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  1. Article ; Online: Care-engaged individuals with polysubstance use in Northeastern US are undertreated for methamphetamine use disorder

    Mimi Yen Li / George A. Alba / Julian Mitton / Benjamin Bearnot

    Addiction Science & Clinical Practice, Vol 16, Iss 1, Pp 1-

    a retrospective cohort study

    2021  Volume 9

    Abstract: Abstract Background Stimulant use has increased across the US, with concomitant opioid and methamphetamine use doubling between 2011 and 2017. Shifting patterns of polysubstance use have led to rising psychostimulant-involved deaths. While it is known ... ...

    Abstract Abstract Background Stimulant use has increased across the US, with concomitant opioid and methamphetamine use doubling between 2011 and 2017. Shifting patterns of polysubstance use have led to rising psychostimulant-involved deaths. While it is known that individuals who use methamphetamine require greater access to treatment, there is still little known about methamphetamine use and treatment among individuals who are already engaged in outpatient substance use treatment. Objectives To characterize care-engaged individuals who use methamphetamine to guide harm reduction and treatment strategies. Methods Retrospective cohort study of individuals at a large academic medical center in Massachusetts with ≥ 2 positive methamphetamine oral fluid toxicology tests between August 2019 and January 2020. We performed descriptive analysis of sociodemographic, medical, and drug use characteristics and a comparative analysis of injection methamphetamine use versus other routes of use. Results Included were 71 individuals [56 male (80%), 66 non-Hispanic white (94%), median age 36 (IQR 30–42)]. Nearly all had opioid (94%) and stimulant use disorder (92%). Most had (93%) or were (83%) being treated with medications for opioid use disorder, but few received pharmacologic treatment for methamphetamine use disorder (24%). None received contingency management treatment. People who inject methamphetamine (68%) were more likely to have a history of overdose (91% vs. 70%; p = 0.02), have HCV (94% vs. 52%; p < 0.01), use fentanyl (93% vs. 65%; p = 0.02), and engage in sex work (19% vs. 0%; p = 0.03) compared to those who used via other routes. Both groups had prevalent homelessness (88% vs. 73%; p = 0.15), incarceration (81% vs. 64%; p = 0.11), depression (94% vs. 87%; p = 0.34), and bacteremia (27% vs. 22%; p = 0.63). Conclusions Individuals in our study had high prevalence of polysubstance use, particularly concomitant methamphetamine and opioid use. Individuals who were well connected to substance use treatment for their opioid ...
    Keywords Methamphetamine ; Opioid crisis ; Harm reduction ; Stimulants ; Drug overdose ; Medicine (General) ; R5-920 ; Social pathology. Social and public welfare. Criminology ; HV1-9960
    Subject code 360
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection

    George A. Alba / Andriy O. Samokhin / Rui‐Sheng Wang / Bradley M. Wertheim / Kathleen J. Haley / Robert F. Padera / Sara O. Vargas / Ivan O. Rosas / Lida P. Hariri / Angela Shih / Boyd Taylor Thompson / Richard N. Mitchell / Bradley A. Maron

    Pulmonary Circulation, Vol 12, Iss 2, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection is incompletely characterized. In human pulmonary artery endothelial ... ...

    Abstract Abstract The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia increases neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and induces expression of a prothrombotic NEDD9 peptide (N9P) on the extracellular plasma membrane surface. We hypothesized that the SARS‐CoV‐2–ARDS pathophenotype involves increased pulmonary endothelial N9P. Paraffin‐embedded autopsy lung specimens were acquired from patients with SARS‐CoV‐2–ARDS (n = 13), ARDS from other causes (n = 10), and organ donor controls (n = 5). Immunofluorescence characterized the expression of N9P, fibrin, and transcription factor 12 (TCF12), a putative binding target of SARS‐CoV‐2 and known transcriptional regulator of NEDD9. We performed RNA‐sequencing on normal HPAECs treated with normoxia or hypoxia (0.2% O2) for 24 h. Immunoprecipitation‐liquid chromatography‐mass spectrometry (IP‐LC‐MS) profiled protein–protein interactions involving N9P relevant to thrombus stabilization. Hypoxia increased TCF12 messenger RNA significantly compared to normoxia in HPAECs in vitro (+1.19‐fold, p = 0.001; false discovery rate = 0.005), and pulmonary endothelial TCF12 expression was increased threefold in SARS‐CoV‐2–ARDS versus donor control lungs (p < 0.001). Compared to donor controls, pulmonary endothelial N9P‐fibrin colocalization was increased in situ in non‐SARS‐CoV‐2–ARDS and SARS‐CoV‐2–ARDS decedents (3.7 ± 1.2 vs. 10.3 ± 3.2 and 21.8 ± 4.0 arb. units, p < 0.001). However, total pulmonary endothelial N9P was increased significantly only in SARS‐CoV‐2–ARDS versus donor controls (15 ± 4.2 vs. 6.3 ± 0.9 arb. units, p < 0.001). In HPAEC plasma membrane isolates, IP‐LC‐MS identified a novel protein–protein interaction between NEDD9 and the β3‐subunit of the αvβ3‐integrin, which regulates fibrin anchoring to endothelial cells. In ...
    Keywords acute respiratory distress syndrome ; endothelium ; pulmonary biology ; SARS‐CoV‐2 ; thrombosis ; Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Diseases of the respiratory system ; RC705-779
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Code status orders in patients admitted to the intensive care unit with COVID-19

