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Perioperative cefazolin prescribing rates following suppression of alerts for non-IgE-mediated penicillin allergies
- Ashley Bogus, Kelley McGinnis, Joshua Vergin, Sara M. May, Richard J. Hankins, Erica Stohs, Trevor C. Van Schooneveld, Scott J. Bergman
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- Infection Control & Hospital Epidemiology , First View
- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-5
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Background:
Cefazolin is the preferred antimicrobial for the prevention of surgical site infections (SSIs) in many procedures. The presence of penicillin allergies can influence prescribing of alternative agents like vancomycin. In April 2022, Nebraska Medicine implemented a suppression of alerts for non-IgE-mediated and nonsevere penicillin allergies in the electronic medical record (EMR) upon cephalosporin prescribing. The objective of this study was to evaluate changes in perioperative cefazolin for SSI prophylaxis.
Methods:This was a quasi-experimental study of patients undergoing procedures for which cefazolin was the preferred agent per institutional guidance. Education on the change was distributed via e-mail to surgical staff and pharmacists. Pre- and post-intervention data were collected from April 2021 through March 2022 and April 11, 2022, through October 2022, respectively. Chart review was performed on patients with reported penicillin allergies for the top surgical procedures with <50% cefazolin utilization pre-intervention. The primary outcome was the administration of perioperative cefazolin in patients with penicillin allergies, including unknown reactions.
Results:A total of 6,676 patients underwent surgical procedures (pre-intervention n = 4,147, post-intervention n = 2,529). Documented penicillin allergies were similar between the pre- and post-intervention group (12.3% vs. 12.6%). In individuals with documented penicillin allergies, cefazolin prescribing increased from 49.6% to 74.3% (p < 0.01). Chart review for safety outcomes identified no difference in new severe reactions, rescue medication, SSIs, acute kidney injury, postoperative Clostridioides difficile infection, or methicillin-resistant Staphylococcus aureus infections.
Conclusion:Following the suppression of EMR alerts for non-IgE-mediated and nonsevere penicillin allergies, cefazolin prescribing rates for SSI prophylaxis significantly improved.
Attitudes, subjective norms and perceived behavioural control factors influencing Canadian secondary school students’ milk and milk alternatives consumption
- Carise M Thompson, Susan J Elliott, Samantha Meyer, Scott T Leatherdale, Shannon E Majowicz
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- Journal:
- Public Health Nutrition / Volume 27 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 08 March 2024, e92
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Objective:
The research objectives were to evaluate factors that influence Canadian secondary school students’ milk and milk alternatives (MMA) consumption and to explore associations through age and gender lenses.
Design:A qualitative design was used, consisting of semi-structured interviews and photo-elicitation methods. Analysis was guided by the Theory of Planned Behaviour (TPB). Deductive and inductive thematic analyses were used to generate themes, charting data based on attributes such as gender and age.
Setting:Interviews were held virtually or via telephone.
Participants:Participants were twenty-eight high school students from Ontario, Canada, diverse in terms of gender and age.
Results:Both desirable and undesirable beliefs about the health outcomes of consuming MMA were commonly discussed. These included health benefits such as strong bones, muscular strength, and growth, and health consequences like unwanted skin conditions, weight gain, and diseases. While boys and girls associated MMA consumption with muscular strength, boys predominantly considered this favourable, while girls discussed outcomes like unwanted skin conditions and weight gain more often. Adolescents’ perspectives on taste/perceived enjoyment, environmentally friendly choices and animal welfare also influenced their MMA preferences. Parental influences were most cited among social factors, which appeared to be stronger during early adolescence. Factors involving cost, time and accessibility affected adolescents’ beliefs about how difficult it was to consume MMA.
Conclusions:Recommendations for shifting attitudes towards MMA are provided to address unfavourable beliefs towards these products. Interventions to increase MMA consumption among adolescents should include parents and address cost barriers.
