The public health exposome and pregnancy-related mortality in the United States: a high-dimensional computational analysis.

BACKGROUND: Racial inequities in maternal mortality in the U.S. continue to be stark. METHODS: The 2015-2018, 4-year total population, county-level, pregnancy-related mortality ratio (PRM; deaths per 100,000 live births; National Center for Health Statistics (NCHS), restricted use mortality file) was linked with the Public Health Exposome (PHE). Using data reduction techniques, 1591 variables were extracted from over 62,000 variables for use in this analysis, providing information on the relationships between PRM and the social, health and health care, natural, and built environments. Graph theoretical algorithms and Bayesian analysis were applied to PHE/PRM linked data to identify latent networks. RESULTS: PHE variables most strongly correlated with total population PRM were years of potential life lost and overall life expectancy. Population-level indicators of PRM were overall poverty, smoking, lack of exercise, heat, and lack of adequate access to food. CONCLUSIONS: In this high-dimensional analysis, overall life expectancy, poverty indicators, and health behaviors were found to be the strongest predictors of pregnancy-related mortality. This provides strong evidence that maternal death is part of a broader constellation of both similar and unique health behaviors, social determinants and environmental exposures as other causes of death.

Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.

Altered stimulus representation in rat auditory cortex is not causal for loss of consciousness under general anaesthesia.

BACKGROUND: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. METHODS: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. RESULTS: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Microcalcifications in breast cancer: From pathophysiology to diagnosis and prognosis.

The implementation of mammographic screening programmes in many countries has been linked to a marked increase in early detection and improved prognosis for breast cancer patients. Breast tumours can be detected by assessing several features in mammographic images but one of the most common are the presence of small deposits of calcium known as microcalcifications, which in many cases may be the only detectable sign of a breast tumour. In addition to their efficacy in the detection of breast cancer, the presence of microcalcifications within a breast tumour may also convey useful prognostic information. Breast tumours with associated calcifications display an increased rate of HER2 overexpression as well as decreased survival, increased risk of recurrence, high tumour grade and increased likelihood of spread to the lymph nodes. Clearly, the presence of microcalcifications in a tumour is a clinically significant finding, suggesting that a detailed understanding of their formation may improve our knowledge of the early stages of breast tumourigenesis, yet there are no reports which attempt to bring together recent basic science research findings and current knowledge of the clinical significance of microcalcifications. This review will summarise the most current understanding of the formation of calcifications within breast tissue and explore their associated clinical features and prognostic value.

The interaction of the Chrna5 D398N variant with developmental nicotine exposure.

A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an aspartic acid [D] to asparagine [N] at position 398 of the human α5 nicotinic acetylcholine receptor subunit) has been associated with increased risk for nicotine dependence. Consequently, carriers of the risk variant may be at elevated risk for in utero nicotine exposure. To assess whether this gene-environment interaction might impact nicotine intake in developmental nicotine-exposed offspring, we utilized a mouse expressing this human SNP. D and N dams drank nicotine (100 µg/mL) in 0.2% saccharin water or 0.2% saccharin water alone (vehicle) as their sole source of fluid from 30 days prior to breeding until weaning of offspring. The nicotine (D Nic, N Nic) or vehicle (D Veh, N Veh) exposed offspring underwent a 2-bottle choice test between postnatal ages of 30 to 46 days. N Nic offspring consumed the most nicotine at the highest concentration (400 µg/mL) compared with all other groups. In contrast, D Nic offspring drank the least amount of nicotine at all concentrations tested. Nicotine-stimulated dopamine (DA) release measured from striatal synaptosomes was increased in D Nic offspring, while decreased in N Nic offspring relative to their genotype-matched controls. These data suggest that the α5 variant influences the effect of developmental nicotine exposure on nicotine intake of exposed offspring. This gene-environment interaction on striatal DA release may provide motivation for increased nicotine seeking in N Nic offspring and reduced consumption in D Nic offspring.

Supervised toothbrushing programs in primary schools and early childhood settings: A scoping review.

