Publications by authors named "Elizabeth Moore"

260 Publications

The relationship between white matter microstructure and self-perceived cognitive decline.

Neuroimage Clin 2021 Aug 28;32:102794. Epub 2021 Aug 28.

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Subjective cognitive decline (SCD) is a perceived cognitive change prior to objective cognitive deficits, and although it is associated with Alzheimer's disease (AD) pathology, it likely results from multiple underlying pathologies. We investigated the association of white matter microstructure to SCD as a sensitive and early marker of cognitive decline and quantified the contribution of white matter microstructure separate from amyloidosis. Vanderbilt Memory & Aging Project participants with diffusion MRI data and a 45-item measure of SCD were included [n = 236, 137 cognitively unimpaired (CU), 99 with mild cognitive impairment (MCI), 73 ± 7 years, 37% female]. A subset of participants (64 CU, 40 MCI) underwent a fasting lumbar puncture for quantification of cerebrospinal fluid (CSF) amyloid-β(CSF Aβ), total tau (CSF t-tau), and phosphorylated tau (CSF p-tau). Diffusion MRI data was post-processed using the free-water (FW) elimination technique, which allowed quantification of extracellular (FW) and intracellular compartment (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) microstructure. Microstructural values were quantified within 11 cognitive-related white matter tracts, including medial temporal lobe, frontal transcallosal, and fronto-parietal tracts using a region of interest approach. General linear modeling related each tract to SCD scores adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile scores, APOE ε4 carrier status, diagnosis, Geriatric Depression Scale scores, hippocampal volume, and total white matter volume. Competitive models were analyzed to determine if white matter microstructural values have a unique role in SCD scores separate from CSF Aβ. FW-corrected radial diffusivity (RD) was related to SCD scores in 8 tracts: cingulum bundle, inferior longitudinal fasciculus, as well as inferior frontal gyrus (IFG) pars opercularis, IFG orbitalis, IFG pars triangularis, tapetum, medial frontal gyrus, and middle frontal gyrus transcallosal tracts. While CSF Aβ was related to SCD scores in our cohort (R = 39.03%; β = -0.231; p = 0.020), competitive models revealed that fornix and IFG pars triangularis transcallosal tract RD contributed unique variance to SCD scores beyond CSF Aβ (R = 44.35% and R = 43.09%, respectively), with several other tract measures demonstrating nominal significance. All tracts which demonstrated nominal significance (in addition to covariates) were input into a backwards stepwise regression analysis. ILF RD, fornix RD, and UF FW were best associated with SCD scores (R = 46.69%; p = 6.37 × 10). Ultimately, we found that medial temporal lobe and frontal transcallosal tract microstructure is an important driver of SCD scores independent of early amyloid deposition. Our results highlight the potential importance of abnormal white matter diffusivity as an early contributor to cognitive decline. These results also highlight the value of incorporating multiple biomarkers to help disentangle the mechanistic heterogeneity of SCD as an early stage of cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414539PMC
August 2021

Exploring the Impact of the Occupational Therapy Health and Wellness Program (OT-HAWP) on Performance and the Health-Related Quality of Life of Cancer Survivors.

Occup Ther Health Care 2021 Aug 30:1-16. Epub 2021 Aug 30.

Cancer Support Community, Indianapolis, IN, USA.

Creating innovative community-based programs for those living with and beyond cancer has the potential to improve outcomes; however, little has been done to explore these programs with participants that have various cancer diagnoses. We evaluated the impact of a 4-week community Occupational Therapy Health and Wellness Program (OT-HAWP) on self-perceived satisfaction and performance of daily activities, health-related quality of life, sleep quality, and fatigue among adults living with and beyond various cancer diagnoses. An uncontrolled, prospective, one-group pretest-posttest design was used. Participants completed patient reported measures of occupational performance and satisfaction (Canadian Occupational Performance Measure [COPM]), global health related quality of life (Patient-Reported Outcomes Measurement Information System-Global Health [PROMIS® Global Health]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), and the effect of fatigue on activities (Multidimensional Assessment of Fatigue [MAF]) before and after the program completion. Data was fully collected on 34 participants with various cancer diagnoses. For all outcomes, there was a statistically significant improvement after participating in the OT-HAWP program. Effect sizes range from small (0.46) to large (1.28). The OT-HAWP has the potential to improve self-reported occupational performance and satisfaction, global health-related quality of life, sleep quality, and fatigue in adults living with and beyond cancer in the community. Efficacy studies exploring community-based interventions are warranted to support legislation for improved access to care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07380577.2021.1943595DOI Listing
August 2021

Responses of Manduca sexta larvae to heat waves.

J Exp Biol 2021 04 6;224(7). Epub 2021 Apr 6.

Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

Climate change is increasing the frequency of heat waves and other extreme weather events experienced by organisms. How does the number and developmental timing of heat waves affect survival, growth and development of insects? Do heat waves early in development alter performance later in development? We addressed these questions using experimental heat waves with larvae of the tobacco hornworm, Manduca sexta. The experiments used diurnally fluctuating temperature treatments differing in the number (0-3) and developmental timing (early, middle and/or late in larval development) of heat waves, in which a single heat wave involved three consecutive days with a daily maximum temperature of 42°C. Survival to pupation declined with increasing number of heat waves. Multiple (but not single) heat waves significantly reduced development time and pupal mass; the best models for the data indicated that both the number and developmental timing of heat waves affected performance. In addition, heat waves earlier in development significantly reduced growth and development rates later in larval development. Our results illustrate how the frequency and developmental timing of sublethal heat waves can have important consequences for life history traits in insects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jeb.236505DOI Listing
April 2021

Recovery and Its Dynamics of Filamentous Fungi from Clinical Specimen Cultures: An Extensive Study.

