bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic Events in COVID-19 Patients Undergoing Convalescent Plasma Therapy: A Systematic Review
Authors: Yu Philip , Khalid Faran , Li Allen , Laureano Marissa , Crowther Mark 
Published: November 2021

Abstract
INTRODUCTION
Convalescent plasma therapy (CPT) has been proposed as a mechanism of passive immunization against COVID-19. Current guidelines on the efficacy of its use is not well delineated with limited studies analyzing the risk of thromboembolic events during treatment. The goal of this systematic review and meta-analysis was to assess the risk of arterial and venous thromboembolisms from CPT in patients with COVID-19.
METHODS
We conducted a comprehensive literature review of Ovid MEDLINE, Cochrane Central Registry of Controlled Trials (CENTRAL), and EMBASE from inception to June 2021. Title and abstract screening and full-text screening was done in duplicate by two independent reviewers. All randomized controlled trials and cohort studies that analyzed adult COVID-19 patients undergoing CPT were included for analysis. Editorials, conference abstracts, narrative reviews, case series, containing less than 100 patients were excluded. The primary outcome analyzed was the risk of thrombotic events in CPT + standard therapy vs standard therapy alone. Meta-analysis was done using a random-effects model using the Revman 5 software.
RESULTS
Of 1774 studies identified from our search, three randomized (n= 660 patients), and one non-randomized matched cohort study) (n = 96 patients) were included for analysis. The risk ratio for thrombotic events was 2.33, favoring the CPT group (95% CI, [0.70, 7.72], P = 0.17, I2 = 29%). Subgroup analyses showed that CPT + standard therapy was associated with a decreased risk of in-hospital mortality (RR = 0.70 [0.49, 0.98], P = 0.04, I2 = 0%). No significant difference in cardiovascular events (RR = 0.90 [0.67, 1.20], P = 0.48, I2 = 0%), hypertension (RR = 1.67 [0.56, 4.98], P = 0.35, I2 = 0%), and septic shock (RR = 0.97 [0.40, 2.35], P = 0.94, I2 = 41%) was found between CPT + standard therapy and standard therapy alone.
CONCLUSION
We found treatment of COVID-19 with standard therapy + CPT was not associated with an increase in the risk of thromboembolic events. CPT was associated with a decreased risk of in-hospital mortality but not of MACE, hypertension, or septic shock.

Disclosures
Crowther: Hemostasis reference laboratories: Honoraria; Bayer: Speakers Bureau; CSL Behring: Speakers Bureau; Precision Biologicals: Honoraria; Pfizer: Speakers Bureau; Syneos Health: Honoraria.
Epidemiology of Hospitalizations Due to Autoimmune Hemolytic Anemia in the United States
Authors: Mullangi Sanjana , Yadav Preeti , Kilinc Ekim , Gudivada Silpa , Khan Javaria , Anumolu Prathyusha , Khadka Shushmita , Goswami Ruchir , Patel Achint , Welaya Karim , Lekkala Manidhar Reddy 
Published: November 2021

