ABSTRACT
BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Humans , Mupirocin/therapeutic use , Chlorhexidine/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Patient Discharge , Aftercare , Staphylococcal Infections/drug therapy , Staphylococcal Infections/prevention & control , Carrier State/drug therapy , Carrier State/prevention & control , Drug Resistance, Microbial , HospitalsABSTRACT
Circular RNAs (circRNAs) has been shown to play an important role in the progression of various cancers. However, the function and underlying mechanisms of circRNAs affecting chemotherapy resistance in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In this study, we used gefitinib-resistant (GR) ESCC cells to investigate the function of circPSMC3 and clarify the underlying mechanism in chemotherapy resistance in ESCC. The results suggested that circPSMC3 expression was downregulated, but miR-10a-5p was upregulated in ESCC tissues and cells, as well as in GR ESCC cells. CircPSMC3 overexpression increased the sensitivity of ESCC cells to gefitinib, as indicated by reduced half maximal inhibitory concentration value, increased apoptosis rate and cleaved caspase-3 protein expression. CircPSMC3 directly interacted with miR-10a-5p and inhibited the expression of miR-10a-5p. Phosphatase and tensin homolog (PTEN) was a direct target of miR-10a-5p and circPSMC3 promoted PTEN expression via decreasing miR-10a-5p level. Moreover, the effect of circPSMC3 on resistance of GR ESCC cells to gefitinib was remarkably reduced by restoration of miR-10a-5p and downregultion of PTEN. Taken together, these observations suggested that upregulation of circPSMC3 overcame resistance of GR ESCC cells to gefitinib by modulating the miR-10a-5p/PTEN axis, which provide a new therapeutic strategy for overcoming gefitinib resistance in ESCC.
Subject(s)
Drug Resistance, Neoplasm/genetics , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gefitinib/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , MicroRNAs/metabolism , PTEN Phosphohydrolase/metabolism , RNA, Circular/metabolism , Base Sequence , Cell Line, Tumor , Down-Regulation/drug effects , Down-Regulation/genetics , Drug Resistance, Neoplasm/drug effects , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Humans , MicroRNAs/genetics , RNA, Circular/genetics , Receptors, Glucocorticoid/metabolism , Up-Regulation/drug effects , Up-Regulation/geneticsABSTRACT
BACKGROUND: Recent evidence suggests that long non-coding RNAs (lncRNAs) are emerging as key determinants of esophageal squamous cell carcinoma (ESCC) progression. This study aimed to investigate the role of lncRNA UPK1A antisense RNA 1 (UPK1A-AS1) in ESCC cell proliferation, invasion, and migration. METHODS: The expression levels of UPK1A-AS1 and miR-1248 were determined using quantitative reverse transcriptase-polymerase chain reaction. The functional role of UPK1A-AS1 in ESCC was investigated using subcellular localization assay, Cell Counting Kit-8 assay, colony formation assay, scratch-healing assay, and transwell invasion assay. The functional interaction between UPK1A-AS1 and miR-1248 was assessed using luciferase reporter and RNA pull-down assays. RESULTS: Twenty dysregulated lncRNAs were detected in ESCC. Downregulation of UPK1A-AS1 was observed in ESCC tissues and cell lines. Functionally, upregulation of UPK1A-AS1 suppressed the proliferation, migration, and invasion of ESCC cells. Moreover, an inverse correlation between UPK1A-AS1 and miR-1248 expression was observed in ESCC specimens, and miR-1248 was identified as a direct target of UPK1A-AS1. Furthermore, we found that UPK1A-AS1 exerts its anti-cancer effects partially through sponging miR-1248 in ESCC cells. CONCLUSION: UPK1A-AS1 suppressed the proliferation, migration, and invasion of ESCC cells partially by sponging miR-1248. Hence, our findings provide novel insights into the regulatory pathway involved in ESCC development.
