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Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
As rates of obesity, diabetes, and related comorbidities have increased, the consumption of artificial sweeteners (ASs) as sugar substitutes has also risen in popularity as they are perceived as a healthier alternative to sugar sweetened products. However, there is conflicting evidence regarding the impact of AS intake on metabolic and reproductive health. Glucose intolerance during pregnancy due to intake of sugar sweetened foods can result in an increased risk for the development of type 2 diabetes post-pregnancy. However, limited information exists on the impact of AS intake during pregnancy and lactation on the mother’s health in later life. We hypothesised both AS and fructose would impair metabolic health post-partum (PP) following maternal consumption during pregnancy and lactation. Female C57Bl/6 mice received a standard control diet ad libitum with either water (CD), fructose (Fr; 34.7 mm intake), or AS (AS;12.5 mm Acesulfame-K) throughout pregnancy and lactation. Post-weaning, AS and Fr dams were fed the CD diet for the remainder of the experiment. Oral glucose tolerance tests were undertaken 8 weeks PP and dams were humanely killed at 9 weeks PP, with adipose tissue and ovaries collected for analysis. Experimental diets did not influence maternal bodyweight. At 8 weeks PP, increased glucose intolerance was evident in both AS and Fr dams. Adipocyte size was significantly increased in both the AS and Fr groups PP. Further, in the ovary, AS increased expression of genes associated with follicular development and ovulation. Therefore, ASs may not represent beneficial substitutes to fructose during pregnancy, with the potential to increase the risk of T2DM in later life in mothers.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
To evaluate the role of procalcitonin (PCT) results in antibiotic decisions for COVID-19 patients at hospital presentation.
Design, setting, and participants:
Multicenter retrospective observational study of patients ≥18 years hospitalized due to COVID-19 at the Johns Hopkins Health system. Patients who were transferred from another facility with >24 hours stay and patients who died within 48 hours of hospitalization were excluded.
Elevated PCT values were determined based on each hospital’s definition. Antibiotic therapy and PCT results were evaluated for patients with no evidence of bacterial community-acquired pneumonia (bCAP) and patients with confirmed, probable, or possible bCAP. The added value of PCT testing to clinical criteria in detecting bCAP was evaluated using receiving operating curve characteristics (ROC).
Of 962 patients, 611 (64%) received a PCT test. ROC curves for clinical criteria and clinical criteria plus PCT test were similar (at 0.5 ng/mL and 0.25 ng/mL). By bCAP group, median initial PCT values were 0.58 ng/mL (interquartile range [IQR], 0.24–1.14), 0.23 ng/mL (IQR, 0.1–0.63), and 0.15 ng/mL (IQR, 0.09–0.35) for proven/probable, possible, and no bCAP groups, respectively. Among patients without bCAP, an elevated PCT level was associated with 1.8 additional days of CAP therapy (95% CI, 1.01–2.75; P < .01) compared to patients with a negative PCT result after adjusting for potential confounders. Duration of CAP therapy was similar between patients without a PCT test ordered and a low PCT level for no bCAP and possible bCAP groups.
PCT results may be abnormal in COVID-19 patients without bCAP and may result in receipt of unnecessary antibiotics.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.
To identify clinical variables that influence blood culture volume recovery
Retrospective chart review and linear model analysis
A 621-bed Academic Medical Center with a Clinical Laboratory that processes 20,000+ blood cultures annually and dedicated phlebotomy staff for venipuncture
Consecutive patients requiring blood culture
Over a 6-day period, blood volume was determined in 568 culture bottles from 128 unique adult patients, and clinical data from the time of phlebotomy were extracted from hospital electronic medical records. Conditional hierarchical linear models with random effects for patient and phlebotomy occasion were utilized to analyze correlations between values collected from the same patient and during the same phlebotomy occasion.