Abstract
Introduction:
Autoimmune hemolytic anemia (AIHA) is an acquired immune disorder resulting in the production of cold and warm autoantibodies directed against red blood cell antigens; characterized by shortened red blood cell survival and a positive Coombs test. Types include primary disease (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immunosuppression with corticosteroids and other agents, Transfusion. There is not much recent data available on epidemiology of AIHA. We aim to estimate epidemiological trends and outcomes of AIHA as well as factors associated with poor outcomes by using the largest available national database from the United States.
Methods:
We derived a study cohort from the National Inpatient Sample (NIS) for the years 2007-2018 for hospitalizations due to AIHA by using International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes ICD-9-CM/ICD-10-CM). Other diagnosis and comorbidities were also identified by ICD-9/10-CM codes and Elixhauser comorbidity software. Our primary outcome was discharge disposition following AIHA hospitalization. We utilized multivariable survey logistic regression models to analyze and identify predictors of poor outcomes.
Results:
Between 2007-2018, a total of 52,814 hospitalizations occurred due to primary diagnosis of AIHA. Burden of hospitalizations remained stable from 4,254 (8.1%) in 2007 to 4,405 (8.3%) in 2018. AIHA patients in the study cohort were mostly above 65 years of age (48.6%) followed by 35-65 years of age (33.7%), females (58.3%) and Caucasians (69.1%). Overall in-hospital mortality of AIHA hospitalizations was 3.1%, and discharge to facility was 11.86%. Median length of stay for AIHA hospitalization was 4-days (interquartile range: 2-days to 6-days). Furthermore, in multivariable logistic regression analysis, increasing age (OR 1.2; 95%CI 1.1-1.3; p&lt;0.001), male gender (OR 1.5; 95%CI 1.2-1.3; p:0.0024), vascular events (OR 1.5 ; 95%CI 1.1-2.0; p:0.0156), teaching hospitals (OR 3.1; 95%CI 1.5-6.5; p:0.002), plasmapheresis (OR 5.5; 95%CI 2.8-10.8; p:0.001) and intravenous immunoglobulins (OR 1.9; 95%CI 1.3-3.0; p:0.001) were associated with higher in-hospital mortality.
Conclusion:
Our study describes the epidemiology of hospitalizations due to AIHA in the United States from a nationally representative database. We observed that hospitalization burden due to AIHA have remained stable from 2007 to 2018. We also identified factors associated with higher in-hospital mortality and some of which are modifiable. Further studies are required to establish the causal association of these factors to poor outcomes and develop better risk stratification strategies to improve overall outcomes of AIHA.

Disclosures
No relevant conflicts of interest to declare.
Two Stage Intravital Imaging Mouse Model to Assess Venous Thromboembolism in Sickle Cell Disease
Authors: Brzoska Tomasz , Kaminski Tomasz W. , Tutuncuoglu Egemen , Gladwin Mark T. , Sundd Prithu 
Published: November 2021

Abstract
Sickle cell disease (SCD) patients have an increased risk of venous thromboembolism (VTE). Population-based studies demonstrated that VTE has a cumulative incidence rate of approximately 25% in adult SCD patients and is associated with higher risk of mortality. VTE in SCD is most commonly manifested as deep vein thrombosis (DVT) with associated pulmonary embolism (PE). Although autopsy studies have regularly discovered pulmonary thromboembolic lesions in SCD patients, the pathophysiology of VTE in SCD remains largely unknown mostly due to the lack of relevant animal VTE model. Understanding the mechanisms that promote VTE in SCD is imperative to identify its prevention and treatment measures.
To elucidate the cellular, molecular and biophysical mechanisms of VTE in SCD we developed an innovative two stage intravital imaging analysis experimental model in SCD mice. DVT in SCD mice was induced by surgical ligation of femoral vein. Venous thrombus formation was visualized using intravital multi-photon-excitation (MPE) microscopy. Venous thrombus took the form of a large mass of elliptical shape which extended in the long-axis direction of the femoral vein. It was composed of fibrin, erythrocytes and sparse platelets. Over time, thrombus was infiltrated by migrating neutrophils. To trigger acute PE, femoral vein ligation was removed and the venous thrombus was observed to spontaneously detach and travel to the SCD mouse lung. This method allowed real time visualization of acute PE in vivo using MPE microscopy of intact lung in live breathing mice. Acute PE involved embolization of the pulmonary arterioles and the arteriolar bottle-necks located at the junction of pulmonary arterioles and capillaries. The embolization of arteriolar circulation led to loss of blood flow in the arterioles and the down-stream capillaries.
Herein we introduce an intravital microscopy approach to probe VTE in SCD live mouse. Our model has potential application in investigating the molecular determinants of VTE associated with SCD as well as evaluating efficacy of new antithrombotic drugs.