ABSTRACT
BACKGROUND: Clinical testing detects a fraction of carbapenem-resistant Enterobacteriaceae (CRE) carriers. Detecting a greater proportion could lead to increased use of infection prevention and control measures but requires resources. Therefore, it is important to understand the impact of detecting increasing proportions of CRE carriers. METHODS: We used our Regional Healthcare Ecosystem Analyst-generated agent-based model of adult inpatient healthcare facilities in Orange County, California, to explore the impact that detecting greater proportions of carriers has on the spread of CRE. RESULTS: Detecting and placing 1 in 9 carriers on contact precautions increased the prevalence of CRE from 0% to 8.0% countywide over 10 years. Increasing the proportion of detected carriers from 1 in 9 up to 1 in 5 yielded linear reductions in transmission; at proportions >1 in 5, reductions were greater than linear. Transmission reductions did not occur for 1, 4, or 5 years, varying by facility type. With a contact precautions effectiveness of ≤70%, the detection level yielding nonlinear reductions remained unchanged; with an effectiveness of >80%, detecting only 1 in 5 carriers garnered large reductions in the number of new CRE carriers. Trends held when CRE was already present in the region. CONCLUSION: Although detection of all carriers provided the most benefits for preventing new CRE carriers, if this is not feasible, it may be worthwhile to aim for detecting >1 in 5 carriers.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carrier State/diagnosis , Enterobacteriaceae Infections/transmission , Infection Control/methods , Carrier State/epidemiology , Carrier State/transmission , Contact Tracing , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Hospitals/statistics & numerical data , Humans , Nursing Homes/statistics & numerical data , PrevalenceABSTRACT
AIMS: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) has been shown to be upregulated in esophageal squamous cell carcinoma (ESCC). However, its detailed function in ESCC remains unknown. We investigated its specific roles in ESCC cell proliferation, invasion, and migration. METHODS: Gene expression was evaluated by quantitative reverse transcriptase polymerase chain reaction and western blot. The subcellular localization of lncRNA SNHG6 was determined using subcellular location assay. Luciferase reporter assay and RNA pull-down assay were applied to determine the interaction between lncRNA SNHG6, miR-186-5p, and hypoxia-inducible factor 1α (HIF1α). The cell proliferation, migration, and invasion abilities were evaluated by using cell count kit-8, colony formation assay, and transwell migration and invasion assays. RESULTS: LncRNA SNHG6 and HIF1α were upregulated, while miR-186-5p was downregulated in ESCC tissues and cell lines. Knockdown of lncRNA SNHG6 inhibits ESCC cell proliferation, migration, and invasion. A negative correlation between lncRNA SNHG6 and miR-186-5p expression was found in ESCC tissues. Similarly, there is a positive correlation between lncRNA SNHG6 and HIF1α expression in ESCC tissues. Conversely, miR-186-5p expression was negatively correlated with HIF1α expression in ESCC tissues. Furthermore, lncRNA SNHG6 was identified as a decoy for miR-186-5p, thereby promoting the expression of miR-186-5p target HIF1α. More significantly, restoration of SNHG6 or HIF1α could reverse the inhibitory effect of miR-186-5p on ESCC cell proliferation, migration, and invasion. CONCLUSIONS: Downregulation of SNHG6 inhibited the proliferation, migration, and invasion of ESCC cells through regulating miR-186-5p/HIF1α axis, providing a novel therapeutic target for ESCC.
Subject(s)
Cell Movement , Cell Proliferation , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Disease Progression , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , MicroRNAs/genetics , Neoplasm Invasiveness , RNA, Long Noncoding/genetics , Signal TransductionABSTRACT
BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Local/therapeutic use , Chlorhexidine/therapeutic use , Disinfection , Methicillin-Resistant Staphylococcus aureus , Mupirocin/therapeutic use , Staphylococcal Infections/drug therapy , Administration, Intranasal , Adult , Aged , Carrier State , Comorbidity , Disease Transmission, Infectious/prevention & control , Female , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Hygiene/education , Infection Control/methods , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Patient Education as Topic , Staphylococcal Infections/prevention & control , Staphylococcal Infections/transmissionABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is known as a key molecule to induce cancer cell apoptosis, has also been found to participate in the process of ischemia/reperfusion (I/R) injury. Infiltrated macrophages play dual roles in inflammatory injury and healing following I/R. Whether TRAIL has any effect on macrophages during this process remains elusive. Here we showed that I/R triggered the expressions of TRAIL, DR5 and cytokines (IL-1ß, TNFα, CCL-2 and ICAM-1), in addition to macrophage infiltration, which could be abolished by TRAIL neutralizing antibody. In vitro, TRAIL enhanced DR5 expression and facilitated the macrophages migration following hypoxia/reoxygenation (H/R) treatment in a dose-dependent manner via ER stress and NF-κB signaling pathways, which is accompanied by inflammatory factors expression. The increased cytokines production (such as TNFα and IL-1ß) stimulated by TRAIL can be blocked by the NF-κB and ER stress inhibitor. The results also suggested that NF-κB activation of macrophages during H/R was regulated by ER stress. Thus, our research present that TRAIL affects functional activities of macrophages during I/R injury, which may be a potential therapeutic target for ischemic heart disease.
