Essential Oils Can Mitigate Adverse Effects of Prolonged Masking in the Hospital Setting.

Adverse symptoms of prolonged masking were reported by personnel. A drop of essential oil was added to the mask to mitigate these effects and significantly lessened symptoms. Symptoms declined by almost half, including anxiety, nausea, and indigestion. This simple intervention can mitigate adverse effects of prolonged masking in the hospital setting.

Culture of Tumorigenic Cells on Protein Fibers Reveals Metastatic Cell Behaviors.

Tumorigenic cell behaviors can be suppressed or enhanced by their physicochemical environment. As a first step toward developing materials that allow tumorigenic behaviors to be observed and manipulated, we cultured related MCF10 breast cell lines on fibers composed of the Drosophila protein Ultrabithorax (Ubx). These cell lines, originally derived from fibrocystic breast tissue, represent a continuum of tumorigenic behavior. Immortal but nontumorigenic MCF10A cells, as well as semitumorigenic MCF10AT cells, attached and spread on Ubx fibers. MCF10CA-1a cells, the most highly transformed line, secreted high concentrations of matrix metalloproteinases when cultured on Ubx materials, resulting in differences in cell attachment and cytoskeletal structure, and enabling invasive behavior. Because the mechanical and functional properties of Ubx fibers can be genetically manipulated, these materials provide a valuable tool for cancer research, allowing creation of diverse microenvironments that allow assessment of invasive, metastatic behavior.

Identification of multiple dityrosine bonds in materials composed of the Drosophila protein Ultrabithorax.

The recombinant protein Ultrabithorax (Ubx), a Drosophila melanogaster Hox transcription factor, self-assembles into biocompatible materials in vitro that are remarkably extensible and strong. Here, we demonstrate that the strength of Ubx materials is due to intermolecular dityrosine bonds. Ubx materials auto-fluoresce blue, a characteristic of dityrosine, and bind dityrosine-specific antibodies. Monitoring the fluorescence of reduced Ubx fibers upon oxygen exposure reveals biphasic bond formation kinetics. Two dityrosine bonds in Ubx were identified by site-directed mutagenesis followed by measurements of fiber fluorescent intensity. One bond is located between the N-terminus and the homeodomain (Y4/Y296 or Y12/Y293), and another bond is formed by Y167 and Y240. Fiber fluorescence closely correlates with fiber strength, demonstrating that these bonds are intermolecular. To our knowledge, this is the first identification of specific residues that participate in dityrosine bonds in protein-based materials. The percentage of Ubx molecules harboring both bonds can be decreased or increased by mutagenesis, providing an additional mechanism to control the mechanical properties of Ubx materials. Duplication of tyrosine-containing motifs in Ubx increases dityrosine content in Ubx fibers, suggesting these motifs could be inserted in other self-assembling proteins to strengthen the corresponding materials.

Genetic variants and susceptibility to neurological complications following West Nile virus infection.

To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(-5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56-.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(-5); OR, 1.47 [95% CI, 1.21-1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(-4); OR, 0.69 [95% CI, .56-.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.

Molecular genetic testing does not improve the detection of fluoroquinolone resistance before transrectal prostate biopsy.

Background: Fluoroquinolone-resistant (FQR) Escherichia coli (E. coli) causes transrectal prostate biopsy infections. We seek to further identify fluoroquinolones resistance by the incorporation of genetic profiling to influence antibiotic selection for transrectal prostate biopsy and whether the addition of this genetic testing could improve the prediction of FQR detection at the time of biopsy. Materials and methods: In this prospective observational cohort study, rectal swabs were collected within 30 days of an upcoming prostate biopsy. These swabs were sent for phenotypic and genotypic assessment to predict FQR on the day of the biopsy. Phenotype: Specimens were inoculated onto MacConkey agar containing ciprofloxacin using standard culture techniques to determine FQR status. Genotype: We compared cultures to polymerase chain reaction (PCR) sequence typing (E.coli- ST131/H30/ST69) and bacterial plasmids (gyrA, qnrQ, and qnrS). The presence of FQR on this testing was compared to the second rectal swab collected just before biopsy (2 hours after ciprofloxacin prophylaxis), which served as the gold standard for FQR. Results: Overall, the FQR rate was 23.6%. The bacterial plasmids (qnr) were present in 54.1% of samples, and multidrug-resistant E. coli ST131 was present in 12.5% of samples. In comparison, phenotypic assessment using rectal culture had a better prediction for the presence of FQR as compared to genotypic testing [area under the curve (AUC) = 0.85 in phenotype arm vs. AUC = 0.45 in genotype arm]. Conclusion: We detected a high prevalence of FQR genes in the rectum, but the addition of PCR-based genotyping did not improve the prediction of culture-based FQR at the time of biopsy.

