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Non-alcoholic fatty liver disease and cognitive function in middle-aged adults: the CARDIA study.
Gerber Y, VanWagner LB, Yaffe K, Terry JG, Rana JS, Reis JP, Sidney S
(2021) BMC Gastroenterol 21: 96
MeSH Terms: Cognition, Cross-Sectional Studies, Female, Humans, Male, Memory, Middle Aged, Non-alcoholic Fatty Liver Disease, Risk Factors, Young Adult
Show Abstract · Added April 20, 2021
BACKGROUND - Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.
METHODS - Coronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010-2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.
RESULTS - Participants' mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05).
CONCLUSION - Among middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.
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10 MeSH Terms
Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.
Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, Jackson JC, Hoskins AS, Pun BT, Orun OM, Raman R, Stollings JL, Kiehl AL, Duprey MS, Bui LN, O'Neal HR, Snyder A, Gropper MA, Guntupalli KK, Stashenko GJ, Patel MB, Brummel NE, Girard TD, Dittus RS, Bernard GR, Ely EW, Pandharipande PP, MENDS2 Study Investigators
(2021) N Engl J Med 384: 1424-1436
MeSH Terms: Adult, Cognition, Conscious Sedation, Critical Illness, Dexmedetomidine, Double-Blind Method, Humans, Hypnotics and Sedatives, Kaplan-Meier Estimate, Propofol, Respiration, Artificial, Sepsis
Show Abstract · Added May 25, 2021
BACKGROUND - Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.
METHODS - In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.
RESULTS - Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.
CONCLUSIONS - Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).
Copyright © 2021 Massachusetts Medical Society.
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Interim analysis of an open-label randomized controlled trial evaluating nasal irrigations in non-hospitalized patients with coronavirus disease 2019.
Kimura KS, Freeman MH, Wessinger BC, Gupta V, Sheng Q, Huang LC, Von Wahlde K, Das SR, Chowdhury NI, Turner JH
(2020) Int Forum Allergy Rhinol 10: 1325-1328
MeSH Terms: Adult, COVID-19, Female, Humans, Male, Middle Aged, Nasal Lavage, SARS-CoV-2, Saline Solution, Hypertonic, Surface-Active Agents, Treatment Outcome
Added September 23, 2020
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Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study.
Lentz RJ, Colt H, Chen H, Cordovilla R, Popevic S, Tahura S, Candoli P, Tomassetti S, Meachery GJ, Cohen BP, Harris BD, Talbot TR, Maldonado F
(2021) Infect Control Hosp Epidemiol 42: 381-387
MeSH Terms: Adult, Aged, COVID-19, Case-Control Studies, Female, Global Health, Humans, Infectious Disease Transmission, Patient-to-Professional, Logistic Models, Male, Middle Aged, Occupational Exposure, Personal Protective Equipment, Respiratory Protective Devices, Young Adult
Show Abstract · Added May 17, 2021
OBJECTIVE - To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
DESIGN - Case-control study.
SETTING - We collected data from international participants via an online survey.
PARTICIPANTS - In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
METHODS - Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
RESULTS - HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7).
CONCLUSIONS - COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
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Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity.
Miller JM, Meki MH, Ou Q, George SA, Gams A, Abouleisa RRE, Tang XL, Ahern BM, Giridharan GA, El-Baz A, Hill BG, Satin J, Conklin DJ, Moslehi J, Bolli R, Ribeiro AJS, Efimov IR, Mohamed TMA
(2020) Toxicol Appl Pharmacol 406: 115213
MeSH Terms: Adult, Aged, Animals, Antineoplastic Agents, Apoptosis, Cardiotoxicity, Cardiotoxins, Doxorubicin, Female, Heart, Humans, Induced Pluripotent Stem Cells, Male, Middle Aged, Models, Biological, Swine, Tissue Culture Techniques, Trastuzumab
Show Abstract · Added September 29, 2020
The limited availability of human heart tissue and its complex cell composition are major limiting factors for the reliable testing of drug efficacy and toxicity. Recently, we developed functional human and pig heart slice biomimetic culture systems that preserve the viability and functionality of 300 μm heart slices for up to 6 days. Here, we tested the reliability of this culture system for testing the cardiotoxicity of anti-cancer drugs. We tested three anti-cancer drugs (doxorubicin, trastuzumab, and sunitinib) with known different mechanisms of cardiotoxicity at three concentrations and assessed the effect of these drugs on heart slice viability, structure, function and gene expression. Slices incubated with any of these drugs for 48 h showed diminished in viability as well as loss of cardiomyocyte structure and function. Mechanistically, RNA sequencing of doxorubicin-treated tissues demonstrated a significant downregulation of cardiac genes and upregulation of oxidative stress responses. Trastuzumab treatment downregulated cardiac muscle contraction-related genes consistent with its clinically known effect on cardiomyocytes. Interestingly, sunitinib treatment resulted in significant downregulation of angiogenesis-related genes, in line with its mechanism of action. Similar to hiPS-derived-cardiomyocytes, heart slices recapitulated the expected toxicity of doxorubicin and trastuzumab, however, slices were superior in detecting sunitinib cardiotoxicity and mechanism in the clinically relevant concentration range of 0.1-1 μM. These results indicate that heart slice culture models have the potential to become a reliable platform for testing and elucidating mechanisms of drug cardiotoxicity.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Optimizing Genetic Analyses of Serum Lipids in Longitudinal Data.