Methiozolin rate and application frequency influence goosegrass (Eleusine indica) and smooth crabgrass (Digitaria ischaemum) control in turf
- John M. Peppers, J. Scott McElroy, Pawel M. Orlinski, James Baird, Pawel Petelewicz, Mikerly M. Joseph, I. Alejandra Sierra-Augustinus, Marco Schiavon, Shawn D. Askew
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- Journal:
- Weed Technology / Volume 38 / 2024
- Published online by Cambridge University Press:
- 06 February 2024, e24
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Methiozolin is labeled for goosegrass and smooth crabgrass control in golf course putting greens, but no peer-reviewed literature exists regarding this use. Greenhouse experiments were conducted evaluating goosegrass and smooth crabgrass response to increasing rates of methiozolin as affected by weed growth stage. In general, as weed growth stage increased, the methiozolin rate required to reduce weed biomass 90% (WR90) increased. Goosegrass was more sensitive to preemergence-applied methiozolin than smooth crabgrass, and the WR90 was 30.4 and 118 g ai ha–1 for goosegrass and smooth crabgrass, respectively. However, smooth crabgrass was generally more sensitive to postemergence-applied methiozolin than goosegrass. Subsequent field studies were conducted to evaluate goosegrass and smooth crabgrass control with methiozolin applied singularly or sequentially at standard preemergence timings. Results indicated methiozolin applied singularly or sequentially at the label-recommended rate (500 g ha–1) is not persistent enough to provide season-long control of goosegrass and smooth crabgrass. Ten field studies were conducted in Alabama, California, Florida, and Virginia to evaluate frequent methiozolin application programs with the objective of providing selective, season-long goosegrass and smooth crabgrass control. Results from these studies indicate methiozolin can be safely applied to hybrid bermudagrass and creeping bentgrass putting greens despite exceeding the yearly maximum use rate for putting greens (2,500 g ha–1) with some treatments. Methiozolin effectively controlled smooth crabgrass throughout the growing season in California and Virginia when 10 biweekly applications were applied at 250 g ha–1 or higher. In Florida, methiozolin did not acceptably (80%) control goosegrass regardless of application rate. In Virginia, methiozolin acceptably controlled goosegrass only when applied at rates and frequencies that exceeded the maximum yearly methiozolin usage rate. These data indicate that methiozolin has the potential to control smooth crabgrass preemergence when applied frequently, but does not provide acceptable goosegrass control at labeled rates.
Species discrimination in the multituberculate Mesodma Jepsen, 1940 (Mammalia, Allotheria): considerations of size, shape, and form
- Austin J. Ashbaugh, Craig S. Scott, Gregory P. Wilson Mantilla, Jessica M. Theodor
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- Journal:
- Journal of Paleontology / Volume 97 / Issue 6 / November 2023
- Published online by Cambridge University Press:
- 03 January 2024, pp. 1282-1292
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Although knowledge of their fossil record continues to improve, multituberculates nonetheless remain one of the more poorly understood mammalian clades, which can be attributed to a record comprised of isolated teeth and fragmentary jaws. Fortunately, the p4 of multituberculates is the most common form of remains for this group and is a principal source of diagnostic characters in systematic studies, the p4 of cimolodontan multituberculates is both common and a source of diagnostic characters in systematic studies. The results of a recent morphometric study on the neoplagiaulacid Mesodma suggest that p4 size may be more useful than shape in diagnosing the various species referred to this genus. We tested this hypothesis by applying two different morphometric methods (2D geometric morphometrics and linear measurements) to two samples: (1) one including the p4s of four known species of Mesodma (M. ambigua, M. thompsoni, M. formosa, and M. pygmaea), and (2) a sample of unidentified p4s of Mesodma from the Bug Creek Anthills locality of northeastern Montana. Our results indicate that while form explains most of the morphological variation in p4s of the various species of Mesodma, linear-measurement data support differences in p4 morphology that are not recovered by form data alone. Depending on the methods used, we found evidence for the presence of one or more species of Mesodma in the Bug Creek Anthills fauna. Although shape and size both contribute to morphological variation in the p4 of Mesodma, our results suggest that the diagnostic power of each varies with the type of methodology employed.
Synthesis of Al-PILC Assisted by Ultrasound: Reducing the Intercalation Time and the Amount of Synthesis Water
- M. Josefina Pérez-Zurita, Gabriela J. Pérez-Quintana, Alfonso J. Hasblady, Adriana Maldonado, Caribay Urbina de Navarro, Ander De Abrisqueta, Carlos E. Scott
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- Journal:
- Clays and Clay Minerals / Volume 53 / Issue 5 / October 2005
- Published online by Cambridge University Press:
- 01 January 2024, pp. 528-535
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Of all the known pillared layered clays (PILC), Al-PILC is the most studied. In spite of that, its use on a commercial scale is not yet possible due to the large amount of water required for its synthesis. The aim of the present work was to take advantage of the beneficial effects of ultrasound radiation for reducing intercalation time, and to optimize the synthesis parameters in order to find a viable industrial means of preparing Al-PILC.