OBJECTIVE: In this article we report the findings of a scoping review that aimed to identify and summarise the range of programs and guidelines available for toothbrushing programs in schools and early childhood settings. Dental caries is one of the most common preventable diseases affecting children worldwide. Untreated caries can impact on child health and wellbeing, development, socialisation and school attendance. Supervised toothbrushing programs in schools and other early childhood settings can be effective in improving the oral health of young children. There is limited understanding of the salient issues to consider when developing such programs or how they are best implemented in real world settings. METHODS: A scoping review methodology was utilised to provide a summary of the guidelines and programs available. Key search terms were developed, mapped and utilised to identify guidelines and programs across 6 databases and key search engines. RESULTS: We located 26 programs and guidelines that met the inclusion and exclusion criteria for the review. These were collated and summarised across key countries and critical aspects of program development and implementation were identified. Toothbrush type and storage, toothpaste strength and method of dispensing, toothbrush storage, staff training and parental consent are key considerations that varied widely. CONCLUSIONS AND RECOMMENDATIONS: Guidelines for supervised toothbrushing programs vary within and across countries due to differences in water fluoridation and availability of low fluoride toothpastes. The results of this review provide critical information to be considered when establishing and implementing toothbrushing programs in these settings.

Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium.

BACKGROUND: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. OBJECTIVE: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. METHODS: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. RESULTS: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. CONCLUSIONS: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

Training Effectiveness of a Wide Area Virtual Environment in Medical Simulation.

INTRODUCTION: The success of war fighters and medical personnel handling traumatic injuries largely depends on the quality of training they receive before deployment. The purpose of this study was to gauge the utility of a Wide Area Virtual Environment (WAVE) as a training adjunct by comparing and evaluating student performance, measuring sense of realism, and assessing the impact on student satisfaction with their training exposure in an immersive versus a field environment. METHODS: This comparative prospective cohort study examined the utility of a three-screen WAVE where subjects were immersed in the training environment with medical simulators. Standard field training commenced for the control group subjects. Medical skills, time to completion, and Team Strategies and Tools to Enhance Performance and Patient Safety objective metrics were assessed for each team (n = 94). In addition, self-efficacy questionnaires were collected for each subject (N = 470). RESULTS: Medical teams received poorer overall team scores (F1,186 = 0.756, P = 0.001), took longer to complete the scenario (F1,186 = 25.15, P = 0.001), and scored lower on The National Registry of Emergency Medical Technicians trauma assessment checklist (F1,186 = 1.13, P = 0.000) in the WAVE versus the field environment. Critical thinking and realism factors within the self-efficacy questionnaires scored higher in the WAVE versus the field [(F1,466 = 8.04, P = 0.005), (F1,465 = 18.57, P = 0.000), and (F1,466 = 53.24, P = 0.000), respectively]. CONCLUSIONS: Environmental and emotional stressors may negatively affect critical thinking and clinical skill performance of medical teams. However, by introducing more advanced simulation trainings with added stressors, students may be able to adapt and overcome barriers to performance found in high-stress environments.

Polymeric prodrug combination to exploit the therapeutic potential of antimicrobial peptides against cancer cells.

Antimicrobial Peptides (AMPs) have unique anticancer properties, but their clinical application is currently limited by an inadequate margin of safety. A prodrug strategy associated with a combination therapy approach could address this limitation by increasing their therapeutic index and their efficacy. Accordingly, the first targeted anticancer polymeric prodrug candidates of AMPs, intended for combination therapy with another polymeric prodrug of an approved antineoplastic agent (doxorubicin), were synthesized as either a PEG-based dual-release prodrug or two individual pegylated prodrugs. The latter are based on a cathepsin B-labile peptide linker and an acid-sensitive acyl hydrazone bond for the AMP and doxorubicin prodrugs, respectively. Anticancer activities and toxicity differentials achieved with the free peptide and its polymer conjugates against ovarian, cancer and non-malignant, cells, indicate that protease-dependent reversible pegylation could be implemented to increase the therapeutic indices of AMPs in cancer therapy. The results obtained also show that this approach can be developed if the releasable PEG linker can be optimised to conciliate the attributes and restrictions of pegylation against proteases. In addition, combination of the polymeric prodrugs of the AMP and of doxorubicin provides additive antitumor effects which could be exploited to enhance the efficacy of the AMP candidate.

Assessing community resilience: A CART survey application in an impoverished urban community.