Subject(s)
Macrophages/metabolism , Myocardial Ischemia/metabolism , NF-kappa B/metabolism , Reperfusion Injury/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Cell Movement/immunology , Cytokines/biosynthesis , Endoplasmic Reticulum Stress/immunology , Flow Cytometry , Immunoblotting , Immunohistochemistry , Macrophages/immunology , NF-kappa B/immunology , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reperfusion Injury/immunology , TNF-Related Apoptosis-Inducing Ligand/immunologyABSTRACT
A recent trial showed that universal decolonization in adult intensive care units (ICUs) resulted in greater reductions in all bloodstream infections and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) than either targeted decolonization or screening and isolation. Since regional health-care facilities are highly interconnected through patient-sharing, focusing on individual ICUs may miss the broader impact of decolonization. Using our Regional Healthcare Ecosystem Analyst simulation model of all health-care facilities in Orange County, California, we evaluated the impact of chlorhexidine baths and mupirocin on all ICU admissions when universal decolonization was implemented for 25%, 50%, 75%, and 100% of ICU beds countywide (compared with screening and contact precautions). Direct benefits were substantial in ICUs implementing decolonization (a median 60% relative reduction in MRSA prevalence). When 100% of countywide ICU beds were decolonized, there were spillover effects in general wards, long-term acute-care facilities, and nursing homes resulting in median 8.0%, 3.0%, and 1.9% relative MRSA reductions at 1 year, respectively. MRSA prevalence decreased by a relative 3.2% countywide, with similar effects for methicillin-susceptible S. aureus. We showed that a large proportion of decolonization's benefits are missed when accounting only for ICU impact. Approximately 70% of the countywide cases of MRSA carriage averted after 1 year of universal ICU decolonization were outside the ICU.
Subject(s)
Cross Infection/prevention & control , Disinfection/methods , Infection Control/statistics & numerical data , Intensive Care Units , Methicillin-Resistant Staphylococcus aureus/growth & development , Staphylococcal Infections/prevention & control , Adult , Anti-Infective Agents/therapeutic use , Beds/microbiology , California/epidemiology , Chlorhexidine/therapeutic use , Computer Simulation , Cross Infection/microbiology , Cross Infection/transmission , Humans , Infection Control/methods , Methicillin-Resistant Staphylococcus aureus/immunology , Mupirocin/therapeutic use , Staphylococcal Infections/microbiology , Staphylococcal Infections/transmissionABSTRACT
Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half.
Subject(s)
Cross Infection/epidemiology , Enterobacteriaceae Infections/epidemiology , Health Facilities/trends , Hospitalization/statistics & numerical data , Infection Control/methods , California/epidemiology , Carbapenems/immunology , Centers for Disease Control and Prevention, U.S. , Computer Simulation , Cross Infection/prevention & control , Cross Infection/transmission , Drug Resistance, Bacterial , Enterobacteriaceae/drug effects , Enterobacteriaceae/immunology , Enterobacteriaceae Infections/prevention & control , Enterobacteriaceae Infections/transmission , Forecasting , Humans , Models, Theoretical , Population Surveillance/methods , Prevalence , United States/epidemiologyABSTRACT
BACKGROUND: Sepsis hospitalizations have increased dramatically in the last decade. It is unclear whether this represents an actual rise in sepsis illness or improved capture by coding. We evaluated the impact of Centers of Medicare and Medicaid Services (CMS) guidance after newly introduced sepsis codes and medical severity diagnosis-related group (MS-DRG) systems on sepsis trends. METHODS: In this retrospective cohort study of California hospitalizations from January 2000 to December 2010, sepsis was identified by International Classification of Diseases, Ninth Revision (ICD-9) coding (Dombrovskiy method). Sepsis-associated mortality rates were calculated. Logistic regression models evaluated variables associated with sepsis and mortality. Segmented regression time series analysis assessed changes in sepsis frequency for (1) baseline (January 2000 to September 2003); (2) post-CMS guidelines on sepsis coding (October 2003 to September 2007); and (3) after the introduction of MS-DRG (October 2007 to December 2010). RESULTS: Annual hospitalizations with sepsis diagnoses tripled within a decade, from 21.1 to 59.9 cases per 1000 admissions, with a 2.8- and 2.0-fold increase in severe and nonsevere sepsis, respectively, whereas annual admissions remained unchanged and sepsis-associated mortality decreased. Greatest increases were seen for severe sepsis present on admission (3.8-fold increase). Increases in sepsis were temporally correlated with CMS coding guidance and MS-DRG introduction after adjustment for comorbidity and other factors. CONCLUSIONS: Sepsis rate increases were associated with introduction of CMS-issued guidance for new sepsis ICD-9 coding and MS-DRGs. Coding artifact ("up-capture" of less severely ill septic patients) may be contributing to the apparent rise in sepsis incidence and decline in mortality. Epidemiologic trends based on administrative data should account for policy-related effects.