A comprehensive study of the effect of ultrasonic radiation on the parameters which have a direct effect on the amount of water used in the synthesis was conducted, specifically on the effects of: (1) mmol of Al/g of clay ratio (R) by decreasing the volume of A1 solution and keeping the amount of clay constant, (2) the concentration of clay in the initial suspension (or not suspending the clay at all), and (3) the concentration of the A1 precursor solution. The use of ultrasonic radiation produced the expected reduction in exchange time which was attributed to a decrease of the clay-particle size. This decrease of particle size gave rise to an improvement in the diffusion of the A1 precursor towards the core of the clay grain leading to solids with increased surface areas, basal spacing and X-ray diffraction peak definition. By optimizing the synthesis parameters directly involved in the consumption of water, it was possible to decrease the amount used by >60%.
46 Cognitive Reserve and Gait Speed are Associated with Cognitive Performance in Black/African American Older Adults
- Matthew J Stauder, Kelly J Hiersche, Scott M Hayes
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 354-355
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Objective:
Cognitive reserve and health-related fitness are associated with favorable cognitive aging, but Black/African American older adults are underrepresented in extant research. Our objective was to explore the relative contributions and predictive value of cognitive reserve and health-related fitness metrics on cognitive performance at baseline and cognitive status at a 4-year follow up in a large sample of Black/African American older adults.
Participants and Methods:Participants aged 65 years and older from the Health and Retirement Study (HRS) who identified as Black/African American and completed baseline and follow-up interviews (including physical, health, and cognitive assessments) were included in the study. The final sample included 321 Black/African American older adults (mean age = 72.8; sd = 4.8; mean years of education = 12.3; sd = 2.9; mean body mass index (BMI) = 29.1; sd = 5.2; 60.4% identified as female). A cross-sectional analysis of relative importance – a measure of partitioned variance controlling for collinearity and model order – was first used to explore predictor variables and inform the hierarchical model order. Next, hierarchical multiple regression was used to examine cross-sectional relationships between cognitive reserve (years of education), health-related fitness variables (grip strength, lung capacity, gait speed, BMI), and global cognition. Multiple logistic regression was used to examine prospective relationships between predictors and longitudinal cognitive status (maintainers versus decliners). Control variables in all models included age, gender identity, and a chronic disease index score.
Results:Cross-sectional relative importance analyses identified years of education and gait speed as important predictors of global cognition. The cross-sectional hierarchical regression model explained 33% of variance in baseline global cognition. Education was the strongest predictor of cognitive performance (β = 0.48, p < 0.001). Holding all other variables constant, gait speed was significantly associated with baseline cognitive performance and accounted for a significant additional amount of explained variance (ΔR = 0.01, p = 0.032). In a prospective analysis dividing the sample into cognitive maintainers and decliners, a single additional year of formal education increased chances of being classified as a cognitive maintainer (OR = 1.30, 95% CI = 1.17-1.45). There were no significant relationships between rate of change in health-related fitness and rate of change in cognition.
Conclusions:Education, a proxy for cognitive reserve, was a robust predictor of global cognition at baseline and was associated with increased odds of maintaining cognitive ability at 4-year follow up in Black/African American older adults. Of the physical performance metrics, gait speed was associated with cognitive performance at baseline. The lack of observed association between other fitness variables and cognition may be attributable to the brief assessment procedures implemented in this large-scale study.
8 Perspectives of Self, Stigma, and the Future Following Alzheimer's Disease Biomarker Disclosure in Cognitively Symptomatic Older Adults
- Annalise Rahman-Filipiak, Mary Lesniak, Marie Milliken, Sara Feldman, J. Scott Roberts, Benjamin M Hampstead
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 219-221
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Objective:
In the absence of treatments to halt or reverse symptoms of Alzheimer's disease, early detection may extend the window for meaningful treatment, advanced planning, and coping. Positron emission tomography (PET) scans for amyloid and tau are validated biomarkers of AD, yet results are rarely disclosed to participants due to concerns about negative impacts. While prior studies suggest limited anxiety, depression, or suicidality following biomarker disclosure, no study to date has examined broader psychological impacts of PET amyloid/tau disclosure to symptomatic individuals. Therefore, we explored post-disclosure changes in future time perspective (perceptions of limited time or possibilities left in the future), self-efficacy for managing symptoms, and perceived stigma as a function of result received.
