Recent Submissions

  • Current Trends in the Duration of Anticoagulant Therapy for Venous Thromboembolism: A Systematic Review

    Alexander, Peter; Visagan, Shakthi; Issa, Reem; Gorantla, Vasavi Rakesh; Thomas, Sneha E (Cureus, Inc., 2021-10-23)
    Anticoagulation therapy is the first line and drug of choice for both the treatment and prophylaxis of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism). Anticoagulation drugs, ranging from different preparations of heparin, warfarin, and newer direct oral drugs such as rivaroxaban and dabigatran, work mainly by inhibiting important factors and enzymes in the coagulation cascade by preventing fibrin formation, platelet aggregation, and clot assembly. With recurrent thrombosis and embolisms being a feared complication for many physicians treating such cases, anticoagulation is often extended beyond the initial three- to six-month acute phase after an incident of venous thromboembolism. For some groups of patients, anticoagulation needs to be offered indefinitely to decrease the risk of a recurrent thrombosis. However, this concomitantly increases obvious and dangerous adverse effects such as increased risk of hemorrhage, as the ability to clot is hindered. This tradeoff between recurrent venous thromboembolism and bleeding is what underscores the controversy of the clinical question: for how long should anticoagulation be administered for venous thromboembolism? This review analyzes the use of anticoagulants in different types of venous thromboembolism and remarks on current consensus and trends on the length of anticoagulation treatment. We are doing so while acknowledging that venous thromboembolism management is an active area of research that is rapidly evolving. A literature search was performed looking at recent studies on anticoagulant administration for the treatment of venous thromboembolism with a focus on varying durations and patient populations. Factors that affect clinical decisions of duration are also elucidated. The most clinically relevant anticoagulants were discussed and their effects on the risk of recurrent thrombosis and embolism, and the risk of bleeding in relation to other drugs were analyzed. Ultimately, this article discussed patterns of anticoagulant treatments duration and which patient groups are likely to benefit the most from certain durations, shedding light on the ambiguity in how physicians should approach administering anticoagulation therapy over time for a broad range of presentations of venous thromboembolism.
  • Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children

    Gordon, Oren; Brosnan, Mary Katherine; Yoon, Steve; Jung, Dawoon; Littlefield, Kirsten; Ganesan, Abhinaya; Caputo, Christopher A; Li, Maggie; Morgenlander, William R; Henson, Stephanie N; et al. (American Society for Clinical Investigation, 2021-12-02)
    Background: While most children experience mild COVID-19, high-risk children with underlying conditions may develop severe disease, requiring interventions. Kinetics of antibodies transferred via COVID-19 convalescent plasma early in disease, have not been characterized. Methods: In this study (NCT04377672), high-risk children were prospectively enrolled to receive high-titer COVID-19 convalescent plasma (>1:320 anti-spike IgG; Euroimmun). Passive transfer of antibodies and endogenous antibody production were serially evaluated for up to 2 months after transfusion. Commercial and research ELISA assays, virus neutralization assays, high-throughput phage-display assay utilizing a coronavirus epitope library and pharmacokinetic analyses were performed. Results: Fourteen high-risk children (median age 7.5 years) received high-titer COVID-19 convalescent plasma, nine children within five days (range 2-7) of symptom onset and five children within 4 days (range 3-5) after exposure to SARS-CoV-2. There were no serious adverse events related to transfusion. Antibodies to SARS-CoV-2 were transferred from the donor to the recipient, but antibody titers declined by 14-21 days with a 15.1-day t½ for spike protein IgG. Donor plasma had significant neutralization capacity which was transferred to the recipient. However, as early as 30 minutes post-transfusion, recipient plasma had low neutralization capacity. Conclusions: Convalescent plasma transfused to high-risk children appears to be safe with expected antibody kinetics, regardless of weight or age. However, current use of convalescent plasma in high-risk children achieves low neutralizing capacity.
  • Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking.