Subject(s)
Health Policy , Medicare , Sepsis/epidemiology , Adult , California/epidemiology , Comorbidity , Delivery of Health Care , Female , Hospitalization/statistics & numerical data , Humans , Incidence , International Classification of Diseases , Male , Middle Aged , Retrospective Studies , Sepsis/complications , Sepsis/diagnosis , Sepsis/mortality , Time Factors , United States/epidemiology , Young AdultABSTRACT
OBJECTIVE: To identify the genotypes of the blood sample whose blood grouping showed discrepancies and study the ABO alleles' molecular characteristics of the involved ancestry. METHODS: Blood samples were preliminary genotyped by PCR-SSP. Complete exon 6 and 7 in the ABO genes were amplified by PCR and the PCR products were directly sequenced and cloning sequenced to identify its genotype. RESULTS: Sequence analysis indicated that 3 samples of the family had an nt905A>G mutation in the B gene compared with ABO*B101. Combined with the serological results, the propositus could be typed as Bx02/O102. CONCLUSION: DNA sequencing analysis is able to identify the serological phenotype samples that forward and reverse group methods were incongruous.
Subject(s)
Alleles , ABO Blood-Group System , Base Sequence , Blood Grouping and Crossmatching , Exons , Genetic Testing , Genotype , Humans , Mutation , Phenotype , Polymerase Chain ReactionABSTRACT
OBJECTIVE: To assess the time-dependent exposure of California healthcare facilities to patients harboring methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, and Clostridium difficile infection (CDI) upon discharge from 1 hospital. METHODS: Retrospective multiple-cohort study of adults discharged from 1 hospital in 2005-2009, counting hospitals, nursing homes, cities, and counties in which carriers were readmitted, and comparing the number and length of stay of readmissions and the number of distinct readmission facilities among carriers versus noncarriers. RESULTS: We evaluated 45,772 inpatients including those with MRSA (N=1,198), VRE (N=547), ESBL (N=121), and CDI (N=300). Within 1 year of discharge, MRSA, VRE, and ESBL carriers exposed 137, 117, and 45 hospitals and 103, 83, and 37 nursing homes, generating 58,804, 33,486, and 15,508 total exposure-days, respectively. Within 90 days of discharge, CDI patients exposed 36 hospitals and 35 nursing homes, generating 7,318 total exposure-days. Compared with noncarriers, carriers had more readmissions to hospitals (MRSA:1.8 vs 0.9/patient; VRE: 2.6 vs 0.9; ESBL: 2.3 vs 0.9; CDI: 0.8 vs 0.4; all P<.001) and nursing homes (MRSA: 0.4 vs 0.1/patient; VRE: 0.7 vs 0.1; ESBL: 0.7 vs 0.1; CDI: 0.3 vs 0.1; all P<.001) and longer hospital readmissions (MRSA: 8.9 vs 7.3 days; VRE: 8.9 vs 7.4; ESBL: 9.6 vs 7.5; CDI: 12.3 vs 8.2; all P<.01). CONCLUSIONS: Patients harboring antibiotic-resistant pathogens rapidly expose numerous facilities during readmissions; regional containment strategies are needed.