Participants and Methods:Forty-three older adults (age = 72.0±6.2 years; education = 16.5±2.6; 88.4% White Non-Hispanic; 48.8% female) participated in the study, of whom 62.8% were diagnosed with mild cognitive impairment (MCI) and the remainder with Dementia of the Alzheimer's type. All participants underwent pre-disclosure biomarker education and decisional capacity assessment, followed by baseline measures. Participants demonstration decisional capacity completed an interactive disclosure session during which they received dichotomous results of their research positron emission tomography (PET) scans for amyloid and tau (elevated versus not elevated for each biomarker). Findings were discussed in relation to presence/absence of Alzheimer's disease, the etiology of their cognitive difficulties, and risk for conversion or further decline. At baseline, immediately following disclosure, and at 1-week follow-up, participants completed several questionnaires: the Future Time Perspective (FTP) scale, a measure of how much the participant sees time as limited, the Self Efficacy for Managing Chronic Disease scale (SECD), and the Stigma Scale for Chronic Illness (SSCI-8), all of which were modified to apply to Alzheimer's disease and associated experiences.
Results:The main effects of time (F=1.10, p=.334, A?p2=.026), biomarker status (F(1)=3.10, p=.086, Ajp2=.070), and the time by biomarker status interaction (F=0.39, p=.661, Ajp2=.009) on FTP score was not significant. Though neither time (F=0.07, p=.933, A?p2=.002) nor the time by biomarker status interaction (F=2.16, p=.122, Ajp2=.050) effect on SECD was significant, being biomarker positive (A+T-/A+T+) was associated with lower self-efficacy (F(1)=5.641, p=.022, Ajp2=.121). Neither main effect for time (F=0.15, p=.853, Ajp2=.004) or biomarker status (F(1)=0.35, p=.558, A?p2=.009) on SSCI-8 was significant. The time by biomarker status interaction was significant (f=4.27, p=.018, =.096), such that biomarker negative participants experience a transient increase in perceived stigma directly after disclosure that resolves one week later, and biomarker negative participants experience the opposite pattern.
Conclusions:Findings suggest that individuals who receive biomarker positive results may feel less competent to manage their symptoms compared to those who are biomarker negative, emphasizing the need for post-disclosure interventions targeting self-efficacy. The effect of disclosure on perceptions of time being limited and on perceived stigma were minimal, even when those results indicate evidence of Alzheimer's disease and risk for clinical progression. These results further support the safety of biomarker disclosure procedures. Future studies should provide longer-term assessment of psychological, behavioral, and clinical outcomes following Alzheimer's disease biomarker disclosure.
57 CSF Markers of AD-Related Pathology Relate to aMCI among People with HIV
- Judith D. Lobo, Erin E. Sundermann, Laura M. Campbell, Ben Gouaux, Scott Letendre, Mark W. Bondi, David J. Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 53-54
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Objective:
Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels
Participants and Methods:Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.
Results:58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.
Conclusions:Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.
41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV
- Maulika Kohli, Laura M Campbell, Erin Sundermann, Mark W Bondi, Paul Gilbert, Donald Franklin, Scott Letendre, Robert K Heaton, Payal Patel, Susan Morgello, Benjamin Gelman, David Clifford, Raeanne C Moore, David J Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 249-250
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Objective:
Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.
Participants and Methods:283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.
Results:Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).
Conclusions:PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.
40 Positive and Negative Emotional Outcomes Following Alzheimer’s Disease Biomarker Disclosure in Cognitively Symptomatic Older Adults
- Mary R. Lesniak, Marie Milliken, Sara Feldman, Scott J. Roberts, Benjamin M. Hampstead, Annalise M. Rahman-Filipiak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 248-249
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Objective:
There are many potential benefits of early identification of those with Alzheimer’s disease (AD), including more opportunity for early intervention to slow AD progression (e.g., treatment, lifestyle changes, etc.) and to plan for the future. Positron emission tomography (PET) scans for abnormal amyloid and tau are commonly conducted in research settings. Despite strong interest in learning AD biomarker results, participants rarely receive their research data, in part due to concern about the possibility of undue distress based on results. We aimed to explore both positive and negative emotional reactions following PET biomarker disclosure as a function of result received.
Participants and Methods:Forty-three older adults (age = 72.0±6.21 years, education = 16.5±2.62 years, 49% Female, 88% White Non-Hispanic) completed PET amyloid and tau testing and disclosure. Sixty-three percent were diagnosed with mild cognitive impairment (MCI) while the remainder of participants were diagnosed with Dementia Alzheimer’s type (DAT). Participants completed pre-disclosure biomarker education and a decisional capacity assessment followed by baseline measures. Participants then completed a disclosure session where they received personal PET amyloid and tau results on an elevated vs. not elevated scale for each ligand. Results were discussed in relation to presence/absence of Alzheimer’s disease, how the result relates to their cognitive difficulties, and risk of developing Dementia-Alzheimer’s Type. At baseline (pre-disclosure), immediately post-disclosure, and 1-week post-disclosure, participants completed the Beck Anxiety Inventory (BAI), The Geriatric Depression Scale - 15 Item (GDS-15), Impact of Neuroimaging in AD (INI-AD) Scale, and the Positive and Negative Affective Scale - Short Form (PANAS-SF). All questionnaires were modified to apply to Alzheimer’s disease and related experiences.
Results:Of the 43 participants who participated in disclosure, 74% received biomarker positive results (either A+T- or A+T+); all others were biomarker negative. We conducted a series of mixed analysis of variance (ANOVA) tests to determine the effect of disclosure and biomarker status for each of the outcomes of interest. Neither the effect of time nor the time by biomarker status interaction was significant for any of the outcomes (all p>.05). The main effect of biomarker status was significant for BAI (F(1)=5.12, p=.031, n,p2=.146) and INI-AD Distress (F(1)=12.70, p=.001, np2=.241) and Positive (F(1)=34.57, p<.001, np2=.464) subscale scores with A+T-/A+T+ participants reporting higher negative affect than those who were A-/T-; however, even among biomarker positive individuals, scores did not exceed clinical thresholds. GDS-15, PANAS-Negative and Positive Subscale scores did not differ significantly by biomarker status (all p>.05) and no significant adverse events occurred following disclosure. Additionally, no participants cited regret about receiving their results.
Conclusions:While disclosure of biomarker positivity may result in mild increases in acute anxiety or distress, or fewer positive emotions, it does not result in clinically significant emotional reactions and was not associated with regret. Overall, findings are consistent with literature indicating safety of biomarker disclosure procedures for symptomatic individuals. Future research should follow participants over longer periods to evaluate the impacts of biomarker disclosure.
3 Development of a Computerized Neurocognitive Battery for Children and Adolescents Affected by Human Immunodeficiency Virus in Botswana
- J. Cobb Scott, Tyler M Moore, Amelia E Van Pelt, Mogomotsi Matshaba, Ontibile Tshume, Onkemetse Phoi, Boitumelo Thuto, Ruben C Gur, Elizabeth D Lowenthal
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 211-212
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Objective:
Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamlines evaluation of neurocognitive functioning. Our group translated and culturally adapted the PennCNB for use among children and adolescents in this high-burden, low-resource setting. The current study examined the construct validity and sensitivity to HIV infection and exposure of the culturally adapted PennCNB among a cohort of HIV-affected children and adolescents in Gaborone, Botswana.
Participants and Methods:628 school-aged children aged 7-17 years (n=223 children living with HIV [HIV+]; n=204 HIV exposed, uninfected [HEU]; and 201 HIV unexposed, uninfected [HUU]) completed the PennCNB. Participants were recruited from a clinic specializing in the care and treatment of HIV+ children and adolescents in Gaborone, Botswana, as well as from local schools. Confirmatory factor analyses were performed on efficiency measures for 13 PennCNB tests. Multiple regressions examined associations between HIV and neurocognitive functioning while controlling for age and sex. Multivariate normative comparisons were used to examine rates of overall cognitive impairment by comparing individual profiles of test scores to the multivariate distribution of test scores using age-normed data from the HUU group.
