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OBJECTIVES/GOALS: This presentation outlines a novel approach to evaluating multiple risk factors for the development of dose-limiting toxicities in adolescents and young adults with cancer. This is the first to evaluate biobehavioral predictors originally identified in animal models in clinical human studies. METHODS/STUDY POPULATION: Adolescents and young adults (AYAs) have seen the slowest improvements in cancer survival and have some of the highest rates of dose-limiting mucositis (mouth sores). AYAs receiving chemotherapy with a significant chance of dose-limiting mucositis were recruited for a prospective study. Baseline perceived psychologic stress levels and inflammatory markers were collected at the time of chemotherapy administration and participants completed a daily assessment of mucositis for 14 days following chemotherapy. Logistic regression will be used to evaluate stress and inflammation as predictors of mucositis and Sobels testing will evaluate the role of inflammation as mediators in this relationship. RESULTS/ANTICIPATED RESULTS: We anticipate that, as seen in animal models, stress and inflammation will predict mucositis development. First, we hypothesize that stress levels and inflammatory markers will have a direct correlation and that the level of inflammation at the time of chemotherapy administration will predict mucositis incidence and severity. Through mediation testing, we hypothesize that inflammatory markers will explain a significant amount of the variance in mucositis also explained by stress, identifying inflammation as a mediator in this relationship. In all, we expect that stress and inflammation both predict mucositis development and will be identified as important modifiable factors that can be altered to reduce the risk of toxicity development during cancer therapy. DISCUSSION/SIGNIFICANCE: This work intends to evaluate predictors of chemotherapy-related toxicity development in AYAs with cancer and identify areas of intervention that will reduce toxicity profiles and close the gap in cancer survival for AYAs. Findings are applicable to biomedical, nursing, and psychosocial professionals and will inform future, large clinical studies
To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs) reported from 128 acute-care and 132 long-term care Veterans Affairs (VA) facilities.
We compared central-line–associated bloodstream infections (CLABSIs), ventilator-associated events (VAEs), catheter-associated urinary tract infections (CAUTIs), methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile infections and rates reported from each facility monthly to a centralized database before the pandemic (February 2019 through January 2020) and during the pandemic (July 2020 through June 2021).
Nationwide VA COVID-19 admissions peaked in January 2021. Significant increases in the rates of CLABSIs, VAEs, and MRSA all-site HAIs (but not MRSA CLABSIs) were observed during the pandemic in acute-care facilities. There was no significant change in CAUTI rates, and C. difficile rates significantly decreased. There were no significant increases in HAIs in long-term care facilities.
The COVID-19 pandemic had a differential impact on HAIs of various types in VA acute care, with many rates increasing. The decrease in CDI HAIs may be due, in part, to evolving diagnostic testing. The minimal impact of COVID-19 in VA long-term facilities may reflect differences in patient numbers and acuity and early recognition of the impact of the pandemic on nursing home residents leading to increased vigilance and optimization of infection prevention and control practices in that setting. These data support the need for building and sustaining conventional infection prevention and control strategies before and during a pandemic.
A guideline for the prevention of Clostridioides difficile infection (CDI) in 127 Veterans Health Administration acute-care facilities was implemented in July 2012. Beginning in 2015, a targeted assessment for prevention strategy was used to evaluate facilities for hospital-onset healthcare-facility–associated CDIs to focus prevention efforts where they might have the most impact in reaching a reduction goal of 30% nationwide.
We calculated standardized infection ratios (SIRs) and cumulative attributable differences (CADs) using a national data baseline. Facilities were ranked by CAD, and those with the 10 highest CAD values were targeted for periodic conference calls or a site visit from January 2016–September 2019.
The hospital-onset healthcare-facility–associated CDI rate in the 10 facilities with the highest CADs declined 56% during the process improvement period, compared to a 44% decline in the 117 nonintervention facilities (P = .03).
Process improvement interventions targeting facilities ranked by CAD values may be an efficient strategy for decreasing CDI rates in a large healthcare system.
Animal studies indicate that the composition of gut microbiota may be involved in the progression of insulin resistance to type 2 diabetes. Probiotics and/or prebiotics could be a promising approach to improve insulin sensitivity by favourably modifying the composition of the gut microbial community, reducing intestinal endotoxin concentrations and decreasing energy harvest. The aim of the present review was to investigate the effects of probiotics, prebiotics and synbiotics (a combination of probiotics and prebiotics) on insulin resistance in human clinical trials and to discuss the potential mechanisms whereby probiotics and prebiotics improve glucose metabolism. The anti-diabetic effects of probiotics include reducing pro-inflammatory cytokines via a NF-κB pathway, reduced intestinal permeability, and lowered oxidative stress. SCFA play a key role in glucose homeostasis through multiple potential mechanisms of action. Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release of glucagon-like peptide-1 and peptide YY resulting in increased insulin and decreased glucagon secretion, and suppressed appetite. SCFA can decrease intestinal permeability and decrease circulating endotoxins, lowering inflammation and oxidative stress. SCFA may also have anti-lipolytic activities in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation of 5'-AMP-activated protein kinase signalling in muscle and liver tissues. Resistant starch and synbiotics appear to have favourable anti-diabetic effects. However, there are few human interventions. Further well-designed human clinical studies are required to develop recommendations for the prevention of type 2 diabetes with pro- and prebiotics.
To report our experience of the management of patients with primary sinonasal malignant melanoma, and to review the relevant medical literature.
Retrospective review examining treatment and outcomes.
Twenty-four patients were treated between 1982 and 2007. The mean age at presentation was 67.5 years. The overall five-year survival was 30 per cent; mean survival was three years and eight months.