This article describes an application of the Communities Advancing Resilience Toolkit (CART) Assessment Survey which has been recognized as an important community tool to assist communities in their resilience-building efforts. Developed to assist communities in assessing their resilience to disasters and other adversities, the CART survey can be used to obtain baseline information about a community, to identify relative community strengths and challenges, and to re-examine a community after a disaster or post intervention. This article, which describes an application of the survey in a community of 5 poverty neighborhoods, illustrates the use of the instrument, explicates aspects of community resilience, and provides possible explanations for the results. The paper also demonstrates how a community agency that serves many of the functions of a broker organization can enhance community resilience. Survey results suggest various dimensions of community resilience (as represented by core CART community resilience items and CART domains) and potential predictors. Correlates included homeownership, engagement with local entities/activities, prior experience with a personal emergency or crisis while living in the neighborhood, and involvement with a community organization that focuses on building safe and caring communities through personal relationships. In addition to influencing residents' perceptions of their community, it is likely that the community organization, which served as a sponsor for this application, contributes directly to community resilience through programs and initiatives that enhance social capital and resource acquisition and mobilization.

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis.

Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990-1991 Persian Gulf War were afflicted. Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined. Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME. To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls. Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters. These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.

Revisiting perceptions of quality of hospice care: managing for the ultimate referral.

Hospice services provided in the final months of life are delivered through complex interpersonal relationships between caregivers, patients, and families. Often, service value and quality are defined by these interpersonal interactions. This understanding provides hospice leaders with an enormous opportunity to create processes that provide the optimal level of care during the last months of life. The authors argue that the ultimate referral is attained when a family member observes the care of a loved one, and the family member conveys a desire to receive the same quality of services their loved one received at that facility. The point of this article is to provide evidence that supports the methods to ultimately enhance the patient's and family's experience and increase the potential for the ultimate referral.

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat.

Exposure to intrauterine growth restriction (IUGR) is an important risk factor for impaired learning and memory, particularly in males. Although the basis of IUGR-associated learning and memory dysfunction is unknown, potential molecular participants may be insulin-like growth factor 1 (Igf1) and its receptor, IGF1r. We hypothesized that transcript levels and protein abundance of Igf1 and IGF1r in the hippocampus, a brain region critical for learning and memory, would be lower in IUGR male rats than in age-matched male controls at birth (postnatal day 0, P0), at weaning (P21) and adulthood (P120). We also hypothesized that changes in messenger Ribonucleic acid (mRNA) transcript levels and protein abundance would be associated with specific histone marks in IUGR male rats. Lastly, we hypothesized that IUGR male rats would perform poorer on tests of hippocampal function at P120. IUGR was induced by bilateral ligation of the uterine arteries in pregnant dams at embryonic day 19 (term is 21 days). Hippocampal Igf1 mRNA transcript levels and protein abundance were unchanged in IUGR male rats at P0, P21 or P120. At P0 and P120, IGF1r expression was increased in IUGR male rats. At P21, IGF1r expression was decreased in IUGR male rats. Increased IGF1r expression was associated with more histone 3 lysine 4 dimethylation (H3K4Me2) in the promoter region. In addition, IUGR male rats performed poorer on intermediate-term spatial working memory testing at P120. We speculate that altered IGF1r expression in the hippocampus of IUGR male rats may play a role in learning and memory dysfunction later in life.

Free-text comments: understanding the value in family member descriptions of hospice caregiver relationships.

Invitations for free-text comments on surveys provide family members of hospice patients an opportunity to "tell" their story of the hospice experience and caregiver relationships during the last months of life. These comments are a rich source of data for understanding the complex interpersonal relationships that influence patient/family perceptions of both quality of care and quality of life. Analysis of 438 free-text comments provided by 243 hospice family members revealed 5 emergent caregiver relationship themes: knowledge, skills, and abilities; empathy and compassion; trust and acceptance; communication experience and time spent with caregiver. Findings support the value of free-text comments to explain or add depth to quality assessments, modify therapeutic interventions, and identify strategies for process improvement that advance hospice quality of care.

Nicotinic cholinergic mechanisms causing elevated dopamine release and abnormal locomotor behavior.