Microbiol Spectr 2021 Sep 4;9(1):e0008021. Epub 2021 Aug 4.

Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA.

The culture method remains vital in diagnosing fungal infections, but extensive data-based evaluation of the method, especially for filamentous fungi (molds), is minimal. The purpose of this study was to characterize mold recoveries from fungal cultures and the impact of media and incubation duration. Clinical specimens for fungal cultures were submitted primarily from the eastern and central United States, and mold isolation data were prospectively collected and analyzed. A total of 1,821 molds in 59 genera were isolated from 1,687 positive specimens, accounting for approximately 5.6% of our cohort of 30,000 fungal cultures. Within 2 weeks, nearly 90% of molds and 97.3% of Aspergillus fumigatus complex were recovered (>95% confidence interval [CI]). All fungi were recovered within 11 days of incubation. The recovery peak time was day 3 for fungi, day 4 for hyaline molds, day 5 for dematiaceous molds, and day 7 for fungi. The recovery of Histoplasma capsulatum and species in the fourth week of incubation reveals that a 3-week incubation time is insufficient. Inhibitory mold agar was the best medium for recovering all mold types among all tested specimen types, yielding nearly 78% of mold growth overall, indicating the necessity of selective medium for fungal cultures. Fungal culture is the gold standard method of diagnosing fungal infections, but important information, such as the impact of media and incubation times on fungal recovery, is not well documented. This study addressed these gaps using extensive data-based evaluation focused on molds. We identified the best medium types and incubation times for better fungal culture practice. We analyzed 1,821 molds from 1,687 positive specimens in our cohort of approximately 30,000 fungal cultures. Mold recovery peaked between 3 and 7 days of incubation, dependent upon the type of mold. Some well-defined fungal pathogens, such as Histoplasma capsulatum and species, were isolated in the fourth week of incubation. Inhibitory mold agar was identified as the best medium for recovering all mold types among all tested specimen sources. As we are aware, this is the largest study of fungal culture methods and supports 4 weeks of incubation for optimal mold recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/Spectrum.00080-21DOI Listing
September 2021

Improving systems of prenatal and postpartum care for hyperglycemia in pregnancy: A process evaluation.

Int J Gynaecol Obstet 2021 Jul 31. Epub 2021 Jul 31.

Division of Wellbeing and Preventable Chronic Disease, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

Objective: To identify successes to date and opportunities for improvement in the implementation of a complex health systems intervention aiming to improve prenatal and postpartum care and health outcomes for women with hyperglycemia in pregnancy in regional and remote Australia.

Methods: A qualitative evaluation, underpinned by the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance), was conducted mid-intervention. Semi-structured interviews were conducted with the participants, who included clinicians, regional policymakers and managers, and study implementation staff.

Results: Interviewees (n = 45) reported that the early phase of the intervention had resulted in the establishment of a clinician network, increased clinician awareness of hyperglycemia in pregnancy, and improvements in management, including earlier referral for specialist care and a focus on improving communication with women. Enablers of implementation included existing relationships with stakeholders and alignment of the intervention with health service priorities. Challenges included engaging remote clinicians and the labor-intensive nature of maintaining a clinical register of women with hyperglycemia in pregnancy.

Conclusion: The early phase of this health systems intervention has had a positive perceived impact on systems of care for women with hyperglycemia in pregnancy. Findings have informed modifications to the intervention, including the development of a communication and engagement strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.13850DOI Listing
July 2021

Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study.

Lancet Neurol 2021 08;20(8):627-638

Department of Intensive Care Adults, Erasmus MC - University Medical Center, Rotterdam, Netherlands. Electronic address:

Background: Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.

Methods: We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.

Findings: 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1·48 L (IQR 1·12 to 2·09) to 4·23 L (3·78 to 4·94) across centres. The median of the mean daily fluid balance ranged from -0·85 L (IQR -1·51 to -0·49) to 1·13 L (0·99 to 1·37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1·10 [95% CI 1·07 to 1·12] per 0·1 L increase) and worse functional outcome (1·04 [1·02 to 1·05] per 0·1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1·05 [1·03 to 1·06] per 0·1 L increase) and worse functional outcome (1·04 [1·03 to 1·04] per 1-point decrease of the GOSE per 0·1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1·17 [95% CI 1·05 to 1·29]) and worse functional outcome (1·07 [1·02 to 1·13]), but higher fluid input was not associated with ICU mortality (OR 0·95 [0·90 to 1·00]) or worse functional outcome (1·01 [0·98 to 1·03]).

Interpretation: In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome.

Funding: European Commission 7th Framework program and the Australian Health and Medical Research Council.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(21)00162-9DOI Listing
August 2021

Extensive Perivillous Fibrin and Intervillous Histiocytosis in a SARS-CoV-2 Infected Placenta From an Uninfected Newborn: A Case Report Including Immunohistochemical Profiling.

Pediatr Dev Pathol 2021 Jun 28:10935266211025122. Epub 2021 Jun 28.

Department of Pathology, Children's Healthcare of Atlanta, Atlanta, Georgia.

Placental infection by SARS-CoV-2 with various pathologic alterations reported. Inflammatory findings, such as extensive perivillous fibrin deposition and intervillous histiocytosis, have been postulated as risk factors for fetal infection by SARS-CoV-2. We describe the placental findings in a case of a 31-year-old mother with SARS-CoV-2 infection who delivered a preterm female neonate who tested negative for SAR-CoV2 infection. Placental examination demonstrated a small for gestational age placenta with extensive intervillous histiocytosis, syncytiotrophoblast karyorrhexis, and diffuse intervillous fibrin deposition. Immunohistochemical staining demonstrated infection of the syncytiotrophoblasts by SARS-CoV-2 inversely related to the presence of intervillous histiocytes and fibrin deposition. Our case demonstrates that despite extensive placental pathology, no fetal transmission of SARS-CoV-2 occurred, as well as postulates a relationship between placental infection, inflammation, and fibrin deposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10935266211025122DOI Listing
June 2021

Association of Aortic Stiffness With Biomarkers of Neuroinflammation, Synaptic Dysfunction, and Neurodegeneration.