The Clinical Safety and Effectiveness Course: Ten Years of Experiential Training in Quality Improvement for Practicing Professionals.

Training in quality improvement (QI) and patient safety for clinicians are needed for continued progress in health care quality. A project-based QI curriculum training faculty, residents, and staff in an academic health center for >10 years are reviewed and evaluated. Didactic curriculum includes QI knowledge domains, and QI methods are applied to a project during the course. There are 638 graduates and 239 projects since implementation. Most projects (84%) effected behavior change, change in clinical practice, and benefit to patients. Faculty have used the training to develop formal QI programs for Graduate Medical Education (GME). Graduates value the skills for their professional and personal lives, and for career enhancement. Experiential QI training for practicing professionals is valuable and effective. Collaboration and support from stakeholders are key factors in success. The Clinical Safety & Effectiveness course is a reproducible and relevant model of interprofessional QI education for practicing professionals and staff.

Dose of trimethoprim-sulfamethoxazole to treat skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus.

We undertook this study to investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). A prospective, observational cohort with nested case-control study was performed at a public tertiary health system. Among patients with MRSA SSTIs during the period from May 2008 to September 2008 who received oral monotherapy with TMP/SMX and whose clinical outcome was known, the clinical characteristics and outcomes were compared between patients treated with a high dose of TMP/SMX (320 mg/1,600 mg twice daily) for 7 to 15 days and patients treated with the standard dose of TMP/SMX (160 mg/800 mg twice daily) for 7 to 15 days. In patients with MRSA SSTIs, those treated with the high dose of TMP/SMX (n = 121) had clinical characteristics similar to those of patients treated with the standard dose of TMP/SMX (n = 170). The only exception was a higher proportion of patients with a history of trauma upon admission among the patients treated with the higher dose. The proportion of patients with clinical resolution of infection was not different in the two groups (88/121 [73%] versus 127/170 [75%]; P = 0.79). The lack of significance remained in patients with abscess upon stratified analysis by whether surgical drainage was performed. The study found that patients with MRSA SSTIs treated with the higher dose of TMP/SMX (320/1,600 mg twice daily) for 7 to 15 days had a similar rate of clinical resolution as patients treated with the standard dose of TMP/SMX (160/800 mg twice daily) for 7 to 15 days.

On the design of composite protein-quantum dot biomaterials via self-assembly.

Incorporation of nanoparticles during the hierarchical self-assembly of protein-based materials can impart function to the resulting composite materials. Herein we demonstrate that the structure and nanoparticle distribution of composite fibers are sensitive to the method of nanoparticle addition and the physicochemical properties of both the nanoparticle and the protein. Our model system consists of a recombinant enhanced green fluorescent protein-Ultrabithorax (EGFP-Ubx) fusion protein and luminescent CdSe-ZnS core-shell quantum dots (QDs), allowing us to optically assess the distribution of both the protein and nanoparticle components within the composite material. Although QDs favorably interact with EGFP-Ubx monomers, the relatively rough surface morphology of composite fibers suggests EGFP-Ubx-QD conjugates impact self-assembly. Indeed, QDs templated onto EGFP-Ubx film post-self-assembly can be subsequently drawn into smooth composite fibers. Additionally, the QD surface charge impacts QD distribution within the composite material, indicating that surface charge plays an important role in self-assembly. QDs with either positively or negatively charged coatings significantly enhance fiber extensibility. Conversely, QDs coated with hydrophobic moieties and suspended in toluene produce composite fibers with a heterogeneous distribution of QDs and severely altered fiber morphology, indicating that toluene severely disrupts Ubx self-assembly. Understanding factors that impact the protein-nanoparticle interaction enables manipulation of the structure and mechanical properties of composite materials. Since proteins interact with nanoparticle surface coatings, these results should be applicable to other types of nanoparticles with similar chemical groups on the surface.

Improving health care workers for seasonal influenza vaccination at university health system: a paradigm for closing the quality chasm.

Significant gaps in quality and patient safety in the US health-care system have been identified and were reported in the past decade by the Institute of Medicine. Despite recognition of these gaps in "knowing versus doing," change in health care is slow and difficult. The quality improvement and clinical safety movement is increasing among US medical centers. Our health science center implemented the UT System Clinical Safety and Effectiveness course, providing project-based teaching of quality-improvement tools and principles of patient safety. A quality-improvement project that increased healthcare workers' influenza vaccination rate by 17.8% from that in 2008 to a rate of 76.6% in 2009 serves as a paradigm of how physicians can lead quality-improvement project teams to narrow the quality chasm (1). Local efforts to narrow the chasm are discussed in the present paper, including inter-professional education in quality improvement and clinical safety.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Infection control in the intensive care unit: progress and challenges in systems and accountability.