Disclosures
Sundd: Bayer: Research Funding; CSL Behring Inc: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.
Implementation of a High-Dose Cytarabine Outpatient Program for Acute Myeloid Leukemia Patients in a Limited-Source Setting
Authors: Haro Juan C , Espinoza-Morales Evelyn , Espino Johan , Jiménez-Mozo Fátima , Poma Nathaly , Casas Jhoisy , Castro-Mollo Melanie , Sandival Gustavo , Ortega Emperatriz , Roque Katia , Lopez Lourdes , Alcarraz Cindy , Lozano Sophia , Cervantes Elizabeth , Quintana Shirley , Vidaurre Tatiana , Enriquez Daniel J 
Published: November 2021

Abstract
Background: The management of acute myeloid leukemia (AML) patients usually requires long inpatient treatments that can affect the limited care facilities, the quality of life, and increases healthcare costs. Additionally, leukemia treating centers in developing countries face limited sources to deliver high-dose chemotherapies as inpatient treatments. Therefore, several reports have established the feasibility and safety of outpatient consolidation. We aimed to implement a high-dose cytarabine outpatient program for AML in a limited-source institution at a public center in Peru.Methods: We conducted a prospective pilot study starting in January 2019 and ending before the COVID-19 Pandemic in March 2020. Eligible patients were ≥ age 14, met inclusion criteria for inpatient induction regimens, were without active infection, and had the following: normal chest x-ray and biochemistry, complete remission after one cycle of 7+3 induction. Logistical requirements included a 3-hours distance residence near the treatment center, caregiver support, trained nursing staff, infusion room capacity, and participation in follow-up. Patients received prophylactic antimicrobials such as oral levofloxacin, fluconazole, and acyclovir and were admitted to the hospital for predetermined complications of therapy (fever, G3-4 toxicity, febrile neutropenia, bleeding or refractory thrombocytopenia). Risk stratification was based on conventional cytogenetics and multiplex PCR using Leukemia.net criteria.
Results: Forty-two patients were included during the study period. The median age was 38 years (16-63) and Female/Male ratio 4:3. According to Leukemia.net, 24% were classified as high, 50% intermediate and 26% as low risk group. Including FLT3 mutations in 26% of cases. Twenty-two and 20 subjects received 1-2 and 3-4 cycles of ambulatory HiDAC, respectively. About one-third of cases had emergency admissions during consolidation and 74% complete at least 3 cycles of cytarabine. Only 4 patients underwent sibling-donor allo-SCT. Sixty-four percent experienced relapses, and at 2 years follow-up only 21 subjects were alive. Median OS was 15 months, a better survival was shown among patients who received 3-4 cycles of ambulatory HiDAC (2-year OS 18 vs 23%, p=0.031).
Conclusion: Our pilot study shows the feasibility to deliver HiDAC as outpatient consolidation in selected AML cases in a limited setting. Additionally, a high rate of relapses and poor survival was noted in our cohort that requires further consideration.

Disclosures
No relevant conflicts of interest to declare.
Performance of Neutrophil-to-Lymphocyte Ratio (NLR) in Differentiating Vaso-Occlusive Crisis from Infection in Patients Presenting with Sickle Cell Crisis
Authors: Maharaj Satish , Chang Simone M , Xue Ruobing , Cisak Kamila I. , Sharma Vivek R. 
Published: November 2021

