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  • Ovid Technologies (Wolters Kluwer Health)  (15)
  • 1
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    Online Resource
    Hypobaria during long-range flight resulted in significantly increased histopathological evidence of lung and brain damage in a swine model
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Journal of Trauma and Acute Care Surgery Vol. 86, No. 1 ( 2019-1), p. 116-122
    Details
    In: Journal of Trauma and Acute Care Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 86, No. 1 ( 2019-1), p. 116-122
    Abstract: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine. METHODS Anesthetized Yorkshire swine underwent a simulated 4 h “transport” to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis. RESULTS All parameters were similar prior to and after “transport” with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals. CONCLUSION Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.
    Type of Medium: Online Resource
    ISSN: 2163-0763 , 2163-0755
    URL: Article
    DOI: 10.1097/TA.0000000000002014
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2651313-4
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  • 2
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    Abstract 548: Evolutionarily Conserved Functions for Valosin Containing Protein (VCP) in Cardiac and Skeletal Muscle Reveal Mechanistic Insights into Multisystem Proteinopathy
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation Research Vol. 123, No. Suppl_1 ( 2018-08-03)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 123, No. Suppl_1 ( 2018-08-03)
    Abstract: Valosin Containing Protein (VCP)/p97 is a AAA-ATPase with functions in vast cellular protein quality control processes, including targeting of misfolded or aggregated proteins for degradation by the ubiquitin proteasome system and autophagy. Mutations in VCP cause a multisystem degenerative proteinopathy disorder that includes pathologies of the nervous system, skeletal muscle, bone, and heart. However, the molecular function of VCP in myocytes is unknown. We generated cardiomyocyte-specific transgenic mice overexpressing wildtype VCP or a VCP K524A mutant with deficient ATPase activity. Mice overexpressing wildtype VCP exhibit normal cardiac structure and function while mutant VCP overexpressing mice develop cardiomyopathy and have elevated levels of ubiquitinated proteins in the heart. Additionally, we generated transgenic flies overexpressing wildtype VCP or VCP K524A in muscle. Flies overexpressing the VCP ATPase-deficient mutant have reduced flight ability at two days of age and are unable to fly at seven days of age, suggesting conserved indispensable homeostatic functions for VCP in heart and skeletal muscle. Moreover, mouse hearts and Drosophila indirect flight muscle overexpressing the ATPase-deficient VCP mutant exhibit profound ultrastructural abnormalities consistent with dysregulation of proteostasis. Extensive proteomics in Drosophila and in mouse heart identified conserved interactions of VCP with protein complexes that suggest unique functions for VCP in regulating novel quality control pathways in muscle. These data and novel regulatory relationships will be presented, which implicate important and evolutionarily conserved functions for VCP and suggest molecular mechanisms that underlie the molecular etiology of multisystem proteinopathy disorders.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.123.suppl_1.548
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1467838-X
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  • 3
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    Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 8 ( 2021-08), p. 2502-2509
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 8 ( 2021-08), p. 2502-2509
    Abstract: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%] ; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%] ; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%] ; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%] ; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.033070
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 4
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    Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Abstract: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92] ; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.056290
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 5
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    Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation: Heart Failure Vol. 12, No. 11 ( 2019-11)
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 11 ( 2019-11)
    Abstract: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84–0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72–0.97 for Latinx). Female sex and age 〉 75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.119.006214
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2428100-1
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  • 6
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    Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 96, No. 10 ( 2021-03-9), p. e1470-e1481
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 10 ( 2021-03-9), p. e1470-e1481
    Abstract: To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF β-amyloid (Aβ) 42 /Aβ 40 and phosopho-tau 181 (p-tau 181 ) in cognitively unimpaired older adults (CU). Methods CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ 42 , Aβ 40 , and p-tau 181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word–picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied “target” objects, novel “foil” objects, and perceptually similar “lure” objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. Results Age and lower Aβ 42 /Aβ 40 were independently associated with elevated p-tau 181 . Age, Aβ 42 /Aβ 40 , and p-tau 181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target–lure similarity). P-tau mediated the effect of Aβ 42 /Aβ 40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aβ 42 was not significantly associated with p-tau 181 or memory. Conclusions Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000011477
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 7
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    Effect of Chlorhexidine Bathing Every Other Day on Prevention of Hospital-Acquired Infections in the Surgical ICU: A Single-Center, Randomized Controlled Trial*