Neurology 2021 07 24;97(4):e329-e340. Epub 2021 May 24.

From the Vanderbilt Memory & Alzheimer's Center (E.E.M., D.L., J.L., S.J.S., F.E.C., K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Department of Biostatistics (D.L.), Radiology & Radiological Sciences (J.G.T., S.N., J.J.C.), Department of Neurology (K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Division of Cardiovascular Medicine (S.P.B., J.A.B., A.L.J.), Department of Medicine, and Vanderbilt Genetics Institute (T.J.H.), Vanderbilt University Medical Center, Nashville, TN; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Molndal, Sweden; Department of Neurodegenerative Disease (H.Z.), University College London Institute of Neurology, Queen Square; and United Kingdom Dementia Research Institute at University College London (H.Z.), UK.

Objectives: To test the hypothesis that increased aortic stiffening is associated with greater CSF evidence of core Alzheimer disease pathology (β-amyloid [Aβ], phosphorylated tau [p-tau]), neurodegeneration (total tau [t-tau]), synaptic dysfunction (neurogranin), neuroaxonal injury (neurofilament light [NFL]), and neuroinflammation (YKL-40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]), we analyzed pulse wave velocity (PWV) data and CSF data among older adults.

Methods: Participants free of stroke and dementia from the Vanderbilt Memory and Aging Project, an observational community-based study, underwent cardiac magnetic resonance to assess aortic PWV (meters per second) and lumbar puncture to obtain CSF. Linear regressions related aortic PWV to CSF Aβ, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations after adjustment for age, race/ethnicity, education, apolipoprotein (APOE) ε4 status, Framingham Stroke Risk Profile, and cognitive diagnosis. Models were repeated testing PWV interactions with age, diagnosis, ε4, and hypertension on each biomarker.

Results: One hundred forty-six participants were examined (age 72 ± 6 years). Aortic PWV interacted with age on p-tau (β = 0.31, = 0.04), t-tau, (β = 2.67, = 0.05), neurogranin (β = 0.94, = 0.04), and sTREM2 (β = 20.4, = 0.05). Among participants >73 years of age, higher aortic PWV related to higher p-tau (β = 2.4, = 0.03), t-tau (β = 19.3, = 0.05), neurogranin (β = 8.4, = 0.01), and YKL-40 concentrations (β = 7,880, = 0.005). Aortic PWV had modest interactions with diagnosis on neurogranin (β = -10.76, = 0.03) and hypertension status on YKL-40 (β = 18,020, < 0.001).

Conclusions: Among our oldest participants, ≥74 years of age, greater aortic stiffening is associated with in vivo biomarker evidence of neuroinflammation, tau phosphorylation, synaptic dysfunction, and neurodegeneration, but not amyloidosis. Central arterial stiffening may lead to cumulative cerebral microcirculatory damage and reduced blood flow delivery to tissue, resulting in neuroinflammation and neurodegeneration in more advanced age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362359PMC
July 2021

Real-world utilisation of ASCT in multiple myeloma (MM): a report from the Australian and New Zealand myeloma and related diseases registry (MRDR).

Bone Marrow Transplant 2021 May 19. Epub 2021 May 19.

Alfred Health-Monash University, Melbourne, VIC, Australia.

Supported by clinical trial proven survival benefit, clinical guidelines recommend upfront autologous stem cell transplantation (ASCT) for eligible MM patients. However, reported real-world utilisation is lower than expected (40-60%). We reviewed ASCT utilisation, demographics and outcomes for MM patients (≤70 years, ≥12-month follow-up) enroled onto the Australian/New Zealand MRDR from June 2012 to May 2020. In 982 patients (<65 years: 684, 65-70 years: 298), ASCT utilisation was 76% overall (<65 years: 83%, 65-70 years: 61%, front-line therapy: 67%). Non-ASCT recipients were older (median age: 65 years vs 60 years, p < 0.001), had more comorbidities (cardiac disease: 16.9% vs 5.4%, p < 0.001; diabetes: 19.1% vs 7.0%, p < 0.001; renal dysfunction: median eGFR(ml/min): 68 vs 80, p < 0.001), inferior performance status (ECOG ≥ 2: 26% vs 13%, p < 0.001) and higher-risk MM (ISS-3: 37% vs 26%, p = 0.009, R-ISS-3 18.6% vs 11.8%, p = 0.051) than ASCT recipients. ASCT survival benefit (median progression-free survival (PFS): 45.3 months vs 35.2 months, p < 0.001; overall survival (OS): NR vs 64.0 months, p < 0.001) was maintained irrespective of age (<65 years: median PFS: 45.3 months vs 37.7 months, p = 0.04, OS: NR vs 68.2 months, p = 0.002; 65-70 years: median PFS: 46.7 months vs 29.2 months, p < 0.001, OS: 76.9 months vs 55.6 months, p = 0.005). This large, real-world cohort reaffirms ASCT survival benefit, including in 'older' patients necessitating well-designed studies evaluating ASCT in 'older' MM to inform evidence-based patient selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-021-01308-8DOI Listing
May 2021

Structural and Functional Imaging of the Retina in Central Retinal Artery Occlusion - Current Approaches and Future Directions.