Abstract
Background:
Patients with sickle cell disease (SCD) are at increased risk of developing serious infections as a result of functional asplenia and altered humoral immunity. Nevertheless, presenting symptoms of sepsis such as fever and arthralgias are common in SCD and can occur with many sickle cell related conditions, including vaso-occlussive crises (VOC) and may not correlate with true infections. The neutrophil-to-lymphocyte ratio (NLR) is calculated as the absolute neutrophil count divided by the absolute lymphocyte count and represents an easily accessible value that has been found to correlate with inflammation and prognosis in several conditions. Few studies have evaluated NLR as a biomarker in sickle cell disease, and its utility in differentiating infection vs. VOC in patients presenting to the emergency room remains unknown.
Method: We conducted a retrospective review of 143 patients with SCD who presented to the emergency department with fever and painful crises. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=92) and patients with proven/possible infection (n=51). Inclusion criteria for both groups were patients with SCD, 17 years and older and complete blood count with differential on presentation; patients who had received antibiotics prior to presentation were excluded. Data collected on presentation included genotype, age, gender, complete blood count, hydroxyurea use. Data was analyzed between the two groups using descriptive statistics and receiver-operating characteristic (ROC) curve analysis.
Results: Demographics and clinical characteristics are summarized in the Table. The sample included primarily young adult males with 61% on hydroxyurea. Genotype HbSS (73%) was most prevalent followed by HbSC (23%) and HbSβ (4%). The mean Hb was around 8 g/dL. The VOC group had a lower mean white blood cell (WBC) count of 13.6, compare to 17.2 for patients with proven/possible infection. ROC analysis showed that NLR did correlate with infection, with a modest AUC 0.7 [95% CI (0.59-0.77)] that was significant (p=0.0002) when compared to the AUC=0.5 model. Maximum specificity and sensitivity in this sample was achieved with NLR = 4.5 (Specificity 75% and Sensitivity 59%).
Conclusion: In this sample, NLR on presentation significantly but only modestly correlated with infection as opposed to VOC. Optimal performance at NLR=4.5 achieved Specificity 75% and Sensitivity 59%. Despite modest performance, given the widespread availability and cost-effectiveness of NLR testing, further study in a larger sample may derive other variables that can combine with NLR to formulate a predictive model to improve care for these patients.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Evaluating the performance of propensity score matching based approaches in individual patient data meta-analysis
Authors: Johara Fatema Tuj , Benedetti Andrea , Platt Robert , Menzies Dick , Viiklepp Piret , Schaaf Simon , Chan Edward 
Published: November 2021

Abstract
Background
Individual-patient data meta-analysis (IPD-MA) is an increasingly popular approach because of its analytical benefits. IPD-MA of observational studies must overcome the problem of confounding, otherwise biased estimates of treatment effect may be obtained. One approach to reducing confounding bias could be the use of propensity score matching (PSM). IPD-MA can be considered as two-stage clustered data (patients within studies) and propensity score matching can be implemented within studies, across studies, and combining both.

Methods
This article focuses on implementation of four PSM-based approaches for the analysis of data structure that exploit IPD-MA in two ways: (i) estimation of propensity score model using single-level or random-effects logistic regression; and (ii) matching of propensity scores (PS) across studies, within studies or preferential-within studies. We investigated the performance of these approaches through a simulation study, which considers an IPD-MA that examined the success of different treatments for multidrug-resistant tuberculosis (MDR-TB). The simulation parameters were varied according to three treatment prevalences (according to studies, 50% and 30%), three levels of heterogeneity between studies (low, moderate and high) and three levels of pooled odds ratio (1, 1.5, 3).

Results
All approaches showed greater biases at the higher levels of heterogeneity regardless of the choices of treatment prevalences. However, matching of propensity scores using within-study and preferential-within study reported better performance compared to matching across studies when treatment prevalence varied across-studies. For fixed prevalences, a random-effect propensity score model to estimate propensity scores followed by matching of propensity scores across-studies achieved lower biases compared to other PSM-based approaches.

Conclusions
Propensity score matching has wide application in health research while only limited literature is available on the implementation of PSM methods in IPD-MA, and until now methodological performance of PSM methods have not been examined. We believe, this work offers an intuition to the applied researcher for the choice of the PSM-based approaches.
Effect of the “Normalized Epidemic Prevention and Control Requirements” on hospital-acquired and community-acquired infections in China
Authors: Chen Caiyun , Zhu Ping , Zhang Yongxiang , Liu Bo 
Published: November 2021

Abstract
Background
No studies have yet reported the effect of prevention and control measures, which were implemented to combat COVID-19, on the prevention and control of common HAIs. We aimed to examine the effect of the “Normalized Epidemic Prevention and Control Requirements” (implemented in May 2020) by comparison of hospital-acquired infections (HAIs) and community-acquired infections (CAIs) in China during 2018, 2019, and 2020.

Methods
Data of inpatients before and after implementation of new requirements were retrospectively analyzed, including infection rate, use of alcohol-based hand cleaner, anatomical sites of infections, pathogen species, infection by multi-drug resistant species, and use of different antibiotics.