Sinonasal malignant melanoma is associated with a poor outcome, and survival statistics have not improved over the last 40 years. Treatment should include radical surgery wherever possible. Local recurrence is common; radiotherapy may help control this but does not appear to affect overall survival. The limited evidence available suggests that endoscopic removal of sinonasal malignant melanoma is as effective as other local surgical means, but that craniofacial resection remains the ‘gold standard’ for tumours that contact or traverse the skull base. Novel biological treatments are emerging and hold promise for the future.
The occurrence of Mycobacterium bovis infection in cattle herds during the period 1966–92 in two geographically related areas in South-West England is compared. In one area comprising 104 km2 all badgers were systematically destroyed from 1975–81, after which recolonization was allowed; in the other, comprising 116 km2, small scale, statutory badger removal operations were undertaken from 1975 onwards where specific herds were detected with M. bovis infection. In the area with total clearance, no further incidents with M. bovis isolation occurred from 1982–92. Survival analysis and proportional hazards regression indicated that the risk of herds being identified with infection was less once badgers had been cleared from their neighbourhood, whereas it was greater in herds with 50 or more animals, and once cattle in a herd had responded positively to the tuberculin skin test, even though infection with M. bovis was not confirmed subsequently. The study provides further evidence that badgers represent an important reservoir of M. bovis infection for cattle and that badger control is effective in reducing incidents of cattle infection with M. bovis if action is thorough and recolonization is prevented.
In Drosophila melanogaster two alleles at the Third chromosome resistance locus (Tcr; 3–39·6) were isolated in a screen of EMS mutagenized third chromosomes for dominant resistance to dietary α-methyl dopa, α-MD, a structural analogue of DOPA. Both alleles of Tcr are recessive lethals exhibiting partial complementation. Almost half (48·3%) of the Tcr40 / Tcr45 heterozygotes die as embryos but some survive past adult eclosion. Both the embryonic lethal phenotype and the adult phenotype suggest that Tcr is involved in cuticle synthesis. Tcr mutants suppress the lethality of partially complementing alleles at the α-MD hypersensitive locus, l(2)amd. The viability of Tcr40 / Tcr45, however, is not increased by the presence of a l(2)amd allele. The possibility that the Tcr and l(2)amd mutations reveal a catecholamine metabolic pathway involved in cuticle structure is discussed.
A 12-month abattoir study was undertaken from January 2003. We collected 7492 intestinal samples from cattle, sheep and pigs at slaughter. Rectal samples were taken from cattle and sheep and caecal samples from pigs. They were examined for verocytotoxigenic E. coli (VTEC) O157, Salmonella, thermophilic Campylobacter and Yersinia enterocolitica. Data were collected on the animal from which the sample came and this information was analysed to look at potential risk factors for carriage of these organisms. Logistic regression models were run where an adequate number of positive results were available. This revealed that VTEC O157 carriage in cattle was associated with the summer period and that age was a protective factor. Salmonella carriage in pigs was associated with lairage times >12 h, the North East and not feeding when there was no bedding available. In cattle, carriage was associated with the summer period, the Eastern region of GB and dairy animals. In sheep a spring seasonal effect was seen, which coincided with the lambing period. The carriage of thermophilic Campylobacter in cattle was associated with single-species abattoirs, with age a protective factor. In sheep, winter was a risk period with lairage management influential. For pigs, lairage times of <12 h were found to be associated with carriage. A seasonal trend for carriage of Y. enterocolitica in all species was demonstrated with the period December–May a risk. For cattle, age was also a risk factor; for sheep feeding in the lairage and for pigs being held overnight were risk factors.
The Randomized Badger Culling Trial (RBCT) began in 1998 to determine the impact of badger culling in controlling bovine tuberculosis in cattle. A total of 1166 badgers (14% of total) proactively culled during the RBCT were found to be tuberculous, offering a unique opportunity to study the pathology caused by Mycobacterium bovis in a large sample of badgers. Of these, 39% of adults (~6% of all adults culled) had visible lesions (detectable at necropsy) of bovine tuberculosis; cubs had a lower prevalence of infection (9%) but a higher percentage of tuberculous cubs (55·5%) had visible lesions. Only ~1% of adult badgers had extensive, severe pathology. Tuberculous badgers with recorded bite wounds (~5%) had a higher prevalence of visible lesions and a different distribution of lesions, suggesting transmission via bite wounds. However, the predominance of lesions in the respiratory tract indicates that most transmission occurs by the respiratory route.
An abattoir survey was undertaken to determine the prevalence of foodborne zoonotic organisms colonizing cattle, sheep and pigs at slaughter in Great Britain. The study ran for 12 months from January 2003, involved 93 abattoirs and collected 7703 intestinal samples. The design was similar to two previous abattoir surveys undertaken in 1999–2000 allowing comparisons. Samples were examined for VTEC O157, Salmonella, thermophilic Campylobacter and Yersinia enterocolitica. The prevalence of VTEC O157 faecal carriage was 4·7% in cattle, 0·7% in sheep and 0·3% in pigs. A significant decrease in sheep was detected from the previous survey (1·7%). Salmonella carriage was 1·4% in cattle, a significant increase from the previous survey of 0·2%. In sheep, faecal carriage was 1·1% a significant increase from the previous survey (0·1%). In pigs, carriage was 23·4%, consistent with the previous study. Thermophilic Campylobacter spp. were isolated from 54·6% of cattle, 43·8% of sheep and 69·3% of pigs. Y. enterocolitica was isolated from 4·5% of cattle, 8·0% of sheep and 10·2% of pigs.
Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non-bacterial infections were identified in 5·1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4·9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF.