Now showing items 1-20 of 5162

    • Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

      Dunkle, Lisa M; Kotloff, Karen L; Gay, Cynthia L; Áñez, Germán; Adelglass, Jeffrey M; Barrat Hernández, Alejandro Q; Harper, Wayne L; Duncanson, Daniel M; McArthur, Monica A; Florescu, Diana F; et al. (Massachusetts Medical Society, 2021-12-15)
      Background: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. Methods: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. Results: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. Conclusions: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 number, NCT04611802.).
    • Schizophrenia Patients Show Largely Similar Salience Signaling Compared to Healthy Controls in an Observational Task Environment

      Culbreth, Adam J; Kasanova, Zuzana; Ross, Thomas J; Salmeron, Betty J; Gold, James M; Stein, Elliot A; Waltz, James A (MDPI AG, 2021-12-06)
      Recent evidence suggests that the aberrant signaling of salience is associated with psychotic illness. Salience, however, can take many forms in task environments. For example, salience may refer to any of the following: (1) the valence of an outcome, (2) outcomes that are unexpected, called reward prediction errors (PEs), or (3) cues associated with uncertain outcomes. Here, we measure brain responses to different forms of salience in the context of a passive PE-signaling task, testing whether patients with schizophrenia (SZ) showed aberrant signaling of particular types of salience. We acquired event-related MRI data from 29 SZ patients and 23 controls during the performance of a passive outcome prediction task. Across groups, we found that the anterior insula and posterior parietal cortices were activated to multiple different types of salience, including PE magnitude and heightened levels of uncertainty. However, BOLD activation to salient events was not significantly different between patients and controls in many regions, including the insula, posterior parietal cortices, and default mode network nodes. Such results suggest that deficiencies in salience processing in SZ may not result from an impaired ability to signal salience per se, but instead the ability to use such signals to guide future actions. Notably, no between-group differences were observed in BOLD signal changes associated with PE-signaling in the striatum. However, positive symptom severity was found to significantly correlate with the magnitudes of salience contrasts in default mode network nodes. Our results suggest that, in an observational environment, SZ patients may show an intact ability to activate striatal and cortical regions to rewarding and non-rewarding salient events. Furthermore, reduced deactivation of a hypothesized default mode network node for SZ participants with high levels of positive symptoms, following salient events, point to abnormalities in interactions of the salience network with other brain networks, and their potential importance to positive symptoms.
    • Potential Mechanisms Underlying Hypoxia-Induced Diabetes in a Rodent Model: Implications for COVID-19

      Pae, Eung-Kwon; Harper, Ronald M (MDPI AG, 2021-12-14)
      Previous studies reported that repetitive hypoxia in rat pups reduces insulin secretion and elevates fasting blood glucose levels; these sequelae persisted for several months. This report describes how episodic hypoxic events elevate a chloride ion exporter, K+-Cl- cotransporter-2 (KCC2), in the plasma membrane of insulin-secreting pancreatic β-cells. We assume that acute diabetic symptoms observed in rat pups with periodic oxygen desaturation could result from a lack of blood insulin levels due to disturbed β-cell function. This acute hypo-insulinemia may result from a disruption in chloride balance in β-cells arising from an imbalanced KCC2-NKCC1 (chloride exporter-importer) density as a consequence of periodic oxygen desaturation. Mechanistically, we postulate that a reduced insulin secretion due to the KCC2-NKCC1 imbalance subsequent to acute oxygen desaturation could result in hyperglycemia in rat pups, paralleling symptoms shown in patients with COVID-19 who experienced acute respiratory distress.
    • Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson's Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

      Santos García, Diego; Naya Ríos, Lucía; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; García Roca, Lucía; Feal Painceiras, Maria; Martínez Miró, Cristina; Canfield, Hector; Jesús, Silvia; Aguilar, Miquel; et al. (MDPI AG, 2021-12-17)
      The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269-4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012-1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale-III (OR = 1.039; 95%CI, 1.023-1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001-1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716).
    • The Patent Ductus Arteriosus in Adults with Special Focus on Role of CT