J Stroke Cerebrovasc Dis 2021 Jul 17;30(7):105828. Epub 2021 May 17.

Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address:

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke which affects the retina. Intravenous thrombolysis is emerging as a compelling therapeutic approach. However, it is not known which patients may benefit from this therapy because there are no imaging modalities that adequately distinguish viable retina from irreversibly infarcted retina. The inner retina receives arterial supply from the central retinal artery and there is robust collateralization between this circulation and the outer retinal circulation, provided by the posterior ciliary circulation. Fundus photography can show canonical changes associated with CRAO including a cherry-red spot, arteriolar boxcarring and retinal pallor. Fluorescein angiography provides 2-dimensional imaging of the retinal circulation and can distinguish a complete from a partial CRAO as well as central versus peripheral retinal non-perfusion. Transorbital ultrasonography may assay flow through the central retinal artery and is useful in the exclusion of other orbital pathology that can mimic CRAO. Optical coherence tomography provides structural information on the different layers of the retina and exploratory work has described its utility in determining the time since onset of ischemia. Two experimental techniques are discussed. 1) Retinal functional imaging permits generation of capillary perfusion maps and can assay retinal oxygenation and blood flow velocity. 2) Photoacoustic imaging combines the principles of optical excitation and ultrasonic detection and - in animal studies - has been used to determine the retinal oxygen metabolic rate. Future techniques to determine retinal viability in clinical practice will require rapid, easily used, and reproducible methods that can be deployed in the emergency setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105828DOI Listing
July 2021

Targeting Cancer Stem Cells with Differentiation Agents as an Alternative to Genotoxic Chemotherapy for the Treatment of Malignant Testicular Germ Cell Tumors.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.

Testicular germ cell tumors (TGCTs) are exceptionally sensitive to genotoxic chemotherapy, resulting in a high cure rate for the young men presenting with these malignancies. However, this treatment is associated with significant toxicity, and a subset of malignant TGCTs demonstrate chemoresistance. Mixed nonseminomas often contain pluripotent embryonal carcinoma (EC) cells, the cancer stem cells (CSCs) of these tumors. We hypothesized that differentiation therapy, a treatment strategy which aims to induce differentiation of tumor-propagating CSCs to slow tumor growth, could effectively treat mixed nonseminomas without significant toxicity. The FDA-approved antipsychotic thioridazine and the agricultural antibiotic salinomycin are two drugs previously found to selectively target CSCs, and here we report that these agents differentiate EC cells in vitro and greatly reduce their tumorigenic potential in vivo. Using a novel transformed induced pluripotent stem cell allograft model and a human xenograft model, we show that thioridazine extends the survival of tumor-bearing mice and can reduce the number of pluripotent EC cells within tumors. These results suggest that thioridazine could be repurposed as an alternative TGCT treatment that avoids the toxicity of conventional chemotherapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122873PMC
April 2021

The Myeloma Landscape in Australia and New Zealand: The First 8 Years of the Myeloma and Related Diseases Registry (MRDR).

Clin Lymphoma Myeloma Leuk 2021 Jun 30;21(6):e510-e520. Epub 2021 Jan 30.

Department of Haematology, Alfred Health-Monash University, Melbourne, Victoria, Australia. Electronic address:

Background: Real-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020.

Methods: We reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS).

Results: As of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001).

Conclusion: Clinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clml.2021.01.016DOI Listing
June 2021

Responses of larvae to heat waves.

J Exp Biol 2021 04 6;224(Pt 7). Epub 2021 Apr 6.

Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

Climate change is increasing the frequency of heat waves and other extreme weather events experienced by organisms. How does the number and developmental timing of heat waves affect survival, growth and development of insects? Do heat waves early in development alter performance later in development? We addressed these questions using experimental heat waves with larvae of the tobacco hornworm, The experiments used diurnally fluctuating temperature treatments differing in the number (0-3) and developmental timing (early, middle and/or late in larval development) of heat waves, in which a single heat wave involved three consecutive days with a daily maximum temperature of 42°C. Survival to pupation declined with increasing number of heat waves. Multiple (but not single) heat waves significantly reduced development time and pupal mass; the best models for the data indicated that both the number and developmental timing of heat waves affected performance. In addition, heat waves earlier in development significantly reduced growth and development rates later in larval development. Our results illustrate how the frequency and developmental timing of sublethal heat waves can have important consequences for life history traits in insects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jeb.236505DOI Listing
April 2021

A New Approach to Assessing Children's Interpretation of Severity Qualifiers in a Multi-Attribute Utility Instrument-The EQ-5D-Y-5L: Development and Testing.

Patient 2021 Sep 2;14(5):591-600. Epub 2021 Mar 2.

The EuroQol Group, Version Management Committee, Rotterdam, Netherlands.

Introduction: The beta EQ-5D-Y-5L is a new patient-reported outcome measure (PROM) for children aged 8-15 years that is currently under development by the EuroQol Group. The EQ-5D-Y-5L is similar to the EQ-5D-Y but has five levels of severity per dimension rather than three. The increased number of levels increases the granularity of the responses but possibly has also increased the difficulty of distinguishing between levels. The EuroQoL's Version Management Committee (VMC) required a robust method to determine how well children distinguish between the five EQ-5D-Y-5L ordinal severity qualifiers (i.e. 'no problems' through to 'extreme problems'), which are a critical aspect of both health measurement and the valuation of health states.

Objective: This paper describes the development, testing, selection, and piloting of such a method.

Methods: Following a literature review and consultation with the wider VMC and a Language Support Services agency, a range of exercises were developed to assess the ordering and comprehension of the five severity qualifiers. Three exercises were pre-tested with children in Spain and New Zealand. One exercise, preferred and understood by children, was then piloted.