    Piacentino, Daria; Grant-Beurmann, Silvia; Vizioli, Carlotta; Li, Xiaobai; Moore, Catherine F; Ruiz-Rodado, Victor; Lee, Mary R; Joseph, Paule V; Fraser, Claire M; Weerts, Elise M; et al. (Springer Nature, 2021-12-01)
    A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p's < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p's < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.
  • The Impact of COVID-19 on Pediatric Telepsychiatry Training in Child and Adolescent Psychiatry Fellowships

    DeJong, Sandra M; Brooks, Deborah; Khan, Shabana; Reaves, Samantha; Busch, Bianca; Alicata, Dan; Ramtekkar, Ujjwal; Vo, Lan Chi; Pruitt, David (Springer Nature, 2021-12-02)
    Objective: This report summarizes findings from a 2020 survey of US child and adolescent psychiatry training programs that explored the impact of the COVID-19 pandemic on pediatric telepsychiatry training. The authors hypothesized that telepsychiatry training significantly increased during the pandemic, in part due to legal and regulatory waivers during the COVID-19 public health emergency. Methods: In August 2020, an anonymous, 28-question online survey was emailed to all (138) accredited child psychiatry fellowships on the Accreditation Council for Graduate Medical Education website. Forty-nine programs responded (36%). This analysis focuses on three of the 28 questions relevant to the hypotheses: characteristics of the program's training in telepsychiatry; perceived impediments to clinical training; and perceived impediments to didactic training pre-COVID onset vs. post-COVID onset, respectively. Total scores were created to investigate differences in training programs and impediments to including telepsychiatry pre- and post-COVID onset. Paired sample t-tests were used to compare means pre- and post-COVID onset. Results: Results provided support for significant differences between training components related to telepsychiatry pre- and post-COVID onset, with participants reporting more training components post-COVID onset (M = 5.69) than pre-COVID onset (M = 1.80); t(48) = 9.33, p < .001. Participants also reported significantly fewer barriers to providing clinical experiences in pediatric telepsychiatry post-COVID onset (M = 2.65) than pre-COVID onset (M = 4.90); t(48) = - 4.20, p < .001. Conclusions: During the COVID-19 pandemic, pediatric telepsychiatry training in child psychiatry fellowships increased significantly. Perceived barriers to providing clinical, but not didactic, training decreased significantly.
  • Attitudes among healthcare professionals towards cardiopulmonary resuscitation during COVID-19

    Al-Shiakh, Safinaz; Tran, Quincy K; Caggiula, Amy; Berezowski, Ivan; Barnawi, Basma; Pourmand, Ali (Elsevier Inc., 2021-11-15)
    Background: Out-of-hospital cardiac arrests (OHCAs) are a leading cause of mortality in the United States. The ongoing COVID-19 pandemic has dramatically altered the landscape of response to OHCAs, particularly with regard to providing cardiopulmonary resuscitation (CPR). We aimed to describe, characterize, and address the attitudes and concerns of healthcare workers towards CPR of OHCA patients during the COVID-19 pandemic. Methods: We performed a cross-sectional study of healthcare workers and trainees in the United States and Saudi Arabia via an online survey available between October 2020, and May 2021. The primary outcome of interest was willingness to perform CPR for OHCA, with confidence to handle CPR for OHCA as our secondary outcome. Results: A total of 501 healthcare professionals, including 436 (87%) with background in emergency medicine, participated in our survey. 331 (66%) reported being willing to perform CPR for OHCA, while 170 (34%) were not willing. 311 (94%) willing participants stated that their medical oath and moral responsibility were the main motivators for willingness, while a fear of contracting COVID-19 was the primary demotivating factor for 126 (74%) unwilling participants. Time series analysis with simple exponential smoothing showed an increase in willingness to perform CPR from 30% to 50%, as well as an increase in mean confidence level to perform CPR from 60% to 70%, between October 2020 and May 2021. Conclusions: The ongoing COVID-19 pandemic significantly affected healthcare workers' attitudes towards performing CPR for OHCA. Confidence levels and willingness to perform CPR increased over time during the study period. Efforts should be directed towards the creation of standardized and evidence-based guidelines for CPR during COVID-19, as well as increasing knowledge regarding risks of infection and effective use of PPE during resuscitation.
  • Rolf Neth (October 6, 1926 to March 17, 2020)

    Hehlmann, Rüdiger; Gallo, Robert; Hoelzer, Dieter; Welte, Karl; Gale, Robert Peter; Zander, Axel (Springer Nature, 2020-06-01)
  • Rapid and Noninvasive Quantification of Capsid Gene Filling Level Using Water Proton Nuclear Magnetic Resonance