      Lee, Soo Jeong; Yoo, Seung Min; Son, Min Ji; White, Charles S (MDPI AG, 2021-12-19)
      The primary imaging modality for the diagnosis of patent ductus arteriosus (PDA) is echocardiography. However, CT may be the technique on which an incidental PDA is first recognized because of the increasing number of chest CT scans performed for a variety of causes. Identification of PDA on CT may lead to earlier closure using a PDA occluder device. Immediate identification of incidental PDA is important, but a high rate of missed diagnosis of PDA has been reported due to its small size and anatomic location. In addition, echocardiography may overlook the presence of even a large PDA due to decrease in the amount of shunting through the PDA caused by high pulmonary artery pressures. This review provides the basic CT anatomy and clinical perspective of PDA, and discusses the role of CT in the evaluation of PDA as well as methods to avoid overlooking a small PDA on CT.
    • Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617

      Jin, Jian-Yue; Hu, Chen; Xiao, Ying; Zhang, Hong; Paulus, Rebecca; Ellsworth, Susannah G; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael Chris; Kavadi, Vivek S; et al. (MDPI AG, 2021-12-08)
      Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC-survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1-12.2 Gy) and 6.3 Gy (2.1-11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6-8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.
    • Microtubule-Interfering Drugs: Current and Future Roles in Epithelial Ovarian Cancer Treatment

      Tymon-Rosario, Joan; Adjei, Naomi N; Roque, Dana M; Santin, Alessandro D (MDPI AG, 2021-12-12)
      Taxanes and epothilones are chemotherapeutic agents that ultimately lead to cell death through inhibition of normal microtubular function. This review summarizes the literature demonstrating their current use and potential promise as therapeutic agents in the treatment of epithelial ovarian cancer (EOC), as well as putative mechanisms of resistance. Historically, taxanes have become the standard of care in the front-line and recurrent treatment of epithelial ovarian cancer. In the past few years, epothilones (i.e., ixabepilone) have become of interest as they may retain activity in taxane-treated patients since they harbor several features that may overcome mechanisms of taxane resistance. Clinical data now support the use of ixabepilone in the treatment of platinum-resistant or refractory ovarian cancer. Clinical data strongly support the use of microtubule-interfering drugs alone or in combination in the treatment of epithelial ovarian cancer. Ongoing clinical trials will shed further light into the potential of making these drugs part of current standard practice.
    • Adipose Lipolysis Regulates Cardiac Glucose Uptake and Function in Mice under Cold Stress

      Choi, Youngshim; Shin, Hyunsu; Tang, Ziwei; Yeh, Yute; Ma, Yinyan; Kadegowda, Anil K G; Wang, Huan; Jiang, Long; Arya, Rakesh K; Chen, Ling; et al. (MDPI AG, 2021-12-12)
      The heart primarily uses fatty acids as energy substrates. Adipose lipolysis is a major source of fatty acids, particularly under stress conditions. In this study, we showed that mice with selective inactivation of the lipolytic coactivator comparative gene identification-58 (CGI-58) in adipose tissue (FAT-KO mice), relative to their littermate controls, had lower circulating FA levels in the fed and fasted states due to impaired adipose lipolysis. They preferentially utilized carbohydrates as energy fuels and were more insulin sensitive and glucose tolerant. Under cold stress, FAT-KO versus control mice had >10-fold increases in glucose uptake in the hearts but no increases in other tissues examined. Plasma concentrations of atrial natriuretic peptide and cardiac mRNAs for atrial and brain-type natriuretic peptides, two sensitive markers of cardiac remodeling, were also elevated. After one week of cold exposure, FAT-KO mice showed reduced cardiac expression of several mitochondrial oxidative phosphorylation proteins. After one month of cold exposure, hearts of these animals showed depressed functions, reduced SERCA2 protein, and increased proteins for MHC-β, collagen I proteins, Glut1, Glut4 and phospho-AMPK. Thus, CGI-58-dependent adipose lipolysis critically regulates cardiac metabolism and function, especially during cold adaptation. The adipose-heart axis may be targeted for the management of cardiac dysfunction.
    • Mitigation of CyanoHABs Using Phoslock to Reduce Water Column Phosphorus and Nutrient Release from Sediment

      Li, Ji; Sellner, Kevin; Place, Allen; Cornwell, Jeffrey; Gao, Yonghui (MDPI AG, 2021-12-18)
      Cyanobacterial blooms can be stimulated by excessive phosphorus (P) input, especially when diazotrophs are the dominant species. A series of mesocosm experiments were conducted in a lake dominated by a cyanobacteria bloom to study the effects of Phoslock®, a phosphorus adsorbent. The results showed that the addition of Phoslock® lowered the soluble reactive phosphate (SRP) concentrations in water due to efficient adsorption and mitigated the blooms. Once settled on the sediments, Phoslock® serves as a barrier to reduce P diffusion from sediments into the overlying waters. In short-term (1 day) incubation experiments, Phoslock® diminished or reversed SRP effluxes from bottom sediments. At the same time, the upward movement of the oxic-anoxic interface through the sediment column slightly enhanced NH4+ release and depressed N2 release, suggesting the inhibition of nitrification and denitrification. In a long-term (28 days) experiment, Phoslock® hindered the P release, reduced the cyanobacterial abundance, and alleviated the bloom-driven enhancements in the pH and oxygen. These results suggest that, through suppression of internal nutrient effluxes, Phoslock® can be used as an effective control technology to reduce cyanobacteria blooms common to many freshwater systems.
    • Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case

      Vannella, Kevin M; Oguz, Cihan; Stein, Sydney R; Pittaluga, Stefania; Dikoglu, Esra; Kanwal, Arjun; Ramelli, Sabrina C; Briese, Thomas; Su, Ling; Wu, Xiaolin; et al. (Frontiers Media S.A., 2021-12-09)
      A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.
    • Recombinant Production of Biliverdin IXβ and δ Isomers in the T7 Promoter Compatible Nissle

      Robinson, Elizabeth A; Frankenberg-Dinkel, Nicole; Xue, Fengtian; Wilks, Angela (Frontiers Media S.A., 2021-12-08)
      The ability to obtain purified biliverdin IX (BVIX) isomers other than the commercially available BVIXα is limited due to the low yields obtained by the chemical coupled oxidation of heme. Chemical oxidation requires toxic chemicals, has very poor BVIX yields (<0.05%), and is not conducive to scalable production. Alternative approaches utilizing recombinant E. coli BL21 expressing a cyanobacterial heme oxygenase have been employed for the production BVIXα, but yields are limited by the rate of endogenous heme biosynthesis. Furthermore, the emerging roles of BVIXβ and BVIXδ in biology and their lack of commercial availability has led to a need for an efficient and scalable method with the flexibility to produce all three physiologically relevant BVIX isomers. Herein, we have taken advantage of an optimized non-pathogenic E. coli Nissle (EcN(T7)) strain that encodes an endogenous heme transporter and an integrated T7 polymerase gene. Protein production of the Pseudomonas aeruginosa BVIXβ and BVIXδ selective heme oxygenase (HemO) or its BVIXα producing mutant (HemOα) in the EcN(T7) strain provides a scalable method to obtain all three isomers, that is not limited by the rate of endogenous heme biosynthesis, due to the natural ability of EcN(T7) to transport extracellular heme. Additionally, we have optimized our previous LC-MS/MS protocol for semi-preparative separation and validation of the BVIX isomers. Utilizing this new methodology for scalable production and separation we have increased the yields of the BVIXβ and -δ isomers >300-fold when compared to the chemical oxidation of heme.
    • Evaluating covid-19 vaccine efficacy and safety in the post-authorisation phase.

      Prugger, Christof; Spelsberg, Angela; Keil, Ulrich; Erviti, Juan; Doshi, Peter (BMJ Publishing Group, 2021-12-23)
    • Identification and computational analysis of rare variants of known hearing loss genes present in five deaf members of a pakistani kindred

      Saleem, Irum Badshah; Masoud, Muhammad Shareef; Qasim, Muhammad; Ali, Muhammad; Ahmed, Zubair M. (MDPI AG, 2021-11-30)
      Hearing loss (HL) is the most common neurosensory defect in humans that affects the normal communication. Disease is clinically and genetically heterogeneous, rendering challenges for the molecular diagnosis of affected subjects. This study highlights the phenotypic and genetic complexity of inherited HL in a large consanguineous Pakistan kindred. Audiological evaluation of all affected individuals revealed varying degree of mild to profound sensorineural HL. Whole exome (WES) of four family members followed by Sanger sequencing revealed candidate disease-associated variants in five known deafness genes: GJB2 (c.231G>A; p.(Trp77 *)), SLC26A4 (c.1337A>G; p.(Gln446Arg)), CDH23 (c.2789C>T; p.(Pro930Leu)), KCNQ4 (c.1672G>A; p.(Val558Met)) and MPDZ (c.4124T>C; p.(Val1375Ala)). All identified variants replaced evolutionary conserved residues, were either absent or had low frequencies in the control databases. Our in silico and 3-Dimensional (3D) protein topology analyses support the damaging impact of identified variants on the encoded proteins. However, except for the previously established “pathogenic” and “likely pathogenic” categories for the c.231G>A (p.(Trp77 *)) allele of GJB2 and c.1377A>G (p.(Gln446Arg)) of SLC26A4, respectively, all the remaining identified variants were classified as “uncertain significance” based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines. Our study highlights the complexity of genetic traits in consanguineous families, and the need of combining the functional studies even with the comprehensive profiling of multiple family members to improve the genetic diagnosis in complex inbred families. © 2021 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).
    • Npc1l1 deficiency suppresses ileal fibroblast growth factor 15 expression and increases bile acid pool size in high-fat-diet-fed mice

      Jia, Lin; Ma, Yinyan; Haywood, Jamie; Jiang, Long; Xue, Bingzhong; Shi, Hang; Dawson, Paul A.; Yu, Liqing (MDPI AG, 2021-12-09)
      Niemann–Pick C1-like 1 (NPC1L1) mediates intestinal uptake of dietary and biliary cholesterol and is the target of ezetimibe, a cholesterol absorption inhibitor used to treat hypercholes-terolemia. Genetic deletion of NPC1L1 or ezetimibe treatment protects mice from high-fat diet (HFD)-induced obesity; however, the molecular mechanisms responsible for this therapeutic benefit remain unknown. A major metabolic fate of cholesterol is its conversion to bile acids. We found that NPC1L1 knockout (L1-KO) mice fed an HFD had increased energy expenditure, bile acid pool size, and fecal bile acid excretion rates. The elevated bile acid pool in the HFD-fed L1-KO mice was en-riched with tauro-β-muricholic acid. These changes in the L1-KO mice were associated with reduced ileal mRNA expression of fibroblast growth factor 15 (FGF15) and increased hepatic mRNA expression of cholesterol 7α-hydroxylase (Cyp7A1) and mitochondrial sterol 27-hydroxylase (Cyp27A1). In addition, mRNA expression of the membrane bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) and type 2 iodothyronine deiodinase (Dio2) were elevated in brown adipose tissue of L1-KO mice, which is known to promote energy expenditure. Thus, altered bile acid homeostasis and signaling may play a role in protecting L1-KO mice against HFD-induced obesity. © 2021 by the authors.
    • Heavy ion minibeam therapy: Side effects in normal brain

      Eley, John G.; Haga, Catherine W.; Keller, Asaf; Lazenby, Ellis M.; Raver, Charles; Rusek, Adam; Dilmanian, Farrokh Avraham; Krishnan, Sunil; Waddell, Jaylyn (MDPI AG, 2021-12-09)
      The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium‐7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300‐micron width and 1‐mm center‐to‐center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid‐beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study. © 2021 by the authors.
    • Pathways in skeletal muscle: Protein signaling and insulin sensitivity after exercise training and weight loss interventions in middle-aged and older adults

      Ryan, Alice S.; Li, Guoyan; McMillin, Shawna; Prior, Steven J.; Blumenthal, Jacob B.; Mastella, Laura (MDPI AG, 2021-12-10)
      Aging and obesity contribute to insulin resistance with skeletal muscle being critically important for maintaining whole-body glucose homeostasis. Both exercise and weight loss are lifestyle interventions that can affect glucose metabolism. The purpose of this study was to examine the effects of a six-month trial of aerobic exercise training or weight loss on signaling pathways in skeletal muscle in the basal condition and during hyperinsulinemia during a glucose clamp in middle-aged and older adults. Overweight and obese men and women aged 50–70 years were randomly allocated and completed six months of either weight loss (WL) (n = 18) or 3x/week aerobic exercise training (AEX) (n = 17). WL resulted in 10% weight loss and AEX increased maximal oxygen consumption (VO2 max) (both p &lt; 0.001). Insulin sensitivity (hyperinsulinemic-euglycemic 80 mU·m−2·min−1 clamp) increased in WL and AEX (both p &lt; 0.01). In vivo insulin stimulation increased phosphorylation/total protein ratio (P/T) of protein kinase B (Akt), glycogen synthase kinase 3 beta (GSK-β3), 70 kDa ribosomal protein S6 kinase (p70S6k), insulin receptor substrate 1 (IRS-1), and insulin receptor (IR) expression (all p &lt; 0.05) but not P/T extracellular regulated kinase12 (ERK1/2), c-jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), or insulin-like growth factor 1 receptor (IGF-1R). There were differences between WL and AEX in the change in basal Akt P/T (p = 0.05), GSK-3β P/T ratio (p &lt; 0.01), p70S6k (p &lt; 0.001), ERK1/2 (p = 0.01) P/T ratio but not p38, JNK, IRS-1, and IGF-1R P/T ratios. There was a difference between WL and AEX in the insulin stimulation changes in GSK3 which increased more after WL than AEX (p &lt; 0.05). In the total group, changes in M were associated with changes in basal total GSK-3β and basal total p70Sk as well as insulin stimulation of total p70Sk. Protein signaling in skeletal muscle provides insight as to mechanisms for improvements in insulin sensitivity in aging and obesity. © 2021 by the authors.
    • Is preterm birth associated with intimate partner violence and maternal malnutrition during pregnancy in Ethiopia? A systematic review and meta analysis