Results: Five children in Spain and 11 in New Zealand tested the three exercises. In both countries, all children found the three exercises easy to understand and complete. Of the 12 children who expressed a preference, nine said they preferred the card ranking. Card ranking also allowed the interviewer to observe difficult choices being made as the children physically rearranged the card order until they settled on their final order. Following rigorous assessment of translatability and cultural portability by an independent Language Support Service, card ranking was piloted in South Africa (n = 9) and in Indonesia (n = 10), where it highlighted severity qualifier order inversions that would otherwise not have been detected.

Conclusion: The card ranking exercise was found to be a preferred and acceptable means of testing the ordering of translations of severity qualifiers among children. Additional formal testing of the exercise in other countries and languages is now underway. The approach developed and tested by the VMC for cognitive debriefing of beta EQ-5D-Y-5L language/country versions may also be useful in determining the adequacy of translated qualifiers in debriefing of adult EQ-5D-5L versions and other PROMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40271-021-00496-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357732PMC
September 2021

Impact of Cardiovascular Hemodynamics on Cognitive Aging.

Arterioscler Thromb Vasc Biol 2021 04 11;41(4):1255-1264. Epub 2021 Feb 11.

Vanderbilt Memory & Alzheimer's Center (E.E.M., A.L.J.), Vanderbilt University Medical Center, Nashville, TN.

[Figure: see text].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.311909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990698PMC
April 2021

A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality.

Crit Care Med 2021 04;49(4):e394-e403

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objectives: Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown.

Design: A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use.

Setting: Twenty-nine university-affiliated teaching hospitals in seven countries.

Patients: A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline.

Interventions: None.

Measurements And Main Results: We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death.

Conclusions: In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963441PMC
April 2021

Lipidome-based Targeting of STAT3-driven Breast Cancer Cells Using Poly-l-glutamic Acid-coated Layer-by-Layer Nanoparticles.

Mol Cancer Ther 2021 04 3;20(4):726-738. Epub 2021 Feb 3.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

The oncogenic transcription factor STAT3 is aberrantly activated in 70% of breast cancers, including nearly all triple-negative breast cancers (TNBCs). Because STAT3 is difficult to target directly, we considered whether metabolic changes driven by activated STAT3 could provide a therapeutic opportunity. We found that STAT3 prominently modulated several lipid classes, with most profound effects on N-acyl taurine and arachidonic acid, both of which are involved in plasma membrane remodeling. To exploit these metabolic changes therapeutically, we screened a library of layer-by-layer (LbL) nanoparticles (NPs) differing in the surface layer that modulates interactivity with the cell membrane. We found that poly-l-glutamic acid (PLE)-coated NPs bind to STAT3-transformed breast cancer cells with 50% greater efficiency than to nontransformed cells, and the heightened PLE-NP binding to TNBC cells was attenuated by STAT3 inhibition. This effect was also observed in densely packed three-dimensional breast cancer organoids. As STAT3-transformed cells show greater resistance to cytotoxic agents, we evaluated whether enhanced targeted delivery via PLE-NPs would provide a therapeutic advantage. We found that cisplatin-loaded PLE-NPs induced apoptosis of STAT3-driven cells at lower doses compared with both unencapsulated cisplatin and cisplatin-loaded nontargeted NPs. In addition, because radiation is commonly used in breast cancer treatment, and may alter cellular lipid distribution, we analyzed its effect on PLE-NP-cell binding. Irradiation of cells enhanced the STAT3-targeting properties of PLE-NPs in a dose-dependent manner, suggesting potential synergies between these therapeutic modalities. These findings suggest that cellular lipid changes driven by activated STAT3 may be exploited therapeutically using unique LbL NPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-20-0505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026705PMC
April 2021

Interprofessional Education Week: the impact of active and passive learning activities on students' perceptions of interprofessional education.

J Interprof Care 2021 Sep-Oct;35(5):799-802. Epub 2021 Jan 15.

Department of Athletic Training, University of Indianapolis, Indianapolis, IN, USA.

Healthcare professions faculty at a private Midwestern university designed an Interprofessional Education (IPE) Week, consisting of 12 different interprofessional learning activities over the span of one week. The purpose of the study was to determine students' perceptions toward interprofessional healthcare, as measured by the Student Perceptions of Interprofessional Clinical Education-Revised (SPICE-R), one week before and one week after the events to determine if the type of learning activity - more passive, didactic-type events or active learning events - impacted outcomes. Of the over 400 students representing predominantly athletic training, nursing, occupational therapy, and physical therapy programs who attended IPE Week, a total of 190 health professions students completed the pre- and post-IPE Week SPICE-R. Students who attended an active learning activity had a statistically significant increase in all three factors of the tool (interprofessional teamwork and team-based practice, roles/responsibilities for collaborative practice, and patient outcomes from collaborative practice) while students who attended more passive didactic type events only showed a statistically significant increase in roles/responsibilities and patient outcomes. This study demonstrates the utility of an IPE Week on student perceptions and highlights the potential importance of active interprofessional learning offerings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13561820.2020.1856798DOI Listing
January 2021

Growth, stress, and acclimation responses to fluctuating temperatures in field and domesticated populations of .

Ecol Evol 2020 Dec 11;10(24):13980-13989. Epub 2020 Nov 11.

Department of Biology University of North Carolina Chapel Hill NC USA.

