSTRACT

Introduction/Purpose
Muscular power is important in applications ranging from elite sport to activities of daily living. Results for improvements in power after resistance training have been mixed, possibly because of changes in muscle activation and deactivation rates. Our purpose was to determine the effects of heavy and explosive training programs on maximal power across a range of frequencies during cyclical contractions using a mathematical model.

Methods
Maximal force production and time constants for muscle activation and deactivation after heavy and explosive training programs were determined using previously reported data. A muscle–tendon model was subjected to sinusoidal length change, and activation and deactivation were set to maximize power for a range of cycle frequencies (0.5–3.0 Hz). Power for shortening/lengthening cycles was modeled for each training program and for a hypothetical periodized program with the best results from each program.

Results
The heavy training program increased strength by 26.8%, and increased time required for activation (20%) and deactivation (48%). The explosive training program increased strength by 10.8%, but decreased time required for activation (24%) and deactivation (10%). Increases in maximal power were similar after heavy (13.6%) and explosive (13.8%) training, but with different power–frequency relationships (optimal frequencies of 1.56 and 1.94 Hz for heavy and explosive, respectively). The hypothetical periodized program increased power by 30.3% (optimal frequency at 1.94 Hz).

Conclusion
Power during low-frequency movements (e.g., swimming) improved more after heavy training, whereas power during high-frequency movements (e.g., running) improved more after explosive training. These findings suggest that changes in time required for activation and deactivation in response to training are highly influential for maximal power across a range of functional frequencies, ultimately altering the ideal training regimen for specific activities.
Greater Lower Limb Fatigability in People with Prediabetes than Controls
Authors: SENEFELD JONATHON W. , HARMER ALISON R. , HUNTER SANDRA K. 
Published: December 2019

ABSTRACT

Introduction
The study purpose was to compare perceived fatigability and performance fatigability after high-velocity contractions with knee extensor muscles between people with prediabetes, people with type 2 diabetes (T2D), and controls without diabetes matched for age, body mass index, and physical activity.

Methods
Twenty people with prediabetes (11 men, 9 women: 63.1 ± 6.0 yr, 26.9 ± 4.2 kg·m−2, 8030 ± 3110 steps per day), 39 with T2D (23 men, 16 women: 61.2 ± 8.5 yr, 29.4 ± 6.4 kg·m−2, 8440 ± 4220 steps per day), and 27 controls (13 men, 14 women: 58.1 ± 9.4 yr, 27.3 ± 4.3 kg·m−2, 8400 ± 3000 steps per day) completed the Fatigue Impact Scale as a measure of perceived fatigability and a fatigue protocol including 120 maximal-effort, high-velocity concentric contractions (MVCC; 1 contraction/3 s) with the knee extensors using a submaximal load (30% maximum) to quantify performance fatigability. Electrical stimulation was used to assess voluntary activation and contractile function of the knee extensor muscles before and after the fatigue protocol.

Results
Fatigue Impact Scale scores were not different between people with prediabetes, people with T2D, and controls (12.5 ± 15.1, 18.3 ± 22.7, and 12.6 ± 18.6, respectively; P = 0.517). However, people with prediabetes had greater reductions in MVCC power during the fatigue protocol than did controls (31.8% ± 22.6% vs 22.1% ± 21.1%, P < 0.001), and both groups had lesser reductions than the T2D group (44.8% ± 21.9%, P < 0.001). Similarly, the prediabetes group had larger reductions in electrically evoked twitch amplitude than the control group (32.5% ± 24.9% vs 21.3% ± 33.0%, P < 0.001), but lesser reductions than those with T2D (44.0% ± 23.4%, P < 0.001). For all three groups, a greater decline in MVCC power was associated with larger reductions of twitch amplitude (r
2 = 0.350, P < 0.001).

Conclusion
People with prediabetes have greater performance fatigability of the knee extensors due to contractile mechanisms compared with controls, although less performance fatigability than that of people with T2D.