Incidence and Outcomes Associated With Clostridium difficile Infections: A Systematic Review and Meta-analysis

Importance: An understanding of the incidence and outcomes of Clostridium difficile infection (CDI) in the United States can inform investments in prevention and treatment interventions. Objective: To quantify the incidence of CDI and its associated hospital length of stay (LOS) in the United States using a systematic literature review and meta-analysis. Data Sources: MEDLINE via Ovid, Cochrane Library Databases via Wiley, Cumulative Index of Nursing and Allied Health Complete via EBSCO Information Services, Scopus, and Web of Science were searched for studies published in the United States between 2000 and 2019 that evaluated CDI and its associated LOS. Study Selection: Incidence data were collected only from multicenter studies that had at least 5 sites. The LOS studies were included only if they assessed postinfection LOS or used methods accounting for time to infection using a multistate model or compared propensity score-matched patients with CDI with control patients without CDI. Long-term-care facility studies were excluded. Of the 119 full-text articles, 86 studies (72.3%) met the selection criteria. Data Extraction and Synthesis: Two independent reviewers performed the data abstraction and quality assessment. Incidence data were pooled only when the denominators used the same units (eg, patient-days). These data were pooled by summing the number of hospital-onset CDI incident cases and the denominators across studies. Random-effects models were used to obtain pooled mean differences. Heterogeneity was assessed using the I2 value. Data analysis was performed in February 2019. Main Outcomes and Measures: Incidence of CDI and CDI-associated hospital LOS in the United States. Results: When the 13 studies that evaluated incidence data in patient-days due to hospital-onset CDI were pooled, the CDI incidence rate was 8.3 cases per 10 000 patient-days. Among propensity score-matched studies (16 of 20 studies), the CDI-associated mean difference in LOS (in days) between patients with and without CDI varied from 3.0 days (95% CI, 1.44-4.63 days) to 21.6 days (95% CI, 19.29-23.90 days). Conclusions and Relevance: Pooled estimates from currently available literature suggest that CDI is associated with a large burden on the health care system. However, these estimates should be interpreted with caution because higher-quality studies should be completed to guide future evaluations of CDI prevention and treatment interventions

Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer

AbstractAdipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism. Glutamine secretion was measured with a bioanalyzer. Western blotting was used to study the effect of PanIN and PDAC cells on expression of glutamine-related enzymes in adipocytes. Adipocytes promote proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient-poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell proliferation in the absence of glutamine, an effect that was glutamine synthetase-dependent and involved PDAC cell-induced down-regulation of glutaminase expression in adipocytes. These findings suggest glutamine transfer as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell proliferation

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Cutaneous Burn Injury Modulates Urinary Antimicrobial Peptide Responses and the Urinary Microbiome

OBJECTIVES: Characterization of urinary bacterial microbiome and antimicrobial peptides after burn injury to identify potential mechanisms leading to urinary tract infections and associated morbidities in burn patients. DESIGN: Retrospective cohort study using human urine from control and burn subjects. SETTING: University research laboratory. PATIENTS: Burn patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from "healthy" volunteers. The urinary bacterial microbiome and antimicrobial peptide levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients versus controls, which positively correlated with a larger percent burn and with the development of urinary tract infection and sepsis postadmission, regardless of age or gender. Urinary psoriasin and β-defensin antimicrobial peptide levels were significantly reduced in burn patients at 1 and 40 hours postadmission. We observed a shift in antimicrobial peptide hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis urinary tract infection isolates. Furthermore, the antimicrobial peptide activity in burn patients was more effective against E. coli than E. faecalis. Urinary tract infection-positive burn patients with altered urinary antimicrobial peptide activity developed either an E. faecalis or Pseudomonas aeruginosa urinary tract infection, suggesting a role for urinary antimicrobial peptides in susceptibility to select uropathogens. CONCLUSIONS: Our data reveal potential links for urinary tract infection development and several morbidities in burn patients through alterations in the urinary microbiome and antimicrobial peptides. Overall, this study supports the concept that early assessment of urinary antimicrobial peptide responses and the bacterial microbiome may be used to predict susceptibility to urinary tract infections and sepsis in burn patients

Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem.

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids

Molecular Epidemiology of Early and Acute HIV Type 1 Infections in the United States Navy and Marine Corps, 2005–2010

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and calculate the most recent common ancestor for the related sequences. We identified 39 individuals infected with subtype B and one infected with CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences and reference sequences in the env and pro/rt regions showed that five samples were part of molecular clusters, a group of two and a group of three, confirmed by single genome amplification. Real-time molecular monitoring of new HIV-1 acquisitions in the Sea Services may have a role in facilitating public health interventions at sites where related HIV-1 infections are identified

Conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities: a scoping review

Introduction: To examine the scope of existing literature on the conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities. Methods: A protocol was developed based on the Joanna Briggs Institute (JBI) scoping review method. MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and EBSCOhost CINAHL, were searched. Results: Eight studies were selected for inclusion; four used quantitative methodology, and four used qualitative methods. Compassion was not defined a priori or a posteriori in any of the included studies. The concept of self-compassion was explicitly defined only for parents of youth with childhood-onset disabilities in three studies a priori. The most reported outcome measure was self-compassion in parents of youth with childhood-onset disabilities. Self-compassion among parents was associated with greater quality of life and resiliency and lower stress, depression, shame and guilt. Discussion: There is limited evidence on the conceptualization, use, and outcomes associated with compassion among youth with childhood-onset disabilities. Self-compassion may be an effective internal coping process among parents of youth with childhood-onset disabilities. Further research is required to understand the meaning of compassion to youth with childhood-onset disabilities, their parents and caregivers. Systematic review registration: https://doi.org/10.17605/OSF.IO/2GRB4

Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study

Objectives: Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case-control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case-control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU. Methods: We identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU). Results: Twelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively). Conclusions: Mixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic

Climate challenges, vulnerabilities, and food security

This paper identifies rare climate challenges in the long-term history of seven areas, three in the subpolar North Atlantic Islands and four in the arid-to-semiarid deserts of the US Southwest. For each case, the vulnerability to food shortage before the climate challenge is quantified based on eight variables encompassing both environmental and social domains. These data are used to evaluate the relationship between the “weight” of vulnerability before a climate challenge and the nature of social change and food security following a challenge. The outcome of this work is directly applicable to debates about disaster management policy