Attention to the improvement of safety in healthcare lately has focused on healthcare-associated infections, including many that occur in the intensive care unit, such as catheter-related bloodstream infections and ventilator-associated pneumonias. Great strides have been made in decreasing the rates of intensive care unit hospital-acquired infections in the past decade. This is attributable to a number of factors, including standardization of care, technological advances, provider payment reform, and consumer activism. Teamwork and communication remain the most important facets in patient safety. The papers in this supplement examine the roles of human factors and process engineering, survey a spectrum of infection control and safety challenges encountered by critical care practitioners, and assess the future challenges for continued improvement in our systems of care.

Can a regional government's social inclusion initiative contribute to the quest for health equity?

Despite decades of concern about reducing health inequity, the Commission on the Social Determinants of Health (CSDH) painted a picture of persistent and, in some cases, increasing health inequity. It also made a call for increased evaluation of interventions that might reduce inequities. This paper describes such an intervention-the Social Inclusion Initiative (SII) of the South Australian Government-that was documented for the Social Exclusion Knowledge Network of the CSDH. This initiative is designed to increase social inclusion by addressing key determinants of health inequity-in the study period these were education, homelessness and drug use. Our paper examines evidence from a rapid appraisal to determine whether a social inclusion initiative is a useful aspect of government action to reduce health inequity. It describes achievements in each specific area and the ways they can be expected to affect health equity. Our study highlighted four factors central to the successes achieved by the SII. These were the independent authority and influence of the leadership of the SII, the whole of government approach supported by an overarching strategic plan which sets clear goals for government and the clear and unambiguous support from the highest level of government. We conclude that a social inclusion approach can be valuable in the quest to reduce inequities and that further research on innovative social policy approaches is required to examine their likely impact on health equity.

Continuous versus intermittent infusion of oxacillin for treatment of infective endocarditis caused by methicillin-susceptible Staphylococcus aureus.

Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible Staphylococcus aureus (MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's t test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%, P = 0.7) and length of stay (20 versus 25 days, P = 0.4) but differed in 30-day microbiological cure (94% versus 79%, P = 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%, P = 0.2) and 30-day microbiological cure (90% versus 89%, P = 0.8); however, times to defervescence (4 versus 2 days, P = 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA.

Presence and molecular epidemiology of virulence factors in methicillin-resistant Staphylococcus aureus strains colonizing and infecting soldiers.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of skin and soft-tissue infections (SSTI). The understanding of the molecular epidemiology and virulence of MRSA continues to expand. From January 2005 to December 2005, we screened soldiers for MRSA nasal colonization, administered a demographic questionnaire, and monitored them prospectively for SSTI. All MRSA isolates underwent molecular analysis, which included pulsed-filed gel electrophoresis (PFGE) and PCR for Panton-Valentine leukocidin (PVL), the arginine catabolic mobile element (ACME), and the staphylococcal cassette chromosome mec (SCCmec). Of the 3,447 soldiers screened, 134 (3.9%) had MRSA colonization. Of the 3,066 (89%) who completed the study, 39 developed culture-confirmed MRSA abscesses. Clone USA300 represented 53% of colonizing isolates but was responsible for 97% of the abscesses (P < 0.001). Unlike colonizing isolates, isolates positive for USA300, PVL, ACME, and type IV SCCmec were significantly associated with MRSA abscess isolates. As determined by multivariate analysis, risk factors for MRSA colonization were a history of SSTI and a history of hospitalization. Although various MRSA strains may colonize soldiers, USA300 is the most virulent when evaluated prospectively, and PVL, ACME, and type IV SCCmec are associated with these abscesses.

In Vitro Activity of Essential Oils Against Gram-Positive and Gram-Negative Clinical Isolates, Including Carbapenem-Resistant Enterobacteriaceae.

BACKGROUND: There is increasing demand for compounds to treat antimicrobial-resistant pathogens, and essential oils have gained interest. Moreover, previous studies have demonstrated antimicrobial activity of these nonpharmaceutical products. We investigated the activity of essential oils against multiresistant bacteria and other clinical isolates to evaluate the potential of their use topically and/or internally for treatment of bacterial infections. METHODS: We studied the in vitro activity of 10 essential oils and 1 essential oil blend against clinical isolates including extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. RESULTS: Essential oils of oregano, thyme, cinnamon bark, and lemongrass had the largest zones of inhibition against Gram-positive organisms, whereas cinnamon bark had the largest zone of inhibition against P aeruginosa. Oregano, thyme, and cinnamon bark had the largest zones of inhibition against Enterobacteriaceae. CONCLUSIONS: Essential oils have promising in vitro activity that warrants further study of their activity and use in the clinical setting.