    Taraban, Marc B.; Jones, Michael T.; Yu, Yihua Bruce (American Chemical Society, 2021-11-18)
    The present work reports an enabling novel technology for quantifying the gene content in adeno-associated viral capsids. The method is based on the water proton nuclear magnetic resonance (wNMR) technique. Instead of analyzing the capsid directly, it utilizes water molecules to distinguish empty and full capsids, as water interacts with them differently. The transverse relaxation rate of water protons, R2(1H2O), readily distinguishes empty and full capsids and is capable of quantifying the fraction of full capsids in a mixture of full and empty ones. It involves no sample preparation and no reagents. Measurement is rapid (data collection takes 1-2 min), noninvasive (the capsid sample can stay inside the original sealed and labeled container to be used in other studies or administered to a patient), and performed using a wide-bore benchtop NMR instrument. The method can be readily implemented at a production plant for product release as part of product quality control. © 2021 American Chemical Society.
  • Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study

    Wang, Zhanwei; Budhu, Anuradha S.; Shen, Yi; Wong, Linda Lou; Hernandez, Brenda Y.; Tiirikainen, Maarit; Ma, Xiaomei; Irwin, Melinda L.; Lu, Lingeng; Zhao, Hongyu; et al. (Wiley-Blackwell, 2021-11-27)
    Background and Aim: Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS). Methods: Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results: In this GWAS, we found that two SNPs were associated with HCC at P < 5E-8 and six SNPs at P < 5E-6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case-control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta-analysis of multiple datasets indicated that these SNPs were significantly associated with HCC. Conclusions: SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated. © 2021 The Authors.
  • Revisiting Pauwels' Classification Of Femoral Neck Fractures

    Nand, Sumon (Baishideng Publishing Group Co, 2021-11-18)
    Pauwels’ femoral neck fracture classification is based on the biomechanical principle that shear stress and varus force increase along more vertically oriented fractures, resulting in higher risk of fracture displacement and ultimately nonunion. This principle continues to guide construct selection for femoral neck fracture internal fixation and is the foundation for treating non-union with valgus osteotomy. However, with poor inter- and intra-rater reliability, dated treatment recommendations, and unreliable prognostic value, the Pauwels classification cannot be directly applied in its entirety to the management of femoral neck fractures in modern practice. © 2021. Published By Baishideng Publishing Group Inc. All Rights Reserved
  • Behavior of motor units during submaximal isometric contractions in chronically strength-trained individuals

    Casolo, Andrea; Del Vecchio, Alessandro; Balshaw, Thomas G.; Maeo, Sumiaki; Lanza, Marcel Bahia; Felici, Francesco; Folland, Jonathan P.; Farina, Dario (American Physiological Society, 2021-10-07)
    Neural and morphological adaptations combine to underpin the enhanced muscle strength following prolonged exposure to strength training, although their relative importance remains unclear. We investigated the contribution of motor unit (MU) behavior and muscle size to submaximal force production in chronically strength-trained athletes (ST) versus untrained controls (UT). Sixteen ST (age: 22.9 ± 3.5 yr; training experience: 5.9 ± 3.5 yr) and 14 UT (age: 20.4 ± 2.3 yr) performed maximal voluntary isometric force (MViF) and ramp contractions (at 15%, 35%, 50%, and 70% MViF) with elbow flexors, whilst high-density surface electromyography (HDsEMG) was recorded from the biceps brachii (BB). Recruitment thresholds (RTs) and discharge rates (DRs) of MUs identified from the submaximal contractions were assessed. The neural drive-to-muscle gain was estimated from the relation between changes in force (DFORCE, i.e. muscle output) relative to changes in MU DR (DDR, i.e. neural input). BB maximum anatomical cross-sectional area (ACSAMAX) was also assessed by MRI. MViF (+64.8% vs. UT, P < 0.001) and BB ACSAMAX (+71.9%, P < 0.001) were higher in ST. Absolute MU RT was higher in ST (+62.6%, P < 0.001), but occurred at similar normalized forces. MU DR did not differ between groups at the same normalized forces. The absolute slope of the ΔFORCE - ΔDR relationship was higher in ST (+66.9%, P = 0.002), whereas it did not differ for normalized values. We observed similar MU behavior between ST athletes and UT controls. The greater absolute force-generating capacity of ST for the same neural input demonstrates that morphological, rather than neural, factors are the predominant mechanism for their enhanced force generation during submaximal efforts. © 2021 American Physiological Society. All rights reserved.
  • Macrophage activation in the dorsal root ganglion in rats developing autotomy after peripheral nerve injury