Diurnal fluctuations in temperature are ubiquitous in terrestrial environments, and insects and other ectotherms have evolved to tolerate or acclimate to such fluctuations. Few studies have examined whether ectotherms acclimate to diurnal temperature fluctuations, or how natural and domesticated populations differ in their responses to diurnal fluctuations. We examine how diurnally fluctuating temperatures during development affect growth, acclimation, and stress responses for two populations of : a field population that typically experiences wide variation in mean and fluctuations in temperature, and a laboratory population that has been domesticated in nearly constant temperatures for more than 300 generations. Laboratory experiments showed that diurnal fluctuations throughout larval development reduced pupal mass for the laboratory but not the field population. The differing effects of diurnal fluctuations were greatest at higher mean temperature (30°C): Here diurnal fluctuations reduced pupal mass and increased pupal development time for the laboratory population, but had little effect for the field population. We also evaluated how mean and fluctuations in temperature during early larval development affected growth rate during the final larval instar as a function of test temperature. At an intermediate (25°C) mean temperature, both the laboratory and field population showed a positive acclimation response to diurnal fluctuations, in which subsequent growth rate was significantly higher at most test temperatures. In contrast at higher mean temperature (30°C), diurnal fluctuations significantly reduced subsequent growth rate at most test temperatures for the laboratory population, but not for the field population. These results suggest that during domestication in constant temperatures, the laboratory population has lost the capacity to tolerate or acclimate to high and fluctuating temperatures. Population differences in acclimation capacity in response to temperature fluctuations have not been previously demonstrated, but they may be important for understanding the evolution of reaction norms and performance curves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.6991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771122PMC
December 2020

Beyond housing: Understanding community integration among homeless-experienced veteran families in the United States.

Health Soc Care Community 2020 Dec 19. Epub 2020 Dec 19.

VA Health Service Research & Development (HSR&D) Center for the Study of Healthcare Innovation, Implementation & Policy (CSHIIP), VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Community integration is important to address among homeless-experienced individuals. Little is known about helping veteran families (families with a parent who is a veteran) integrate into the community after homelessness. We sought to understand the experiences of community integration among homeless-experienced veteran families. We used a two-stage, community-partnered approach. First, we analysed 16 interviews with homeless-experienced veteran parents (parents who served in the military; n = 9) living in permanent housing and providers of homeless services (n = 7), conducted from February to September 2016, for themes of community integration. Second, we developed a workgroup of nine homeless-experienced veteran parents living in a permanent housing facility, who met four times from December 2016 to July 2017 to further understand community integration. We audio-recorded, transcribed and analysed the interviews and workgroups for community integration themes. For the analysis, we developed community integration categories based on interactions outside of the household and built a codebook describing each topic. We used the codebook to code the individual interviews and parent workgroup sessions after concluding that the workgroup and interview topics were consistent. Findings were shared with the workgroup. We describe our findings across three stages of community integration: (a) first housed, (b) adjusting to housing and the community, and (c) housing maintenance and community integration. We found that parents tended to isolate after transitioning into permanent housing. After this, families encountered new challenges and were guarded about losing housing. One facilitator to community integration was connecting through children to other parents and community institutions (e.g. schools). Although parents felt safe around other veterans, many felt judged by non-veterans. Parents and providers reported a need for resources and advocacy after obtaining housing. We share implications for improving community integration among homeless-experienced veteran families, including providing resources after obtaining housing, involving schools in facilitating social connections, and combating stigma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hsc.13233DOI Listing
December 2020

Lower Cardiac Output Relates to Longitudinal Cognitive Decline in Aging Adults.

Front Psychol 2020 9;11:569355. Epub 2020 Nov 9.

Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.

Background: Subclinical reductions in cardiac output correspond to lower cerebral blood flow (CBF), placing the brain at risk for functional changes.

Objectives: This study aims to establish the consequences of reduced cardiac output on longitudinal cognitive outcomes in aging adults.

Methods: Vanderbilt Memory and Aging Project participants free of clinical dementia and heart failure ( = 306, 73 ± 7, 58% male) underwent baseline echocardiography to assess cardiac output (L/min) and longitudinal neuropsychological assessment at baseline, 18 months, 3 and 5 years. Linear mixed-effects regressions related cardiac output to trajectory for each longitudinal neuropsychological outcome, adjusting for age, sex, race/ethnicity, education, body surface area, Framingham Stroke Risk Profile score, apolipoprotein E () ε4 status and follow-up time. Models were repeated, testing interactions with cognitive diagnosis and ε4 status.

Results: Lower baseline cardiac output related to faster declines in language (β = 0.11, = 0.01), information processing speed (β = 0.31, = 0.006), visuospatial skills (β = 0.09, = 0.03), and episodic memory (β = 0.02, = 0.001). No interactions were observed ( > 0.26). -ε4 status modified the association between cardiac output and longitudinal episodic memory (β = 0.03, = 0.047) and information processing speed outcomes (β = 0.55, = 0.02) with associations stronger in ε4 carriers.

Conclusion: The present study provides evidence that even subtle reductions in cardiac output may be associated with more adverse longitudinal cognitive health, including worse language, information processing speed, visuospatial skills, and episodic memory performances. Preservation of healthy cardiac functioning is important for maintaining optimal brain aging among older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2020.569355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680861PMC
November 2020

Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment.

Brain Imaging Behav 2021 Aug 10;15(4):2040-2050. Epub 2020 Oct 10.

Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA.

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T and white matter hyperintensities assessed on T-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-020-00398-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035362PMC
August 2021

Dutch translation and linguistic validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™).

J Patient Rep Outcomes 2020 Oct 6;4(1):81. Epub 2020 Oct 6.

Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Background: The U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) is a library of items for assessing symptomatic adverse events by patient self-report in oncology trials. The aim of this multi-site study was to generate and linguistically validate a Dutch language version of the U.S. PRO-CTCAE for use in the Netherlands and Dutch-speaking Belgium.