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Critical Care Medicine Vol. 44, No. 10 ( 2016-10), p. 1822-1832
    Details
    In: Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 10 ( 2016-10), p. 1822-1832
    Abstract: To test the hypothesis that compared with daily soap and water bathing, 2% chlorhexidine gluconate bathing every other day for up to 28 days decreases the risk of hospital-acquired catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection in surgical ICU patients. Design: This was a single-center, pragmatic, randomized trial. Patients and clinicians were aware of treatment-group assignment; investigators who determined outcomes were blinded. Setting: Twenty-four–bed surgical ICU at a quaternary academic medical center. Patients: Adults admitted to the surgical ICU from July 2012 to May 2013 with an anticipated surgical ICU stay for 48 hours or more were included. Interventions: Patients were randomized to bathing with 2% chlorhexidine every other day alternating with soap and water every other day (treatment arm) or to bathing with soap and water daily (control arm). Measurements and Main Results: The primary endpoint was a composite outcome of catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection. Of 350 patients randomized, 24 were excluded due to prior enrollment in this trial and one withdrew consent. Therefore, 325 were analyzed (164 soap and water versus 161 chlorhexidine). Patients acquired 53 infections. Compared with soap and water bathing, chlorhexidine bathing every other day decreased the risk of acquiring infections (hazard ratio = 0.555; 95% CI, 0.309–0.997; p = 0.049). For patients bathed with soap and water versus chlorhexidine, counts of incident hospital-acquired infections were 14 versus 7 for catheter-associated urinary tract infection, 13 versus 8 for ventilator-associated pneumonia, 6 versus 3 for incisional surgical site infections, and 2 versus 0 for primary bloodstream infection; the effect was consistent across all infections. The absolute risk reduction for acquiring a hospital-acquired infection was 9.0% (95% CI, 1.5–16.4%; p = 0.019). Incidences of adverse skin occurrences were similar (18.9% soap and water vs 18.6% chlorhexidine; p = 0.95). Conclusions: Compared with soap and water, chlorhexidine bathing every other day decreased the risk of acquiring infections by 44.5% in surgical ICU patients.
    Type of Medium: Online Resource
    ISSN: 0090-3493
    URL: Article
    DOI: 10.1097/CCM.0000000000001820
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2034247-0
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  • 8
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    Bacterial Colonization of the Hospitalized Newborn: Competition Between Staphylococcus aureus and Staphylococcus epidermidis
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Pediatric Infectious Disease Journal Vol. 38, No. 7 ( 2019-07), p. 682-686
    Details
    In: Pediatric Infectious Disease Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 7 ( 2019-07), p. 682-686
    Abstract: In adults, Staphylococcus epidermidis and Staphylococcus aureus compete for colonization of the nasal mucosa and S. epidermidis strains that produce the Esp serine protease eradicate S. aureus nasal colonization. Whether similar phenomena are seen in newborn infants is unknown. Methods: Nasal swabs were obtained on admission and discharge from newborn infants (n = 90 and 83, respectively) in the neonatal intensive care unit at UC Davis Children’s Hospital. Swabs were cultured for S. aureus and S. epidermidis . S. epidermidis isolates were tested for Esp expression, overall secreted protease activity and biofilm inhibition. Results: No infant had S. aureus on admission. S. epidermidis colonization was rare on admission in inborn infants (2.5%), but common in infants transferred from referring hospitals (50%). At discharge, most infants (96%) were colonized by staphylococci. S. aureus colonization was less common in infants with S. epidermidis colonization (9%) and more common in infants without S. epidermidis (77%) (relative risk of S. aureus colonization in infants colonized with S. epidermidis 0.18, 95% confidence interval: 0.089–0.34, P 〈 0.0001). Compared with S. epidermidis strains from infants without S. aureus , S. epidermidis from infants co-colonized with S. aureus had lower total proteolytic enzyme activity and decreased biofilm inhibition capacity, but did not have lower frequency of Esp positivity. Conclusions: In hospitalized neonates, S. epidermidis colonization has a protective effect against S. aureus colonization. Secretion of proteases by S. epidermidis is a possible mechanism of inhibition of S. aureus colonization; however, in this cohort of neonates, the source of major protease activity is likely other than Esp.
    Type of Medium: Online Resource
    ISSN: 0891-3668
    URL: Article
    DOI: 10.1097/INF.0000000000002285
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2020216-7
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  • 9
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    AKI in Children Hospitalized with Nephrotic Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Clinical Journal of the American Society of Nephrology Vol. 10, No. 12 ( 2015-12), p. 2110-2118
    Details
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 12 ( 2015-12), p. 2110-2118
    Type of Medium: Online Resource
    ISSN: 1555-9041
    URL: Article
    DOI: 10.2215/CJN.06620615
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2216582-4
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  • 10
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    Psychometric Evaluation of the Kansas City Cardiomyopathy Questionnaire in Men and Women With Heart Failure
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation: Heart Failure Vol. 14, No. 9 ( 2021-09)
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. 9 ( 2021-09)
    Abstract: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown. Methods: Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined. Results: The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: −0.40 in men versus −0.49 in women) and acute (−0.37 in men versus −0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability. Conclusions: The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.120.008284
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2428100-1
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