    Xu, Xiang; Zhou, Xijie; Du, Jian; Liu, Xiao; Qing, Liming; Johnson, Blake N.; Jia, Xiaofeng (MDPI AG, 2021-11-26)
    Autotomy, self‐mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to inves-tigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macro-phage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macro-phages were concentrated around NF200‐labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macro-phages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy. © 2021 by the authors.
  • HIV indirectly accelerates coronary artery disease by promoting the effects of risk factors: longitudinal observational study

    Kolossváry, Márton; Celentano, David; Gerstenblith, Gary; Bluemke, David A; Mandler, Raul N; Fishman, Elliot K; Bhatia, Sandeepan; Chen, Shaoguang; Lai, Shenghan; Lai, Hong (Springer Nature, 2021-11-30)
    Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and—uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ± 0.8/year vs. 0.5 ± 1.3/year, p = 0.96). Multivariately, HIV-infection was not associated with Agatston-scores (8.3, CI: [− 37.2–53.7], p = 0.72), the number of coronary plaques (− 0.1, CI: [− 0.5–0.4], p = 0.73) or SSS (− 0.1, CI: [− 1.0–0.8], p = 0.84). ASCVD risk scores and years of cocaine-use significantly increased all CAD outcomes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles. However, HIV-infection may indirectly promote CAD progression as risk factors may have a more prominent role in the acceleration of CAD in these patients. © 2021, The Author(s).
  • Social capital during the first wave of the covid-19 outbreak: The case of the island of menorca

    Villalonga-Olives, Ester; Kawachi, Ichiro; Hernández-Aguado, Ildefonso (MDPI AG, 2021-12-02)
    The rapidly evolving coronavirus pandemic has drastically altered the economic and social lives of people throughout the world. Our overall goal is to understand the mechanisms through which social capital shaped the community response to the pandemic on the island of Menorca, Spain, which was under a strict lockdown in 2020. Between April and June 2020, we performed qualitative interviews (n = 25) of permanent residents of the island. From the findings, it is evident that social capital is an important resource with the capacity to organize help and support. However, the dark sides of social capital, with lack of social cohesion and lack of trust, also emerged as an important negative issue. We identified sources of tension that were not resolved, as well as important sociodemographic differences that are primary drivers for health inequalities. The investment in social networks and social capital is a long-term need that should consider sociodemographic vulnerability. © 2021 by the authors.
  • Phenobarbital induces slc13a5 expression through activation of pxr but not car in human primary hepatocytes

    Li, Zhihui; Li, Linhao; Heyward, Scott; Men, Shuaiqian; Xu, Meishu; Sueyoshi, Tatsuya; Wang, Hongbing (MDPI AG, 2021-12-01)
    Phenobarbital (PB), a widely used antiepileptic drug, is known to upregulate the expression of numerous drug-metabolizing enzymes and transporters in the liver primarily via activation of the constitutive androstane receptor (CAR, NR1I3). The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter, plays an important role in intracellular citrate homeostasis that is associated with a number of metabolic syndromes and neurological disorders. Here, we show that PB markedly elevates the expression of SLC13A5 through a pregnane X receptor (PXR)dependent but CAR-independent signaling pathway. In human primary hepatocytes, the mRNA and protein expression of SLC13A5 was robustly induced by PB treatment, while genetic knockdown or pharmacological inhibition of PXR significantly attenuated this induction. Utilizing genetically modified HepaRG cells, we found that PB induces SLC13A5 expression in both wild type and CARknockout HepaRG cells, whereas such induction was fully abolished in the PXR-knockout HepaRG cells. Mechanistically, we identified and functionally characterized three enhancer modules located upstream from the transcription start site or introns of the SLC13A5 gene that are associated with the regulation of PXR-mediated SLC13A5 induction. Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR. Collectively, these data reveal PB as a potent inducer of SLC13A5 through the activation of PXR but not CAR in human primary hepatocytes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
  • Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis

    Wang, Sheng; Yang, Yang; Suen, Andrew; Zhu, Jing; Williams, Brittney; Hu, Jiang; Chen, Fengqian; Kozar, Rosemary; Shen, Shiqian; Li, Ziyi; et al. (Elsevier Inc., 2021-11-13)
    Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis. © 2021 The Author(s)
  • Wohlfahrtiimonas chitiniclastica monomicrobial bacteremia in a homeless man

    Harfouch, Omar; Luethy, Paul M.; Noval, Mandee; Baghdadi, Jonathan D. (Centers for Disease Control and Prevention (CDC), 2021-11-04)
    We report a case of septic shock attributable to monomicrobial bloodstream infection secondary to Wohlfahrtiimonas chitiniclastica infection. This case suggests that W. chitiniclastica likely possesses the virulence to cause severe disease. Culture-independent techniques were essential in the identification of this organism, which enabled selection of appropriate therapy. © 2021 Centers for Disease Control and Prevention (CDC). All rights reserved.
  • Meeting the challenges of retention and enrollment of study participants in clinical trials during the COVID-19 pandemic from the study leadership perspective: Experience from the Zoster Eye Disease Study (ZEDS)

    Tom, MeeLee; Cohen, Elisabeth J; LopezJimenez, Carlos; Hochman, Judith S; Troxel, Andrea B; Jeng, Bennie H (Elsevier B.V., 2021-11-16)
    Purpose: To describe steps taken that enabled a high rate of retention and early resumption of enrollment in the Zoster Eye Disease Study (ZEDS), a randomized controlled trial funded by the National Eye Institute, during the first 13 months (3/1/2020-3/31/2021) of the COVID-19 pandemic. Methods: A number of responses were implemented in ZEDS when the focus shifted to retention of study participants at the beginning of the pandemic including frequent communication with the participating clinical centers (PCCs) about remote visits, local lab work, shipping study medication, and completion of revised case report forms. Additional payments were provided to the PCCs. Remote activation of PCCs continued. Screening and enrollment visits gradually resumed when allowed. Results: Communication with PCCs increased, and average attendance at monthly coordinator teleconferences went up from 17 to 47. Remote visits peaked in April 2020, accounting for 75% (33/44) of study visits, then declined to less than 10% of study visits beginning August 2020. Overall, 97% (590/609) of study visits were completed. Only 5.5% (9/165) of study participants withdrew consent, and 2.4% (4/165) were lost to follow-up. Enrollment returned to pre-pandemic levels by September 2020. Discussion: Strong communication and unwavering commitment, combined with the technological capability for remote work, visits, and shipment of study medication, were key to the successful retention of study participants and resumption of enrollment. Conclusions: Rapid responses to challenges to trials caused by the COVID-19 pandemic can enable them to continue successfully and provide insights into the planning of future trials.
  • Acute on Chronic Liver Failure: Factors Associated With Transplantation

    Goussous, Naeem; Xie, Wen; Zhang, Talan; Malik, Saad; Alvarez-Casas, Josue; Gray, Stephen H; Barth, Rolf N; Thuluvath, Paul J; LaMattina, John C (Wolters Kluwer Health, 2021-11-17)
    Background: Acute on chronic liver failure (ACLF) carries a poor prognosis unless liver transplantation is offered. We present risk factors associated with proceeding with liver transplantation in patients with ACLF. Methods: A retrospective review of all patients with ACLF who presented to a single transplant center between January 2016 and December 2017 was performed. We compared patients who were transplanted with patients who were not. Results: During the study period, 144 patients with ACLF were identified, 86 patients (59.7%) were transplanted, and 58 were not. The transplanted patients had a lower number of failed organs (4 versus 5, P < 0.001) and lower incidence of ACLF grade 3 (76.7% versus 94.8%, P = 0.014) compared with nontransplanted patients. Liver transplantation offered a 1-y survival of 86% as compared to 12% in the nontransplanted group. Hospital charges were significantly higher among transplanted patients as compared with the nontransplanted patients ($227 886 versus $88 900, P < 0.001). Elevated serum lactate was a risk factor in not offering liver transplantation in ACLF patients. Conclusions: In appropriately selected patients with ACLF, liver transplantation is feasible and can provide above 86% 1-y patient survival even in grade 3 ACLF.
  • Development of a Culturally Sensitive Asian American/Pacific Islander Curriculum for Child Psychiatry Trainees.

    Han, Crystal; Chou, Shinnyi; Shaligram, Deepika; Chan, Vivien; Song, Suzan; Edwards, Sarah; Gordon-Achebe, Kimberly (Springer Nature, 2021-11-19)

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