Methods: All 124 items in the PRO-CTCAE item library were translated into Dutch using established translation procedures, including dual forward translations, reconciliation, back-translation, reconciliation of the source with the back-translation, and expert reviews. Harmonization of the translation for use in both the Netherlands and Belgium was achieved via an iterative review process in which the translations were discussed and reconciled by consensus of PRO experts, clinicians and bilingual Dutch translators. The translated PRO-CTCAE™ items were completed by a geographically-diverse sample of Dutch speaking patients from the Netherlands (n = 40) and Belgium (n = 60), and who were currently receiving or who had recently completed cancer-directed therapy. Patients were diverse with respect to age, sex, educational attainment, and cancer diagnosis. Cognitive debriefing, using a semi-structured interview guide, probed for comprehension and clarity of PRO-CTCAE symptom terms, attributes (e.g. frequency, severity, interference), response choices, and understanding of 'at its worst' and 'in the last 7 days'. Items for which the patient data indicated possible difficulties were considered for revision.

Results: Three items underwent minor phrasing revision and retesting was not deemed necessary. The symptom term for stretch marks was poorly understood by 12.5% of participants, and this item was revised to include parenthetical phrasing. It was retested with 10 participants from Belgium (n = 5) and the Netherlands (n = 5) and demonstrated acceptable comprehension.

Conclusions: The Dutch language version of PRO-CTCAE has been successfully developed and linguistically validated for use in oncology studies in the Netherlands and Dutch-speaking Belgium. Extending the availability of NCI PRO-CTCAE in languages beyond English increases international consistency in the capture of Patient-Reported outcomes in patients participating in cancer clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41687-020-00249-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538479PMC
October 2020

Mental Health Community and Health System Issues in COVID-19: Lessons from Academic, Community, Provider and Policy Stakeholders.

Ethn Dis 2020 24;30(4):695-700. Epub 2020 Sep 24.

Resnick Neuropsychiatric Hospital and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA.

The coronavirus pandemic of 2019 (COVID-19) has created unprecedented changes to everyday life for millions of Americans due to job loss, school closures, stay-at-home orders and health and mortality consequences. In turn, physicians, academics, and policymakers have turned their attention to the public mental health toll of COVID-19. This commentary reporting from the field integrates perceptions of academic, community, health system, and policy leaders from state, county, and local levels in commenting on community mental health needs in the COVID-19 pandemic. Stakeholders noted the broad public health scope of mental health challenges while expressing concern about exacerbation of existing disparities in access and adverse social determinants, including for communities with high COVID-19 infection rates, such as African Americans and Latinos. They noted rapid changes toward telehealth and remote care, and the importance of understanding impacts of changes, including who may benefit or have limited access, with implications for future services delivery. Needs for expanded workforce and training in mental health were noted, as well as potential public health value of expanding digital resources tailored to local populations for enhancing resilience to stressors. The COVID-19 pandemic has led to changes in delivery of health care services across populations and systems. Concerns over the mental health impact of COVID-19 has enhanced interest in remote mental care delivery and preventive services, while being mindful of potential for enhanced disparities and needs to address social determinants of health. Ongoing quality improvement across systems can integrate lessons learned to enhance a public mental well-being.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18865/ed.30.4.695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518533PMC
October 2020

Effect of aspirin on deaths associated with sepsis in healthy older people (ANTISEPSIS): a randomised, double-blind, placebo-controlled primary prevention trial.

Lancet Respir Med 2021 02 17;9(2):186-195. Epub 2020 Sep 17.

Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, QLD, Australia.

Background: Sepsis is a serious global health issue and a major cause of death and disability. The availability of a simple, community-based preventive strategy could substantially reduce the burden of sepsis. We aimed to establish whether low-dose aspirin reduced deaths or hospital admissions associated with sepsis in older people.

Methods: ANTISEPSIS was a substudy of ASPREE (a randomised controlled primary prevention trial of low-dose aspirin [100 mg per day] compared with placebo in community dwelling older adults conducted in Australia and the USA), with the Australian cohort included in the ANTISEPSIS substudy. Inclusion criteria were participants aged at least 70 years who did not have major illnesses. Participants were block randomised (1:1) via a centralised web portal and stratified by general practice and age. Participants, investigators, and staff were masked to the intervention. Teams of clinical specialist investigators assessed potential sepsis events to establish if they satisfied the primary endpoint of death associated with sepsis. The analyses were by intention-to-treat with univariate survival analysis methods, the log-rank test, and Cox proportional hazards regression. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000349741.

Results: Between March 10, 2010, and Dec 24, 2014, of 20 288 individuals assessed for eligibility, 16 703 participants aged 70 years and older at trial entry were enrolled and followed up for a median of 4·6 years (IQR 3·6-5·6). 8322 (49·8%) participants were assigned to receive aspirin and 8381 (50·2%) to placebo. 203 deaths were considered to be associated with sepsis. Univariate analysis showed similar rates of death associated with sepsis in the two study groups (hazard ratio for aspirin vs placebo 1·08, 95% CI 0·82-1·43; p=0·57). Adverse events were previously reported in the ASPREE trial.

Interpretation: Daily low-dose aspirin treatment did not reduce deaths associated with sepsis in community dwelling older adults. Our findings do not support the use of aspirin as a primary prevention strategy to reduce the burden of sepsis in this population.

Funding: National Health and Medical Research Council of Australia, National Institutes of Health, Monash University.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(20)30411-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957956PMC
February 2021

Unpalatable food for thought: Let marketing research guide effective public obesity interventions.

Obes Rev 2021 02 9;22(2):e13141. Epub 2020 Sep 9.

Grenoble Ecole de Management, Grenoble, France & IREGE, Université Savoie Mont Blanc, Chambery, France.