Subject(s)
Cross Infection/epidemiology , Drug Resistance, Bacterial , Hospitals/statistics & numerical data , Nursing Homes/statistics & numerical data , Patient Readmission/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , California , Carrier State , Clostridium/isolation & purification , Cross Infection/prevention & control , Female , Humans , Klebsiella pneumoniae/isolation & purification , Length of Stay , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Patient Discharge , Retrospective Studies , Vancomycin-Resistant Enterococci/isolation & purification , Young AdultABSTRACT
BACKGROUND: Treatments for health care-associated infections (HAIs) caused by antibiotic-resistant bacteria and Clostridium difficile are limited, and some patients have developed untreatable infections. Evidence-supported interventions are available, but coordinated approaches to interrupt the spread of HAIs could have a greater impact on reversing the increasing incidence of these infections than independent facility-based program efforts. METHODS: Data from CDC's National Healthcare Safety Network and Emerging Infections Program were analyzed to project the number of health care-associated infections from antibiotic-resistant bacteria or C. difficile both with and without a large scale national intervention that would include interrupting transmission and improved antibiotic stewardship. As an example, the impact of reducing transmission of one antibiotic-resistant infection (carbapenem-resistant Enterobacteriaceae [CRE]) on cumulative prevalence and number of HAI transmission events within interconnected groups of health care facilities was modeled using two distinct approaches, a large scale and a smaller scale health care network. RESULTS: Immediate nationwide infection control and antibiotic stewardship interventions, over 5 years, could avert an estimated 619,000 HAIs resulting from CRE, multidrug-resistant Pseudomonas aeruginosa, invasive methicillin-resistant Staphylococcus aureus (MRSA), or C. difficile. Compared with independent efforts, a coordinated response to prevent CRE spread across a group of inter-connected health care facilities resulted in a cumulative 74% reduction in acquisitions over 5 years in a 10-facility network model, and 55% reduction over 15 years in a 102-facility network model. CONCLUSIONS: With effective action now, more than half a million antibiotic-resistant health care-associated infections could be prevented over 5 years. Models representing both large and small groups of interconnected health care facilities illustrate that a coordinated approach to interrupting transmission is more effective than historical independent facilitybased efforts. IMPLICATIONS FOR PUBLIC HEALTH: Public health-led coordinated prevention approaches have the potential to more completely address the emergence and dissemination of these antibiotic-resistant organisms and C. difficile than independent facility-based efforts.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/prevention & control , Cross Infection/prevention & control , Drug Resistance, Bacterial , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , Clostridioides difficile/drug effects , Cross Infection/epidemiology , Health Facilities , Humans , United States/epidemiologyABSTRACT
BACKGROUND: Reducing hospital readmissions, including preventable healthcare-associated infections, is a national priority. The proportion of readmissions due to infections is not well-understood. Better understanding of hospital risk factors for readmissions and infection-related readmissions may help optimize interventions to prevent readmissions. METHODS: Retrospective cohort study of California acute care hospitals and their patient populations discharged between 2009 and 2011. Demographics, comorbidities, and socioeconomic status were entered into a hierarchical generalized linear mixed model predicting all-cause and infection-related readmissions. Crude verses adjusted hospital rankings were compared using Cohen's kappa. RESULTS: We assessed 30-day readmission rates from 323 hospitals, accounting for 213 879 194 post-discharge person-days of follow-up. Infection-related readmissions represented 28% of all readmissions and were associated with discharging a high proportion of patients to skilled nursing facilities. Hospitals serving populations with high proportions of males, comorbidities, prolonged length of stay, and populations living in a federal poverty area, had higher all-cause and infection-related readmission rates. Academic hospitals had higher all-cause and infection-related readmission rates (odds ratio 1.24 and 1.15, respectively). When comparing adjusted vs crude hospital rankings for infection-related readmission rates, adjustment revealed 31% of hospitals changed performance category for infection-related readmissions. CONCLUSIONS: Infection-related readmissions accounted for nearly 30% of all-cause readmissions. High hospital infection-related readmissions were associated with serving a high proportion of patients with comorbidities, long lengths of stay, discharge to skilled nursing facility, and those living in federal poverty areas. Preventability of these infections needs to be assessed.
Subject(s)
Hospitalization/statistics & numerical data , Patient Readmission/statistics & numerical data , Poverty , California/epidemiology , Cohort Studies , Communicable Diseases/epidemiology , Comorbidity , Diagnosis-Related Groups , Hospitalization/economics , Humans , Length of Stay/economics , Length of Stay/statistics & numerical data , Odds Ratio , Patient Discharge/statistics & numerical data , Patient Readmission/economics , Poverty/statistics & numerical data , Retrospective Studies , Risk Factors , Skilled Nursing Facilities/standards , Skilled Nursing Facilities/statistics & numerical data , Socioeconomic FactorsABSTRACT
Across 366 California hospitals, we identified hospital-level characteristics predicting increased hospital-associated Clostridium difficile infection (HA-CDI) rates including more licensed beds, teaching and long-term acute care (LTAC) hospitals, and polymerase chain reaction testing. Adjustment for these characteristics impacted rankings in 24% of teaching hospitals, 13% of community hospitals, and 11% of LTAC hospitals.