    Emily E. Moin / Daniel Okin / Sirus J. Jesudasen / Nupur A. Dandawate / Alexander Gavralidis / Leslie L. Chang / Alison S. Witkin / Kathryn A. Hibbert / Aran Kadar / Patrick L. Gordan / Lisa M. Bebell / Peggy S. Lai / George A. Alba

    Resuscitation Plus, Vol 10, Iss , Pp 100219- (2022)

    A retrospective cohort study

    2022  

    Abstract: Purpose: Code status orders impact clinical outcomes as well as patients’ and surrogates’ experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a ... ...

    Abstract Purpose: Code status orders impact clinical outcomes as well as patients’ and surrogates’ experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission. Results: Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05–1.15, p < 0.001 and adjusted OR 2.68, CI 1.23–5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10–0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change. Conclusions: The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.
    Keywords Code status ; Critical care ; COVID-19 ; Specialties of internal medicine ; RC581-951
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Exercise performance in patients with post-acute sequelae of SARS-CoV-2 infection compared to patients with unexplained dyspnea

    George A. Alba / David R. Ziehr / Jennifer N. Rouvina / Lida P. Hariri / Rachel S. Knipe / Benjamin D. Medoff / Kathryn A. Hibbert / Alyssa Kowal / Casey Hoenstine / Leo C. Ginns / Gregory D. Lewis / C. Corey Hardin

    EClinicalMedicine, Vol 39, Iss , Pp 101066- (2021)

    2021  

    Abstract: Background: Dyspnea and exercise intolerance are commonly reported post-acute sequelae of SARS-CoV-2 infection (PASC), but routine diagnostic testing is often normal. Cardiopulmonary exercise testing (CPET) offers comprehensive assessment of dyspnea to ... ...

    Abstract Background: Dyspnea and exercise intolerance are commonly reported post-acute sequelae of SARS-CoV-2 infection (PASC), but routine diagnostic testing is often normal. Cardiopulmonary exercise testing (CPET) offers comprehensive assessment of dyspnea to characterize pulmonary PASC. Methods: We performed a retrospective cohort study of CPET performed on patients reporting dyspnea and/or exercise intolerance following confirmed Covid-19 between August 1, 2020 and March 1, 2021, and compared them to age- and sex-matched patients with unexplained dyspnea referred for CPET at the same center in the pre-Covid-19 era. Findings: Compared to matched unexplained dyspnea comparators, PASC patients shared similar medical comorbidities and subjective dyspnea at referral (mMRC score 1.6 ± 0.9 vs. 1.4 ± 0.9, P = 0.5). Fifteen (83.3%) PASC patients underwent high resolution computed tomography of the chest, of which half (46.7%) were normal, and 17 (94.4%) patients had pulmonary function testing, of which the majority (76.5%) were normal. All patients underwent CPET, and 12 (67%) had normal findings. Compared to matched comparators, PASC patients had similar peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, and ventilatory efficiency measured by the minute ventilation to carbon dioxide production (VE/VCO2) slope. Interpretation: Despite prominent dyspnea, physiological abnormalities on CPET were mild across a range of initial Covid-19 severity and similar to matched comparators referred for dyspnea without antecedent SARS-CoV-2. Funding: The project was supported by the NHLBI (R01HL131029, R01HL151841, U10HL110337, T32HL116275) and a KL2 award (5KL2TR002542–02) from Harvard Catalyst.
    Keywords Post-acute sequelae of SARS-CoV-2 infection ; Cardiopulmonary exercise test ; COVID-19 ; SARS-CoV-2 ; Dyspnea ; Exercise intolerance ; Medicine (General) ; R5-920
    Subject code 796
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Isolating pulmonary microvascular endothelial cells ex vivo