Results:Confirmatory factor analysis supported four hypothesized neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. As expected, there were main effects of age on cognitive performance across all domains (ps < .001), and there were small sex differences, with females performing better in executive functioning and males performing better on visuospatial processing. Children and adolescents living with HIV performed significantly worse than HUU across all domains (ps < .001), with the largest effect sizes on measures of abstraction, working memory, and processing speed. HEU also performed worse than HUU across several domains, with smaller effect sizes. Multivariate normative comparisons indicated that 27% of the HIV+ group evidenced global neurocognitive impairment.
Conclusions:Overall, results support the validity of a neurocognitive battery adapted for use in Botswana, a non-Western, resource-limited setting. Results indicated that the adapted battery applied to children and adolescents with limited computer familiarity had a similar factor structure as in Western settings, indicating that the PennCNB appeared to assess the hypothesized neurocognitive domains. Hypothesized associations with age and sex supported the battery’s construct validity. Moreover, the battery appears to be sensitive to cognitive impairments associated with perinatally-acquired HIV and in utero HIV-related exposures, as it discriminated between the HUU, HIV+, and HEU groups. Differences were found in specific domains and in detection of overall impairment, including approximately one quarter of children and adolescents living with HIV in this cohort evidencing global neurocognitive impairment. Together, these results provide evidence that the PennCNB could serve as a useful tool for the assessment of neurocognitive functioning in school-aged children and adolescents from Botswana and, potentially, other resource-limited settings.
4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition
- Jeffrey M Rogers, Igor Grant, Maria Cecilia Marcondes, Erin E Morgan, Mariana Cherner, Ronald J Ellis, Scott L Letendre, Robert K Heaton, Jennifer E Iudicello
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 797-798
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Objective:
Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.
Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.
Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.
Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
11 - The News Media and the Politics of Inequality in Advanced Democracies
- from Part III - Voters and Demand for Redistribution
- Edited by Noam Lupu, Vanderbilt University, Tennessee, Jonas Pontusson, Université de Genève
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- Book:
- Unequal Democracies
- Published online:
- 07 December 2023
- Print publication:
- 21 December 2023, pp 245-275
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Summary
What has allowed inequalities in material resources to mount in advanced democracies? This chapter considers the role of media reporting on the economy in weakening accountability mechanisms that might otherwise have incentivized governments to pursue more equal outcomes. Building on prior work on the United States, we investigate how journalistic depictions of the economy relate to real distributional developments across OECD countries. Using sentiment analysis of economic news content, we demonstrate that the evaluative content of the economic news strongly and disproportionately tracks the fortunes of the very rich and that good (bad) economic news is more common in periods of rising (falling) income shares at the top. We then propose and test an explanation in which pro-rich biases in news tone arise from a journalistic focus on the performance of the economy in the aggregate, while aggregate growth is itself positively correlated with relative gains for the rich. The chapter’s findings suggest that the democratic politics of inequality may be shaped in important ways by the skewed nature of the informational environment within which citizens form economic evaluations.
88 Light and Vigorous Bouts of Acute Aerobic Exercise Positively Impact Sustained Attention and Inhibition but not Pattern Separation in Young Adults
- Michael A. Melville, Jessica Stark, Kelly J. Hiersche, Michael Esterman, Scott M. Hayes
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 288-289
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Objective:
The current study had two primary objectives: 1) To assess the dose-response relationship between acute bouts of aerobic exercise intensity and performance in multiple cognitive domains (episodic memory, attention, and executive function) and 2) To replicate and extend the literature by examining the dose-response relationship between aerobic exercise intensity and pattern separation.
Participants and Methods:18 young adults (mean age = 21.6, sd = 2.6; mean education = 13.9, sd = 3.4; 50% female) were recruited from The Ohio State University and surrounding area (Columbus, OH). Participants completed control (no exercise), light intensity, and vigorous intensity exercise conditions across three counterbalanced appointments. For each participant, all three appointments occurred at approximately the same time of day with at least 2 days between appointments. Following the rest or exercise conditions and after an approximately 7 minute delay, participants completed a Mnemonic Similarity Task (MST; Stark et al., 2019) to assess pattern separation. This task was always administered first as we attempted to replicate previous studies and further clarify the relationship between acute bouts of aerobic exercise and pattern separation by implementing an exercise stimulus that varied in intensity. After the MST, three brief cognitive tasks (roughly 5 min each) were administered in a counterbalanced order: a gradual-onset continuous performance task (gradCPT; Esterman et al., 2013), the flanker task from the NIH toolbox, and a face-name episodic memory task. Here we report results from the gradCPT, which assesses sustained attention and inhibitory control. Heart rate and ratings of perceived exertion were collected to validate the rest and exercise conditions. Repeated-measures ANOVAs were used to assess the relationship between exercise condition and dependent measures of sustained attention and inhibitory control and pattern separation.