Subject(s)
Clostridioides difficile , Cross Infection/epidemiology , Enterocolitis, Pseudomembranous/epidemiology , Hospitals/statistics & numerical data , California/epidemiology , Critical Care/statistics & numerical data , Female , Hospital Bed Capacity/statistics & numerical data , Hospitals/standards , Hospitals, Teaching/statistics & numerical data , Humans , Long-Term Care/statistics & numerical data , Male , Middle Aged , Polymerase Chain Reaction/statistics & numerical data , Retrospective Studies , Risk FactorsABSTRACT
We surveyed infection prevention programs in 16 hospitals for hospital-associated methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, extended-spectrum ß-lactamase, and multidrug-resistant Acinetobacter acquisition, as well as hospital-associated MRSA bacteremia and Clostridium difficile infection based on defining events as occurring >2 days versus >3 days after admission. The former resulted in significantly higher median rates, ranging from 6.76% to 45.07% higher.
Subject(s)
Acinetobacter Infections/diagnosis , Bacteremia/diagnosis , Carrier State/diagnosis , Clostridioides difficile , Cross Infection/diagnosis , Enterocolitis, Pseudomembranous/diagnosis , Practice Guidelines as Topic , Staphylococcal Infections/diagnosis , Acinetobacter , Acinetobacter Infections/epidemiology , Bacteremia/epidemiology , Bacteremia/microbiology , California , Carrier State/epidemiology , Carrier State/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Drug Resistance, Multiple, Bacterial , Enterocolitis, Pseudomembranous/epidemiology , Enterocolitis, Pseudomembranous/microbiology , Humans , Methicillin-Resistant Staphylococcus aureus , Prospective Studies , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Time Factors , Vancomycin-Resistant Enterococci , beta-Lactam ResistanceABSTRACT
BACKGROUND: States have established public reporting of hospital-associated (HA) infections-including those of methicillin-resistant Staphylococcus aureus (MRSA)-but do not account for hospital case mix or postdischarge events. OBJECTIVE: Identify facility-level characteristics associated with HA-MRSA infection admissions and create adjusted hospital rankings. METHODS: A retrospective cohort study of 2009-2010 California acute care hospitals. We defined HA-MRSA admissions as involving MRSA pneumonia or septicemia events arising during hospitalization or within 30 days after discharge. We used mandatory hospitalization and US Census data sets to generate hospital population characteristics by summarizing across admissions. Facility-level factors associated with hospitals' proportions of HA-MRSA infection admissions were identified using generalized linear models. Using state methodology, hospitals were categorized into 3 tiers of HA-MRSA infection prevention performance, using raw and adjusted values. RESULTS: Among 323 hospitals, a median of 16 HA-MRSA infections (range, 0-102) per 10,000 admissions was found. Hospitals serving a greater proportion of patients who had serious comorbidities, were from low-education zip codes, and were discharged to locations other than home were associated with higher HA-MRSA infection risk. Total concordance between all raw and adjusted hospital rankings was 0.45 (95% confidence interval, 0.40-0.51). Among 53 community hospitals in the poor-performance category, more than 20% moved into the average-performance category after adjustment. Similarly, among 71 hospitals in the superior-performance category, half moved into the average-performance category after adjustment. CONCLUSIONS: When adjusting for nonmodifiable facility characteristics and case mix, hospital rankings based on HA-MRSA infections substantially changed. Quality indicators for hospitals require adequate adjustment for patient population characteristics for valid interhospital performance comparisons.
Subject(s)
Cross Infection/epidemiology , Hospitals/standards , Methicillin-Resistant Staphylococcus aureus , Pneumonia, Staphylococcal/epidemiology , Sepsis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , California/epidemiology , Comorbidity , Cross Infection/prevention & control , Diagnosis-Related Groups , Female , Hospitals/statistics & numerical data , Humans , Male , Middle Aged , Pneumonia, Staphylococcal/microbiology , Pneumonia, Staphylococcal/prevention & control , Retrospective Studies , Risk Factors , Sepsis/microbiology , