An embodied conversational agent can serve as a relational agent and provide information, motivation, and behavioral skills. To evaluate the feasibility, acceptability, and preliminary efficacy of My ...Personal Health Guide, a theory-based mobile-delivered embodied conversational agent intervention to improve adherence to antiretroviral therapy in young African American men who have sex with men, we conducted this prospective pilot study using a 3-month pre–post design. Outcome measures included adherence, acceptability, feasibility, pre versus post health literacy, and pre versus post self-efficacy. There were 43 participants. Pill count adherence > 80% improved from 62% at baseline to 88% at follow-up (p = .05). The acceptability of the app was high. Feasibility issues identified included loss of usage data from unplanned participant app deletion. Health literacy improved whereas self-efficacy was high at baseline and follow-up. This pilot study of My Personal Health Guide demonstrated acceptability and preliminary efficacy in improving adherence in this important population.
Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy ...proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort.
A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses.
Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.
Reservoirs of HIV maintained in anatomic compartments during antiretroviral therapy prevent HIV eradication. However, mechanisms driving their persistence and interventions to control them remain ...elusive. Here we report the presence of an inducible HIV reservoir within antigen-specific CD4
T cells in the central nervous system of a 59-year-old male with progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS). HIV production during PML-IRIS was suppressed by modulating inflammation with corticosteroids; selection of HIV drug resistance caused subsequent breakthrough viremia. Therefore, inflammation can influence the composition, distribution and induction of HIV reservoirs, warranting it as a key consideration for developing effective HIV remission strategies.
Deregulation of cap-dependent translation is associated with cancer initiation and progression. The rate-limiting step of protein synthesis is the loading of ribosomes onto mRNA templates stimulated ...by the heterotrimeric complex, eukaryotic initiation factor (eIF)4F. This step represents an attractive target for anticancer drug discovery because it resides at the nexus of the TOR signaling pathway. We have undertaken an ultra-high-throughput screen to identify inhibitors that prevent assembly of the eIF4F complex. One of the identified compounds blocks interaction between two subunits of eIF4F. As a consequence, cap-dependent translation is inhibited. This compound can reverse tumor chemoresistance in a genetically engineered lymphoma mouse model by sensitizing cells to the proapoptotic action of DNA damage. Molecular modeling experiments provide insight into the mechanism of action of this small molecule inhibitor. Our experiments validate targeting the eIF4F complex as a strategy for cancer therapy to modulate chemosensitivity.
Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, ...including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.
Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25OHD) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, ...malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain.
To develop clinical guidelines for the use of vitamin D (cholecalciferol vitamin D3 or ergocalciferol vitamin D2) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing.
A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25OHD testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D.
The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity.
The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.
STUDY DESIGN.A retrospective analysis of patient hospitalization and discharge records.
OBJECTIVE.To examine the association between race and inpatient postoperative complications following lumbar ...spinal fusion surgery.
SUMMARY OF BACKGROUND DATA.Racial disparities in healthcare have been demonstrated across a range of surgical procedures. Previous research has identified race as a social determinant of health that impacts outcomes after lumbar spinal fusion surgery. However, these studies are limited in that they are outdated, contain data from a single institution, analyze small limited samples, and report limited outcomes. Our study aims to expand and update the literature examining the association between race and inpatient postoperative complications following lumbar spine surgery.
METHODS.We analyzed 267,976 patient discharge records for inpatient lumbar spine surgery using data from the Healthcare Cost and Utilization Projectʼs State Inpatient Databases for California, Florida, New York, Maryland, and Kentucky from 2007 through 2014. We used unadjusted bivariate analysis, adjusted multivariable, and stratified analysis to compare patient demographics, present-on-admission comorbidities, hospital characteristics, and complications by categories of race/ethnicity.
RESULTS.Black patients were 8% and 14% more likely than white patients to experience spine surgery specific complications (adjusted odds ratios aOR1.08, 95% confidence interval CI1.03–1.13) and general postoperative complications (aOR1.14, 95% CI1.07–1.20), respectively. Black patients, compared with white patients, also had increased adjusted odds of 30-day readmissions (aOR1.13, 95% CI1.07–1.20), 90-day readmissions (aOR1.07, 95% CI1.02–1.13), longer length of stay (LOS) (adjusted Incidence Rate Ratio1.15, 95% CI1.14–1.16), and higher total charges (adjusted Incidence Rate Ratio1.08, 95% CI1.07–1.09).
CONCLUSION.Our findings demonstrate that black patients, as compared with white patients, are more likely to have postoperative complications, longer postoperative lengths of stay, higher total hospital charges, and increased odds of 30- and 90-day readmissions following lumbar spinal fusion surgery.Level of Evidence4
Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, ...and may increase treatment effect sizes in depression treatment trials.
We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.
We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) as the outcome measure. Exploratory and confirmatory factor analytic approaches will be used to determine pre-treatment (baseline) and post-treatment models of depression, in terms of the number of factors and weighted scores of each item. Differences in the derived factor scores between baseline and outcome measurements will yield an effect size for factor-informed depression change. The difference between the factor-informed effect size and each original trial effect size, calculated with total HRSD-17 scores, will be determined, and the differences modelled with meta-analytic approaches. Risk differences for proportions of patients who achieved remission will also be evaluated. Furthermore, measurement invariance methods will be used to assess potential gender differences.
Our approach will determine whether adopting advanced psychometric analyses can improve precision and better estimate effect sizes in antidepressant treatment trials. The proposed methods could have implications for future trials and other types of studies that use patient-reported outcome measures.
One often observes small but measurable differences in the diffraction data measured from different crystals of a single protein. These differences might reflect structural differences in the protein ...and may reveal the natural dynamism of the molecule in solution. Partitioning these mixed‐state data into single‐state clusters is a critical step that could extract information about the dynamic behavior of proteins from hundreds or thousands of single‐crystal data sets. Mixed‐state data can be obtained deliberately (through intentional perturbation) or inadvertently (while attempting to measure highly redundant single‐crystal data). To the extent that different states adopt different molecular structures, one expects to observe differences in the crystals; each of the polystates will create a polymorph of the crystals. After mixed‐state diffraction data have been measured, deliberately or inadvertently, the challenge is to sort the data into clusters that may represent relevant biological polystates. Here, this problem is addressed using a simple multi‐factor clustering approach that classifies each data set using independent observables, thereby assigning each data set to the correct location in conformational space. This procedure is illustrated using two independent observables, unit‐cell parameters and intensities, to cluster mixed‐state data from chymotrypsinogen (ChTg) crystals. It is observed that the data populate an arc of the reaction trajectory as ChTg is converted into chymotrypsin.
The dynamics of proteins can be explored from polymorphs observed by the clustering of multiple data wedges.
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