Results:One-way repeated-measures ANOVAs revealed a main effect of exercise condition on gradCPT task performance for task discrimination ability (d') and commission error rate (p’s < .05). Pairwise comparisons revealed task discrimination ability was significantly higher following the light intensity exercise condition versus the control condition. Commission error rate was significantly lower for both the light and vigorous exercise conditions compared to the control condition. For the MST, two-way repeated-measures ANOVAs revealed an expected significant main effect of lure similarity on task performance; however, there was not a significant main effect of exercise intensity on task performance (or a significant interaction).
Conclusions:The current study indicated that acute bouts of exercise improve both sustained attention and inhibitory control as measured with the gradCPT. We did not replicate previous work reporting that acute bouts of exercise improve pattern separation in young adults. Our results further indicate that vigorous exercise did not detrimentally impact or improve pattern separation performance. Our results indicate that light intensity exercise is sufficient to enhance sustained attention and inhibitory control, as there were no significant differences in performance following light versus vigorous exercise.
30 Exploring the Differential Importance of Modifiable Fitness Variables on Cognitive Performance in Older Adults
- Jessica H Stark, Kelly J Hiersche, Scott M Hayes
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 341-342
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Objective:
To identify the relative contributions and importance of modifiable fitness and demographic variables to cognitive performance in a cohort of healthy older adults.
Participants and Methods:Metrics of modifiable fitness (gait speed, respiratory function, grip strength, and body mass index (BMI)) and cognition (executive function, episodic memory, and processing speed) were assessed in 619 older adults from the Health and Retirement Study 2016 wave (mean age = 74.9, sd = 6.9; mean education = 13.4 years, sd = 2.6; 42% female). General linear models were employed to assess the contribution of modifiable fitness variables in predicting three domains of cognition: executive function, episodic memory, and processing speed. Demographics (age, sex, education, time between appointments, and a chronic disease score) were entered as covariates for each model. Relative importance metrics were computed for all variables in each model using Lindeman, Merenda, and Gold (lmg) analysis, a technique which decomposes a given model’s explained variance to describe the average contribution of each predictor variable, independent of its position in the linear model.
Results:When all variables were entered into the general linear model, demographic and modifiable fitness variables explained 35%, 24%, and 26% of the variance in executive function, episodic memory, and processing speed, respectively (all three models were significant, p <0.001). Age, education, respiratory function, and walking speed had higher relative importance values (all lmgs > 1.8) compared to BMI, grip strength, and other covariates in all three models (all lmgs < 1.3). Gender was also relatively important in the executive function (lmg = 4.2) and episodic memory models (lmg = 5.0). Of the modifiable fitness variables, walking speed and respiratory function had the greatest lmg values (5.8 and 6.4 respectively) in the executive function model, similar to demographic variables age (lmg = 6.0) and education (lmg = 8.9). When demographic variables were entered as covariates, modifiable fitness variables collectively accounted for an additional 9.7%, 6.3%, and 6.0% variance in the executive function, episodic memory, and processing speed models respectively (all three models were significant, p <0.001).
Conclusions:Our findings indicate that walking speed and respiratory function are of similar importance compared to “traditional” demographic variables such as age and education in predicting cognitive performance in a cohort of healthy older adults. Moreover, modifiable fitness variables accounted for unique variance in executive function, episodic memory, and processing speed after accounting for age and education. Modifiable fitness variables explained the most unique variance in executive function. These results extend the current literature by demonstrating that modifiable fitness variables, even when assessed with brief and relatively coarse measures of physical performance, may be useful in predicting cognitive function. Moreover, the results highlight the need to assess metrics of cognitive reserve, such as education, as well as modifiable fitness variables and their respective roles in accounting for cognitive performance. The data further suggest that relative contributions of physical performance metrics may vary by cognitive domain in healthy older adults.