Results
The HAI rate was significantly higher in 2020 than in 2018 and 2019 (P < 0.05), and the CAI rate was significantly higher in 2019 and 2020 than in 2018 (P < 0.001). Lower respiratory tract infections were the most common HAI during all years, with no significant changes over time. Lower respiratory tract infections were also the most common CAI, but were significantly more common in 2018 and 2019 than 2020 (P < 0.001). There were no changes in upper respiratory tract infections among HAIs or CAIs. Most HAIs and CAIs were from Gram-negative bacteria, and the percentages of fungal infections were greater in 2019 and 2020 than 2018. MRSA infections were more common in 2020 than in 2018 and 2019 (P < 0.05). The utilization rate and usage days of antibiotics decreased over time (P < 0.001) and the culture rate of microbial specimens before antibiotic usage increased over time (P < 0.001).

Conclusions
The new prevention and control requirements provided important benefits during the COVID-19 pandemic. However, their effects on HAIs were not obvious.
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
Authors: Hutchison R. Matthew , Evans Karleyton C. , Fox Tara , Yang Minhua , Barakos Jerome , Bedell Barry J. , Cedarbaum Jesse M. , Brys Miroslaw , Siderowf Andrew , Lang Anthony E. 
Published: November 2021

Abstract
Background
Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood.

Methods
The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis.

Results
In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]).

Conclusion
A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects.

Trial registration
ClinicalTrials.gov identifier: NCT03318523.
Date submitted: October 19, 2017.
First Posted: October 24, 2017.
Urban-rural differences in the associated factors of severe under-5 child undernutrition based on the composite index of severe anthropometric failure (CISAF) in Bangladesh
Authors: Anik Asibul Islam , Chowdhury Mohammad Rocky Khan , Khan Hafiz T. A. , Mondal Md Nazrul Islam , Perera Nirmala K. P. , Kader Manzur 
Published: November 2021

AbstractIntroductionSevere undernutrition among under-5 children is usually assessed using single or conventional indicators (i.e., severe stunting, severe wasting, and/or severe underweight). But these conventional indicators partly overlap, thus not providing a comprehensive estimate of the proportion of malnourished children in the population. Incorporating all these conventional nutritional indicators, the Composite Index of Severe Anthropometric Failure (CSIAF) provides six different undernutrition measurements and estimates the overall burden of severe undernutrition with a more comprehensive view. This study applied the CISAF indicators to investigate the prevalence of severe under-5 child undernutrition in Bangladesh and its associated socioeconomic factors in the rural-urban context.MethodsThis study extracted the children dataset from the 2017–18 Bangladesh Demographic Health Survey (BDHS), and the data of 7661 children aged under-5 were used for further analyses. CISAF was used to define severe undernutrition by aggregating conventional nutritional indicators. Bivariate analysis was applied to examine the proportional differences of variables between non-severe undernutrition and severe undernutrition group. The potential associated socioeconomic factors for severe undernutrition were identified using the adjusted model of logistic regression analysis.ResultsThe overall prevalence of severe undernutrition measured by CISAF among the children under-5 was 11.0% in Bangladesh (rural 11.5% vs urban 9.6%). The significant associated socioeconomic factors of severe undernutrition in rural areas were children born with small birth weight (AOR: 2.84), children from poorest households (AOR: 2.44), and children aged < 36 months, and children of uneducated mothers (AOR: 2.15). Similarly, in urban areas, factors like- children with small birth weight (AOR: 3.99), children of uneducated parents (AOR: 2.34), poorest households (APR: 2.40), underweight mothers (AOR: 1.58), mothers without postnatal care (AOR: 2.13), and children’s birth order ≥4 (AOR: 1.75), showed positive and significant association with severe under-5 undernutrition.ConclusionSevere undernutrition among the under-5 children dominates in Bangladesh, especially in rural areas and the poorest urban families. More research should be conducted using such composite indices (like- CISAF) to depict the comprehensive scenario of severe undernutrition among the under-5 children and to address multi-sectoral intervening programs for eradicating severe child undernutrition.