Blood samples obtained from a central venous catheter yielded, on average, 2.53 mL more blood (95% CI, 1.63–3.44 mL; P<.001) than those from peripheral venipuncture, and aerobic bottles contained 0.38 mL more blood (95% CI, 0.1–0.67 mL; P=.009) than the anaerobic bottles. The remaining clinical variables (eg, hospital department, patient age, body mass index, gender, mean arterial pressure, concomitant systemic antibiotic use, and Charlson comorbidity index score) failed to reach statistical significance (P<.05) in relation to volume.
Blood cultures obtained from central venous catheters contain significantly greater volume than those obtained via peripheral venipuncture. These data highlight the clinically significant issue of low culture volume recovery, indicate that diagnostic and prognostic tools that rely on volume-dependent phenomena (ie, time to positivity) may require further validation under usual clinical practice circumstances, and suggest goals for future institutional performance improvement.
The prospect of improving “noncognitive” skills through intervention increases the need to understand how to represent them in evaluations. Economic assessment of such efforts rarely incorporates these factors, especially when a benefit-cost approach is employed. Programs targeting such skills are more likely to be assessed through approaches that do not monetize noncognitive ability (e.g., using cost-effectiveness analysis). This could lead to ineffective policy formulations in situations where policy is swayed toward programs that can show monetized effects. Benefit-cost analyses (BCAs) that are employed for programs that target noncognitive competencies currently may underestimate the true economic impact if such skills are left out of the equation. The limitations in valuing these skills impede thorough economic assessment for important and effective programs that target noncognitive competencies. This is especially the case for programs for younger children where readily monetized outcomes are few. The targeted outcomes in programs for children are often noncognitive skills, skills that are perceived as vital to healthy human development and valued by parents, teachers, and educators.
In this paper, we review the state of valuation of key noncognitive skills that are often targeted in social policy intervention directed toward children in youth. We examine the state of valuation of noncognitive skills through a summary of the frameworks in research for characterizing noncognitive ability and by considering the measurement approaches for noncognitive skills in terms of origin (interpersonal versus intrapersonal) and measurement type (observed versus assessed). We review examples of recent BCAs that have employed shadow prices for certain noncognitive skills. Finally, we consider what research is necessary to facilitate valuation in BCA in the future. Shadow price methodology should be carried out in a rigorous manner that recognizes uncertainty in cost projections. Improved methodologies in this area will increase the potential for more comprehensive BCA in evaluations of programs for children and youth.
The Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project will test the overarching hypothesis that an active hydrological system exists beneath a West Antarctic ice stream that exerts a major control on ice dynamics, and the metabolic and phylogenetic diversity of the microbial community in subglacial water and sediment. WISSARD will explore Subglacial Lake Whillans (SLW, unofficial name) and its outflow toward the grounding line where it is thought to enter the Ross Ice Shelf seawater cavity. Introducing microbial contamination to the subglacial environment during drilling operations could compromise environmental stewardship and the science objectives of the project, consequently we developed a set of tools and procedures to directly address these issues. WISSARD hot water drilling efforts will include a custom water treatment system designed to remove micron and sub-micron sized particles (biotic and abiotic), irradiate the drilling water with germicidal ultraviolet (UV) radiation, and pasteurize the water to reduce the viability of persisting microbial contamination. Our clean access protocols also include methods to reduce microbial contamination on the surfaces of cables/hoses and down-borehole equipment using germicidal UV exposure and chemical disinfection. This paper presents experimental data showing that our protocols will meet expectations established by international agreement between participating Antarctic nations.
Field tests, using bolts of American elm trees either uninfested or infested with laboratory-reared or feral Hylurgopinus rufipes (Eichhoff), the native elm bark beetle, were conducted to evaluate colonization behavior of the beetle. The data confirm that (1) colonization of elm by H. rufipes can be accounted for by host attractants alone; (2) overwintered adult H. rufipes are attracted to broodwood (moribund or recently cut elm) in the spring, but summer-emergent adults are attracted to healthy elm; and (3) H. rufipes attacks broodwood primarily during evening beetle flights, and females initiate the gallery. A beetle-produced sex pheromone may be involved in the male–female pairing on broodwood.