    Bradley M Wertheim / Yi-Dong Lin / Ying-Yi Zhang / Andriy O Samokhin / George A Alba / Elena Arons / Paul B Yu / Bradley A Maron

    PLoS ONE, Vol 14, Iss 2, p e

    Implications for pulmonary arterial hypertension, and a caution on the use of commercial biomaterials.

    2019  Volume 0211909

    Abstract: Transcriptomic analysis of pulmonary microvascular endothelial cells from experimental models offers insight into pulmonary arterial hypertension (PAH) pathobiology. However, culturing may alter the molecular profile of endothelial cells prior to ... ...

    Abstract Transcriptomic analysis of pulmonary microvascular endothelial cells from experimental models offers insight into pulmonary arterial hypertension (PAH) pathobiology. However, culturing may alter the molecular profile of endothelial cells prior to analysis, limiting the translational relevance of results. Here we present a novel and validated method for isolating RNA from pulmonary microvascular endothelial cells (PMVECs) ex vivo that does not require cell culturing. Initially, presumed rat PMVECs were isolated from rat peripheral lung tissue using tissue dissociation and enzymatic digestion, and cells were cultured until confluence to assess endothelial marker expression. Anti-CD31, anti-von Willebrand Factor, and anti-α-smooth muscle actin immunocytochemistry/immunofluorescence signal was detected in presumed rat PMVECs, but also in non-endothelial cell type controls. By contrast, flow cytometry using an anti-CD31 antibody and isolectin 1-B4 (from Griffonia simplicifolia) was highly specific for rat PMVECs. We next developed a strategy in which the addition of an immunomagnetic selection step for CD31+ cells permitted culture-free isolation of rat PMVECs ex vivo for RNA isolation and transcriptomic analysis using fluorescence-activated cell sorting. Heterogeneity in the validity and reproducibility of results using commercial antibodies against endothelial surface markers corresponded to a substantial burden on laboratory time, labor, and scientific budget. We demonstrate a novel protocol for the culture-free isolation and transcriptomic analysis of rat PMVECs with translational relevance to PAH. In doing so, we highlight wide variability in the quality of commonly used biological reagents, which emphasizes the importance of investigator-initiated validation of commercial biomaterials.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Updated guidance on the management of COVID-19

    Chunxue Bai / Sanjay H. Chotirmall / Jordi Rello / George A. Alba / Leo C. Ginns / Jerry A. Krishnan / Robert Rogers / Elisabeth Bendstrup / Pierre-Regis Burgel / James D. Chalmers / Abigail Chua / Kristina A. Crothers / Abhijit Duggal / Yeon Wook Kim / John G. Laffey / Carlos M. Luna / Michael S. Niederman / Ganesh Raghu / Julio A. Ramirez /
    Jordi Riera / Oriol Roca / Maximiliano Tamae-Kakazu / Antoni Torres / Richard R. Watkins / Miriam Barrecheguren / Mirko Belliato / Hassan A. Chami / Rongchang Chen / Gustavo A. Cortes-Puentes / Charles Delacruz / Margaret M. Hayes / Leo M.A. Heunks / Steven R. Holets / Catherine L. Hough / Sugeet Jagpal / Kyeongman Jeon / Takeshi Johkoh / May M. Lee / Janice Liebler / Gerry N. McElvaney / Ari Moskowitz / Richard A. Oeckler / Iñigo Ojanguren / Anthony O'Regan / Mathias W. Pletz / Chin Kook Rhee / Marcus J. Schultz / Enrico Storti / Charlie Strange / Carey C. Thomson / Francesca J. Torriani / Xun Wang / Wim Wuyts / Tao Xu / Dawei Yang / Ziqiang Zhang / Kevin C. Wilson

    European Respiratory Review, Vol 29, Iss

    from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020)

    2020  Volume 157

    Abstract: Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task ... ...

    Abstract Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.
    Keywords Diseases of the respiratory system ; RC705-779 ; covid19
    Subject code 150
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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