Firing rates of dopamine (DA) neurons in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) control DA release in target structures such as striatum and prefrontal cortex. DA neuron firing in the soma and release probability at axon terminals are tightly regulated by cholinergic transmission and nicotinic acetylcholine receptors (nAChRs). To understand the role of α6* nAChRs in DA transmission, we studied several strains of mice expressing differing levels of mutant, hypersensitive (leucine 9' to serine [L9'S]) α6 subunits. α6 L9'S mice harboring six or more copies of the hypersensitive α6 gene exhibited spontaneous home-cage hyperactivity and novelty-induced locomotor activity, whereas mice with an equal number of WT and L9'S α6 genes had locomotor activity resembling that of control mice. α6-dependent, nicotine-stimulated locomotor activation was also more robust in high-copy α6 L9'S mice versus low-copy mice. In wheel-running experiments, results were also bi-modal; high-copy α6 L9'S animals exhibited blunted total wheel rotations during each day of a 9-day experiment, but low-copy α6 L9'S mice ran normally on the wheel. Reduced wheel running in hyperactive strains of α6 L9'S mice was attributable to a reduction in both overall running time and velocity. ACh and nicotine-stimulated DA release from striatal synaptosomes in α6 L9'S mice was well-correlated with behavioral phenotypes, supporting the hypothesis that augmented DA release mediates the altered behavior of α6 L9'S mice. This study highlights the precise control that the nicotinic cholinergic system exerts on DA transmission and provides further insights into the mechanisms and consequences of enhanced DA release.

Recollection of hypoxia symptoms between training events.

INTRODUCTION: The well-established technique of mask-off hypoxia training in a hypobaric training environment elicits symptoms that are correlated with in-flight symptoms reported by aircrew. Aircrew receive training on recognition of symptoms and response early in their flying career and accomplish refresher training on a 5-yr cycle. The symptoms reported after acute hypoxia represent cognitive and psychomotor impairment. The purpose of this study was to evaluate the correlation of symptoms experienced during hypoxia training and recall of symptoms S from the training sessions 5 yr previously. METHODS: A survey listing 18 symptoms of hypoxia and severity of condition was presented to 1123 aircrew attending refresher training at 10 U.S. Air Force Aerospace Physiology Training Units prior to and immediately following hypoxia training in the hypobaric chamber. RESULTS: The five symptoms most commonly reported following hypoxia training are: lightheaded/dizzy, dizziness, mental confusion, visual impairment, and tingling. The hypoxia symptom "lightheaded/dizzy" recorded the highest frequency of all 18 symptoms. Lightheaded/dizzy frequencies for both previous and current hypoxia training were 67.2% and 72.3%, respectively. This symptom remained consistent throughout all data analysis, retaining the highest frequency in all levels of severity (mild, moderate, and extreme) for both the previous hypoxia training and current hypoxia training. DISCUSSION: The similarity of symptoms recalled between hypoxia training events provides strong evidence that hypoxia training is an effective method of establishing recognized decrements that may influence performance in flight.

Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model improves long-term outcomes on bone.

OBJECTIVES: Neonatal stress impairs postnatal bone mineralization. Evidence suggests that mechanical tactile stimulation (MTS) in early life decreases stress hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is impacted by stress and essential to bone development. We hypothesized that MTS administered during neonatal stress would improve bone phenotype in later life. We also predicted an increase in bone specific mRNA expression of IGF1 related pathways. METHODS: Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth hormone receptor (GHR) were measured. RESULTS: Stress resulted in reduced bone area and bone mineral content (BMC) compared to naive control (CTL). MTS intervention increased BMC and tibial growth plate width compared to STRESS. MTS also resulted in higher osteocalcin, and, in males, lower TRAP (p<0.05). MTS resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R, and GHR, respectively (p ≤ 0.001) compared to STRESS. CONCLUSIONS: MTS in early postnatal life improves long-term bone mineralization. IGF1 and related pathways may explain improved BMC.

Understanding the association between employee satisfaction and family perceptions of the quality of care in hospice service delivery.