Chen HH, Petty LE, Gamazon ER, Wells QS, Below JE
(2020) Circ Res 127: 1337-1339
MeSH Terms: Adolescent, Adult, Aged, Biological Variation, Population, Cholesterol, HDL, Data Interpretation, Statistical, Electronic Health Records, Female, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, Models, Genetic
Added September 9, 2020
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Mortality and Pre-Hospitalization use of Renin-Angiotensin System Inhibitors in Hypertensive COVID-19 Patients.
Chen C, Wang F, Chen P, Jiang J, Cui G, Zhou N, Moroni F, Moslehi JJ, Ammirati E, Wang DW
(2020) J Am Heart Assoc 9: e017736
MeSH Terms: Adult, Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, COVID-19, China, Coronavirus Infections, Female, Hospital Mortality, Humans, Hypertension, Male, Middle Aged, Pandemics, Patient Admission, Pneumonia, Viral, Prognosis, Protective Factors, Renin-Angiotensin System, Retrospective Studies, Risk Assessment, Risk Factors
Show Abstract · Added September 29, 2020
Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15-0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non-RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non-RAS inhibitors group. The RAS inhibitors group compared with non-RAS inhibitors group had lower levels of C-reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin-6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta-analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre-hospitalization use of RAS inhibitors on mortality in hypertensive COVID-19 patients; which might be associated with reduced inflammatory response.
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Association of uterine fibroids with birthweight and gestational age.
Zhao SK, Wu P, Jones SH, Torstenson ES, Hartmann KE, Velez Edwards DR
(2020) Ann Epidemiol 50: 35-40.e2
MeSH Terms: Adult, Birth Weight, Cohort Studies, Female, Fetal Development, Gestational Age, Humans, Leiomyoma, Pregnancy, Prospective Studies, Ultrasonography, Uterine Neoplasms
Show Abstract · Added August 5, 2020
PURPOSE - To determine if fibroids or their characteristics are associated with birthweight and/or gestational age, and to assess the impact of race or ethnicity.
METHODS - Right from the Start (2000-2012) is a prospective cohort that enrolled women from the southern US in early pregnancy. Transvaginal ultrasounds were used to measure fibroid characteristics and confirm gestational age. Date of birth and birthweight were obtained from vital or medical records. We assessed whether fibroid presence, number, type, and volume were associated with birthweight and/or gestational age using multivariate analysis of covariance, accounting for a priori confounders.
RESULTS - Among 3926 women, 416 had one or more fibroids. Mean infant birthweight and gestational age were similar among women with and without fibroids. When adjusting for race or ethnicity, all associations were attenuated. Overall, women with and without fibroids had infants of similar birthweight (-20 grams, 95% confidence interval [CI] -77, 36) and gestational age (0.4 days, 95% CI -0.9, 1.8). Women with three or more fibroids were more likely to have lighter infants (-201 grams, 95% CI -345, -58).
CONCLUSIONS - Race or ethnicity substantially confounds the associations. The clinical belief that uterine fibroids impair fetal growth is supported only by a significant decrease in birthweight for women with multiple fibroids.
Copyright © 2020 Elsevier Inc. All rights reserved.
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12 MeSH Terms
Association of smoking with abdominal adipose deposition and muscle composition in Coronary Artery Risk Development in Young Adults (CARDIA) participants at mid-life: A population-based cohort study.
Terry JG, Hartley KG, Steffen LM, Nair S, Alman AC, Wellons MF, Jacobs DR, Tindle HA, Carr JJ
(2020) PLoS Med 17: e1003223
MeSH Terms: Abdominal Fat, Adiposity, Adult, Blood Pressure, Body Mass Index, Cohort Studies, Female, Humans, Intra-Abdominal Fat, Life Style, Male, Middle Aged, Muscle, Skeletal, Obesity, Abdominal, Risk Factors, Smoking, Tomography, X-Ray Computed
Show Abstract · Added July 28, 2020
BACKGROUND - Smokers have lower risk of obesity, which some consider a "beneficial" side effect of smoking. However, some studies suggest that smoking is simultaneously associated with higher central adiposity and, more specifically, ectopic adipose deposition. Little is known about the association of smoking with intermuscular adipose tissue (IMAT), an ectopic adipose depot associated with cardiovascular disease (CVD) risk and a key determinant of muscle quality and function. We tested the hypothesis that smokers have higher abdominal IMAT and lower lean muscle quality than never smokers.