A Novel Algorithm for Improving the Prehospital Diagnostic Accuracy of ST-Segment Elevation Myocardial Infarction
- Mat Goebel, Lauren M. Westafer, Stephanie A. Ayala, El Ragone, Scott J. Chapman, Masood R. Mohammed, Marc R. Cohen, James T. Niemann, Marc Eckstein, Stephen Sanko, Nichole Bosson
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- Journal:
- Prehospital and Disaster Medicine / Volume 39 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 04 December 2023, pp. 37-44
- Print publication:
- February 2024
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Introduction:
Early detection of ST-segment elevation myocardial infarction (STEMI) on the prehospital electrocardiogram (ECG) improves patient outcomes. Current software algorithms optimize sensitivity but have a high false-positive rate. The authors propose an algorithm to improve the specificity of STEMI diagnosis in the prehospital setting.
Methods:A dataset of prehospital ECGs with verified outcomes was used to validate an algorithm to identify true and false-positive software interpretations of STEMI. Four criteria implicated in prior research to differentiate STEMI true positives were applied: heart rate <130, QRS <100, verification of ST-segment elevation, and absence of artifact. The test characteristics were calculated and regression analysis was used to examine the association between the number of criteria included and test characteristics.
Results:There were 44,611 cases available. Of these, 1,193 were identified as STEMI by the software interpretation. Applying all four criteria had the highest positive likelihood ratio of 353 (95% CI, 201-595) and specificity of 99.96% (95% CI, 99.93-99.98), but the lowest sensitivity (14%; 95% CI, 11-17) and worst negative likelihood ratio (0.86; 95% CI, 0.84-0.89). There was a strong correlation between increased positive likelihood ratio (r2 = 0.90) and specificity (r2 = 0.85) with increasing number of criteria.
Conclusions:Prehospital ECGs with a high probability of true STEMI can be accurately identified using these four criteria: heart rate <130, QRS <100, verification of ST-segment elevation, and absence of artifact. Applying these criteria to prehospital ECGs with software interpretations of STEMI could decrease false-positive field activations, while also reducing the need to rely on transmission for physician over-read. This can have significant clinical and quality implications for Emergency Medical Services (EMS) systems.
GWAS of Dizygotic Twinning in an Enlarged Australian Sample of Mothers of DZ Twins
- Scott D. Gordon, David L. Duffy, David C. Whiteman, Catherine M. Olsen, Kerrie McAloney, Jessica M. Adsett, Natalie A. Garden, Simone M. Cross, Susan E. List-Armitage, Joy Brown, Jeffrey J. Beck, Hamdi Mbarek, Sarah E. Medland, Grant W. Montgomery, Nicholas G. Martin
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- Journal:
- Twin Research and Human Genetics / Volume 26 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 23 November 2023, pp. 327-338
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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
Rise of the (possible) resistance: a review of susceptibility patterns for nontyphoidal Salmonella enterica in Nebraska
- Shawnalyn W. Sunagawa, Catherine Christopherson, Scott J. Bergman, Molly M. Miller, Mackenzie R. Keintz, Taylor A. Wahlig, Paul Fey, Trevor C. Van Schooneveld
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 3 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 23 October 2023, e181
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Our institution sought to evaluate our antimicrobial stewardship empiric treatment recommendations for Salmonella. Results from 36 isolates demonstrated reduced susceptibilities to fluoroquinolones with 1 isolate susceptible only to ceftriaxone. Analysis supports the current recommendation of empiric ceftriaxone therapy for severe infection and updated recommendation for sulfamethoxazole-trimethoprim in non-severe infections.
What is the true nature of the relationship between metabolic disturbance, specifically of glucose and insulin metabolism, and depressive and other mood disorders?
- Elizabeth M. Scott, Ian B. Hickie, Jacob J. Crouse, Mirim Shin
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- Journal:
- Research Directions: Depression / Volume 1 / 2024
- Published online by Cambridge University Press:
- 11 October 2023, e2
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Much attention in recent years has focused on the extent to which the risk of metabolic disturbances, and most fundamentally of glucose and insulin, are prevalent among those treated for depressive and other mood disorders (Osimo et al., 2021; Scott et al., 2019; Tickell et al., 2022). Public concern has also focused on the increased rates of premature mortality in those with chronic depression and other major mental disorders, with a significant proportion of that risk being due to early-onset cardiovascular disease (particularly among women). A common assumption is that much of this risk is a consequence of medical treatments for depression, and their possible adverse effects such as increased risk of diabetes, presumably mediated by long-term weight gain.