Families often draw their conclusions about the quality of care received by a family member during the last months of life from their interactions with professional caregivers. A more comprehensive understanding of how these relationships influence the care experience should include an investigation of the association between employee job satisfaction and family perception of the quality of care. This cross-sectional study investigated the association at a regional hospice. Using the Kendall's tau correlation, employee satisfaction scores for care teams trended toward a positive correlation with family overall satisfaction scores from the Family Evaluation of Hospice Care (tau=0.47, P=0.10). A trend for differences in employee satisfaction between the care teams to associate with differences in overall family perceptions of the quality of care also was found using the Kruskal-Wallis analysis of variance (chi(2)(K-W)=9.236, P=0.075). Post hoc tests indicated that overall family perceptions of quality of care differed between the hospice's Residence Team and Non-Hospice Facilities Team. Finally, positive associations between employee satisfaction and the families' Intent to recommend hospice (tau=0.55, P=0.059) and Inform and communicate about patient (tau=0.55, P=0.059) were noted. Selected employee and family comments provide complementarity to further clarify or explain the respondent data. These results suggest that employee satisfaction is associated with family perceptions of the quality of hospice care. Opportunities for improving both employee job satisfaction and family perceptions of the quality of care are discussed.

Mechanistic studies of the immunochemical termination of self-tolerance with unnatural amino acids.

For more than 2 centuries active immunotherapy has been at the forefront of efforts to prevent infectious disease [Waldmann TA (2003) Nat Med 9:269-277]. However, the decreased ability of the immune system to mount a robust immune response to self-antigens has made it more difficult to generate therapeutic vaccines against cancer or chronic degenerative diseases. Recently, we showed that the site-specific incorporation of an immunogenic unnatural amino acid into an autologous protein offers a simple and effective approach to overcome self-tolerance. Here, we characterize the nature and durability of the polyclonal IgG antibody response and begin to establish the generality of p-nitrophenylalanine (pNO(2)Phe)-induced loss of self-tolerance. Mutation of several surface residues of murine tumor necrosis factor-alpha (mTNF-alpha) independently to pNO(2)Phe leads to a T cell-dependent polyclonal and sustainable anti-mTNF-alpha IgG autoantibody response that lasts for at least 40 weeks. The antibodies bind multiple epitopes on mTNF-alpha and protect mice from severe endotoxemia induced by lipopolysaccharide (LPS) challenge. Immunization of mice with a pNO(2)Phe(43) mutant of murine retinol-binding protein (RBP4) also elicited a high titer IgG antibody response, which was cross-reactive with wild-type mRBP4. These findings suggest that this may be a relatively general approach to generate effective immunotherapeutics against cancer-associated or other weakly immunogenic antigens.

A double-blind, randomized, controlled trial of topical polysporin triple compound versus topical mupirocin for the eradication of colonization with methicillin-resistant Staphylococcus aureus in a complex continuing care population.

BACKGROUND: Intranasal mupirocin or Polysporin Triple (PT) ointment (polymyxin B, bacitracin, gramicidin), in combination with chlorhexidine body washes, have been used for eradicating methicillin-resistant Staphylococcus aureus (MRSA), but no comparative studies have been done. METHODS: A double-blind, randomized, controlled clinical trial to compare the efficacy of mupirocin versus PT ointment in combination with chlorhexidine body washes in eradicating MRSA carriage was conducted. Asymptomatic MRSA carriers, medically stable and at least 18 years of age who were patients on medical wards, received twice daily application of either mupirocin or PT ointment to the anterior nares plus once daily 2% chlorhexidine body washes for seven days. Follow-up swabs from multiple sites using broth enrichment were conducted at 48 h, and one, two, four, eight and 12 weeks. RESULTS: Of 103 patients eligible for analysis (54 mupirocin; 49 PT), no significant differences between the two groups with respect to baseline demographics, risk factors for MRSA or MRSA colonization sites were noted. At 48 h, 35 of 54 (65%) patients in the mupirocin group versus 15 of 49 (31%) in the PT group (P=0.001) were found to be MRSA negative at all sites. Significant differences were observed at one and two weeks but were not maintained at other intervals. In those with complete microbiological follow-up, MRSA eradication at all sites occurred in 12 of 39 (30.8%) mupirocin- and one of 36 (2.8%) PT-treated patients (P=0.001). CONCLUSION: Both agents demonstrated poor efficacy and PT was significantly less efficacious than mupirocin at 12 weeks in eradicating MRSA from all sites.