      Desta, Melaku; Getaneh, Temesgen; Memiah, Peter; Akalu, Tadesse Yirga; Shiferaw, Wondimeneh Shibabaw; Yimer, Nigus Bililign; Asmare, Biachew; Black, Kirsten I. (Elsevier Inc., 2021-10-06)
      Background: Despite remarkable progress in the reduction of under-five mortality, preterm birth associated mortality and morbidity remains a major public health problem in Sub-saharan Africa. In Ethiopia, study findings on the association of preterm birth with intimate partner violence and maternal malnutrition have been inconsistent. Therefore, this systematic review and meta-analysis estimates the pooled effect of intimate partner violence and maternal malnutrition on preterm birth. Methods: International databases including PubMed, Web of Science, SCOPUS, CINAHL, PsycINFO, Google Scholar, Science Direct, and the Cochrane Library, were systematically searched. All identified observational studies and/or predictors were included. I2 statistics and Egger's test were used to assess the heterogeneity and publication biases of the studies. A random-effects model was computed to estimate the prevalence and its determinants of preterm birth. Results: The random effects meta-analysis showed that a pooled national prevalence of preterm birth was 13% (95% CI: 10.0%, 16.0%). The highest prevalence of preterm birth was 25% (95% CI: 21.0%, 30.0%) in Harar, and the lowest prevalence was 8% in Southern Nations Nationalities People of Representatives. The meta-analysis suggested a decrease in preterm birth of up to 61% among women receiving antenatal care [POR = 0.39 (95% CI: 0.21, 0.72)]. Women who experienced intimate partner violence [POR = 2.52 (95% CI: 1.68, 3.78)], malnutrition during pregnancy [POR = 2.00 (95% CI: 1.16, 3.46)], and previous preterm birth [POR = 3.73 (95% CI: 2.37, 5.88)] had significantly higher odds of preterm birth. Conclusion: One in every eight live births in Ethiopia were preterm. Women who experienced intimate partner violence, malnutrition, and had previous preterm exposure were significantly associated with preterm birth. Thus, improving antenatal care visits and screening women who experience previous preterm birth are key interventions. The Federal Ministry of Health could be instrumental in preventing intimate partner violence and improving the nutritional status of pregnant women through proper and widespread implementation of programs to reduce preterm birth. © 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (
    • Factors associated with refractory pain in emergency patients admitted to emergency general surgery

      Gilliam, William; Barr, Jackson F; Bruns, Brandon; Cave, Brandon; Mitchell, Jordan; Nguyen, Tina; Palmer, Jamie; Rose, Mark; Tanveer, Safura; Yum, Chris; et al. (Second Affiliated Hospital, Zhejiang University School of Medicine, 2021)
      BACKGROUND: Oligoanalgesia in emergency departments (EDs) is multifactorial. A previous study reported that emergency providers did not adequately manage patients with severe pain despite objective findings for surgical pathologies. Our study aims to investigate clinical and laboratory factors, in addition to providers’ interventions, that might have been associated with oligoanalgesia in a group of ED patients with moderate and severe pains due to surgical pathologies. METHODS: We conducted a retrospective study of adult patients who were transferred directly from referring EDs to the emergency general surgery (EGS) service at a quaternary academic center between January 2014 and December 2016. Patients who were intubated, did not have adequate records, or had mild pain were excluded. The primary outcome was refractory pain, which was defined as pain reduction <2 units on the 0-10 pain scale between triage and ED departure. RESULTS: We analyzed 200 patients, and 58 (29%) had refractory pain. Patients with refractory pain had significantly higher disease severity, serum lactate (3.4±2.0 mg/dL vs. 1.4±0.9 mg/dL, P=0.001), and less frequent pain medication administration (median [interquartile range], 3 [3-5] vs. 4 [3-7], P=0.001), when compared to patients with no refractory pain. Multivariable logistic regression showed that the number of pain medication administration (odds ratio [OR] 0.80, 95% confidence interval [95% CI] 0.68-0.98) and ED serum lactate levels (OR 3.80, 95% CI 2.10-6.80) were significantly associated with the likelihood of refractory pain. CONCLUSIONS: In ED patients transferring to EGS service, elevated serum lactate levels were associated with a higher likelihood of refractory pain. Future studies investigating pain management in patients with elevated serum lactate are needed.
    • Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