METHODS AND FINDINGS - We measured abdominal muscle total, lean, and adipose volumes (in cubic centimeters) and attenuation (in Hounsfield units [HU]) along with subcutaneous (SAT) and visceral adipose tissue (VAT) volumes using computed tomography (CT) in 3,020 middle-aged Coronary Artery Risk Development in Young Adults (CARDIA) participants (age 42-58, 56.3% women, 52.6% white race) at the year 25 (Y25) visit. The longitudinal CARDIA study was initiated in 1985 with the recruitment of young adult participants (aged 18-30 years) equally balanced by female and male sex and black and white race at 4 field centers located in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Multivariable linear models included potential confounders such as physical activity and dietary habits along with traditional CVD risk factors. Current smokers had lower BMI than never smokers. Nevertheless, in the fully adjusted multivariable model with potential confounders, including BMI and CVD risk factors, adjusted mean (95% CI) IMAT volume was 2.66 (2.55-2.76) cm3 in current smokers (n = 524), 2.36 (2.29-2.43) cm3 in former smokers (n = 944), and 2.23 (2.18-2.29) cm3 in never smokers (n = 1,552) (p = 0.007 for comparison of former versus never smoker, and p < 0.001 for comparison of current smoker versus never and former smoker). Moreover, compared to participants who never smoked throughout life (41.6 [41.3-41.9] HU), current smokers (40.4 [39.9-40.9] HU) and former smokers (40.8 [40.5-41.2] HU) had lower lean muscle attenuation suggesting lower muscle quality in the fully adjusted model (p < 0.001 for comparison of never smokers with either of the other two strata). Among participants who had ever smoked, pack-years of smoking exposure were directly associated with IMAT volume (β [95% CI]: 0.017 [0.010-0.025]) (p < 0.001). Despite having less SAT, current smokers also had higher VAT/SAT ratio than never smokers. These findings must be viewed with caution as residual confounding and/or reverse causation may contribute to these associations.
CONCLUSIONS - We found that, compared to those who never smoked, current and former smokers had abdominal muscle composition that was higher in adipose tissue volume, a finding consistent with higher CVD risk and age-related physical deconditioning. These findings challenge the belief that smoking-associated weight loss or maintenance confers a health benefit.
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17 MeSH Terms
Antimüllerian hormone and F2-isoprostanes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
Kim C, Slaughter JC, Terry JG, Jacobs DR, Parikh N, Appiah D, Leader B, Moravek MB, Wellons MF
(2020) Fertil Steril 114: 646-652
MeSH Terms: Adult, African Americans, Age Factors, Anti-Mullerian Hormone, Biomarkers, Cross-Sectional Studies, European Continental Ancestry Group, F2-Isoprostanes, Female, Humans, Ovarian Reserve, Oxidative Stress, United States
Show Abstract · Added July 20, 2020
OBJECTIVE - To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimüllerian hormone (AMH), an indicator of ovarian reserve, in a population-based cohort of women of black and white ethnicities.
DESIGN - Cross-sectional analysis.
SETTING - Not applicable.
PATIENTS - The CARDIA Women's Study, a population-based cohort. Black (n = 398) and white (n = 432) late reproductive-aged women (mean age 40 ± 3.6 years) without histories of gynecologic surgery.
MAIN OUTCOME MEASURES - Log-transformed serum AMH concentrations.
RESULTS - Linear regression models evaluated whether plasma F2-isoprostanes were associated with log-transformed AMH after adjustment for age, race, smoking, body mass index, and oral contraceptive pill use. Higher levels of F2-isoprostanes were associated with lower AMH levels (β -0.048 per standard deviation, 95% confidence interval -0.087, -0.01). The observed associations were stronger at younger ages (P=.04 for interaction between levels of age and F2-isoprostanes). Indicators of other steps in the oxidative stress pathway (superoxide dismutase, paraoxonase activity, oxidized low-density lipoprotein cholesterol, and carotenoids) were not associated with AMH, although lower phospholipase A2 activity (β 0.036 per standard deviation, 95% confidence interval 0.001, 0.071) was associated with lower AMH across all ages.
CONCLUSION - In a population-based cohort, higher levels of F2-isoprostanes were associated with lower ovarian reserve, particularly at younger ages.
Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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13 MeSH Terms