Microbiome diversity in carriers of fluoroquinolone resistant Escherichia coli.

Purpose: Fluoroquinolone-resistant (FQR) Escherichia coli causes transrectal prostate biopsy infections. In order to reduce colonization of these bacteria in carriers, we would like to understand the surrounding microbiome to determine targets for decolonization. Materials and Methods: We perform an observational study to investigate the microbiome differences in men with and without FQR organisms found on rectal culture. A rectal swab with two culturettes was performed on men before an upcoming prostate biopsy procedure as standard of care to perform "targeted prophylaxis." Detection of FQR was performed by the standard microbiology lab inoculates the swab onto MacConkey agar containing ciprofloxacin. The extra swab was sent for 16S rRNA amplicon sequencing (MiSeq paired-end) using the V1V2 primer. Alpha and beta-diversity analysis were performed using QIIME. We used PERMANOVA to evaluate the statistical significance of beta-diversity distances within and between groups of interest. Results: We collected 116 rectal swab samples before biopsy for 16S rRNA amplicon sequencing. We identified 18 isolates (15.5%, 18/116) that were positive and had relative reduced diversity profiles (p<0.05). Enterobacteriaceae were significantly over-represented in the FQR subjects (adjusted p=0.03). Conclusions: Microbiome analysis determined that men colonized with FQR bacteria have less diverse bacterial communities (dysbiosis), higher levels of Enterobacteriaceae and reduced levels of Prevotella disiens. These results may have implications in pre/probiotic intervention studies.

Responding to simulated pandemic influenza in San Antonio, Texas.

OBJECTIVE: To describe the results of a simulation study of the spread of pandemic influenza, the effects of public health measures on the simulated pandemic, and the resultant adequacy of the surge capacity of the hospital infrastructure and to investigate the adequacy of key elements of the national pandemic influenza plan to reduce the overall attack rate so that surge capacity would not be overwhelmed. DESIGN: We used 2 discrete-event simulation models: the first model simulates the contact and disease transmission process, as affected by public health interventions, to produce a stream of arriving patients, and the second model simulates the diagnosis and treatment process and determines patient outcomes. SETTING: Hypothetical scenarios were based on the response plans, infrastructure, and demographic data of the population of San Antonio, Texas. RESULTS: Use of a mix of strategies, including social distancing, antiviral medications, and targeted vaccination, may limit the overall attack rate so that demand for care would not exceed the capacity of the infrastructure. Additional simulations to assess social distancing as a sole mitigation strategy suggest that a reduction of infectious community contacts to half of normal levels would have to occur within approximately 7 days. CONCLUSIONS: Under ideal conditions, the mix of strategies may limit demand, which can then be met by community surge capacity. Given inadequate supplies of vaccines and antiviral medications, aggressive social distancing alone might allow for the control of a local epidemic without reliance on outside support.

Correlation between respiratory colonization with gram-negative bacteria and development of gram-negative bacterial infection after cardiac surgery.

This pilot, observational study involving 286 patients who underwent cardiac surgery found that patients who had endotracheal colonization with gram-negative bacteria at 1 week after surgery were more likely to develop subsequent infection compared to those without colonization (8 of 23 vs. 4 of 40; relative risk 2.3 [95% confidence interval, 1.3-4.1; P value <.05]).

Diminished vancomycin and daptomycin susceptibility during prolonged bacteremia with methicillin-resistant Staphylococcus aureus.

An elderly patient with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was treated sequentially with vancomycin plus rifampin then daptomycin plus gentamicin. The MRSA strain developed diminished susceptibility to vancomycin (MIC increase and tolerance), daptomycin, and gentamicin, and resistance to rifampin during therapy.

Living the mission: medical assistance to Nigeria.

In 2001, a team of health care providers from Tennessee undertook a medical mission to the Nigerian Christian Hospital in Aba, Nigeria. During A 10-day period, the surgical team applied US and AORN standards when possible, but found they also had to accept some of the local standards because of the lack of medical supplies, cleaning supplies, and properly functioning equipment in this impoverished area. The 60 surgeries performed by the team was a small number relative to the community's overwhelming needs, but the team members were rewarded with the knowledge that they had helped many patients by providing them with quality care that normally would have been unavailable.