      Tin, Adrienne; Schlosser, Pascal; Matias-Garcia, Pamela R; Thio, Chris H L; Joehanes, Roby; Liu, Hongbo; Yu, Zhi; Weihs, Antoine; Hoppmann, Anselm; Grundner-Culemann, Franziska; et al. (Springer Nature, 2021-12-09)
      Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
    • The Effect of an Automated Mobile Patient Engagement Application on Emergency Department Revisits: Prospective Observational Study

      Chatterjee, Pothik; Beck, Adam M; Brager, Jenna Ashley Levenson; Durand, Daniel J; D'Adamo, Christopher R (JMIR Publications, 2021-12-13)
      BACKGROUND: Revisits within 30 days to an emergency department (ED), observation care unit, or inpatient setting following patient discharge continue to be a challenge, especially in urban settings. In addition to the consequences for the patient, these revisits have a negative impact on a health system's finances in a value-based care or global budget environment. LifeBridge Health, a community health system in Maryland, United States, implemented an automated mobile patient engagement application as part of our enterprise-wide digital health strategy to improve patient engagement and reduce revisits to the ED. OBJECTIVE: The aim of this paper was to evaluate the effectiveness of a customized automated digital patient engagement application (GetWell Loop) to reduce 30-day revisits after home discharge from an ED. METHODS: The LifeBridge Health Innovation Department and ED staff from 2 participating health system hospitals collaborated with GetWellNetwork to customize their patient engagement application with automated check-in questions and other on-demand resources (eg, streaming content explaining aspects of self-care during COVID-19). An application link was emailed to adult patients discharged home from the ED. A study of ED visits for patients treated for general medicine and cardiology conditions between August 1, 2018, and July 31, 2019, was conducted using CRISP (Chesapeake Regional Information System for our Patients), Maryland's state-designated health information exchange. We also used data within GetWell Loop (GetWellNetwork) to track patient activation and engagement. The primary outcome was the number of ED patients who experienced a 30-day revisit and who did or did not activate their GetWell Loop account. Secondary outcomes included the overall activation rate and the rate of engagement as measured by the number of logins, alerts, and comments generated by patients through the application. Bivariate analysis comparing outcomes among patients who activated the GetWell Loop application to patients who did not was conducted using the Fisher exact test. Multivariate logistic regression modeling with elastic net regularization was also performed to account for potential confounders and potential collinearity of covariates. RESULTS: During this 1-year study, 1062 (27.4%) of 3866 of all emergency patients treated for general medicine or cardiology conditions, who received an invite to use the digital application, activated their account. The patients discharged from the ED, who were treated for general medicine conditions (n=2087) and who activated their GetWell Loop account, experienced a 30-day revisit rate of 17.3% (n=101) compared with 24.6% (n=369) for those who did not activate their account (P<.001). Of the patients treated for cardiology conditions (n=1779), 12.8% (n=61) of those who activated their GetWell account experienced a 30-day revisit compared with 17.7% (n=231) of those who did not activate their account (P=.01). The significance of these findings persisted after adjustment for confounding variables including age, race, sex, and payor in logistic regression modeling (adjusted odds ratio 0.75, 95% CI 0.62-0.92; P=.006). CONCLUSIONS: Our results suggest that a significant percentage of patients are willing to utilize a digital application following ED discharge to better engage in their own care, and that usage of such digital applications may significantly reduce 30-day revisit rates. LifeBridge Health's experience demonstrates that health care systems can leverage automated mobile apps to improve patient engagement and successfully impact clinical outcomes at scale.