The prevalence of obesity is growing unabatedly despite the considerable efforts directed at the problem. Although abundant research has contributed to our understanding of the multifactorial causes of obesity, there is less attention to research that is relevant for guiding social marketers, public health professionals and policymakers in delivering public health interventions for countering and/or preventing the problem of obesity. This review offers six points for identifying and developing research relevant for guiding community-wide obesity interventions based on the idea that an applied marketing research perspective offers a better model for identifying effective interventions than more theoretical academic research. Specifically, the research guiding public health and social marketing interventions needs to (1) provide information on ultimate outcomes (weight, health and unintended consequences) more than intermediate outcomes (beliefs, attitudes and behaviour), (2) report on observations collected over the longer term, (3) use natural settings (even at a cost of internal validity), (4) endeavour to overcome observer-effects, (5) report effect sizes (rather than statistical significance) and (6) use moderator analyses to capture variation in how a population responds to interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/obr.13141DOI Listing
February 2021

Assessing reliability and validity of a functional outcome measure for adolescents with hypermobility spectrum disorder.

Disabil Rehabil 2020 Jul 10:1-6. Epub 2020 Jul 10.

College of Health Science and School of Nursing, University of Indianapolis, Indianapolis, IN, USA.

Purpose: To determine the reliability and validity of the upper extremity function and pain scales of the Pediatric Outcomes Data Collecton Instrument (PODCI UEF and PODCI P) as an outcome measure in adolescents with Hypermobility Spectrum Disorder (HSDs).

Materials And Methods: An observational study using a cross-section design was conducted. A convenience sample of 83 adolescents (age 11-18 years) with HSDs were recruited. Test-retest reliability of the PODCI UEF and PODCI P was examined using Lin's concordance correlation coefficient (ρ). Concurrent validity was established by comparing the PODCI UEF to the PROMIS Pediatric Upper Extremity-Short Form (PROMIS PUE-SF) and comparing the PODCI P to Numeric Rating Scale (NRS) using Spearman rho correlations.

Results: There was high test-retest reliability for the PODCI UEF, = 0.81 ( < 0.001) and moderate test-retest reliability for the PODCI P, = 0.68 ( < 0.001). There was a strong correlation between the PODCI UEF and the PROMIS PUE-SF, = 0.80 ( < 0.001) and a moderate inverse relationship = -0.73 ( < 0.001) between PODCI P and NRS scores ( = 150).

Conclusion: The PODCI UEF and PODCI P may be a valid and reliable outcome measure in adolescents with HSDs.Implications for rehabilitationAdolescents with joint hypermobility can have chronic pain, fatigue, and decreased participation in daily activities.Clinical use of valid and reliable outcome measures to measure change may assist in planning care and identifying best practice for the management of HSDs.The PODCI was designed to be used as an outcome measure for chronic musculoskeletal conditions and has demonstrated test-retest reliability, validity, and responsiveness to change in other pediatric populations.The PODCI may be a valid and reliable outcome measure in adolescents with HSDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09638288.2020.1788177DOI Listing
July 2020

Mild Cognitive Impairment Staging Yields Genetic Susceptibility, Biomarker, and Neuroimaging Differences.

Front Aging Neurosci 2020 5;12:139. Epub 2020 Jun 5.

Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.

Introduction: While Alzheimer's disease (AD) is divided into severity stages, mild cognitive impairment (MCI) remains a solitary construct despite clinical and prognostic heterogeneity. This study aimed to characterize differences in genetic, cerebrospinal fluid (CSF), neuroimaging, and neuropsychological markers across clinician-derived MCI stages.

Methods: Vanderbilt Memory & Aging Project participants with MCI were categorized into 3 severity subtypes at screening based on neuropsychological assessment, functional assessment, and Clinical Dementia Rating interview, including mild ( = 18, 75 ± 8 years), moderate ( = 89 72 ± 7 years), and severe subtypes ( = 18, 78 ± 8 years). At enrollment, participants underwent neuropsychological testing, 3T brain magnetic resonance imaging (MRI), and optional fasting lumbar puncture to obtain CSF. Neuropsychological testing and MRI were repeated at 18-months, 3-years, and 5-years with a mean follow-up time of 3.3 years. Ordinary least square regressions examined cross-sectional associations between MCI severity and apolipoprotein E ()-ε4 status, CSF biomarkers of amyloid beta (Aβ), phosphorylated tau, total tau, and synaptic dysfunction (neurogranin), baseline neuroimaging biomarkers, and baseline neuropsychological performance. Longitudinal associations between baseline MCI severity and neuroimaging and neuropsychological trajectory were assessed using linear mixed effects models with random intercepts and slopes and a follow-up time interaction. Analyses adjusted for baseline age, sex, race/ethnicity, education, and intracranial volume for MRI models.

Results: Stages differed at baseline on -ε4 status (early < middle = late; -values < 0.03) and CSF Aβ (early > middle = late), phosphorylated and total tau (early = middle < late; -values < 0.05), and neurogranin concentrations (early = middle < late; -values < 0.05). MCI stage related to greater longitudinal cognitive decline, hippocampal atrophy, and inferior lateral ventricle dilation (early < late; -values < 0.03).

Discussion: Clinician staging of MCI severity yielded longitudinal cognitive trajectory and structural neuroimaging differences in regions susceptible to AD neuropathology and neurodegeneration. As expected, participants with more severe MCI symptoms at study entry had greater cognitive decline and gray matter atrophy over time. Differences are likely attributable to baseline differences in amyloidosis, tau, and synaptic dysfunction. MCI staging may provide insight into underlying pathology, prognosis, and therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289958PMC
June 2020
-->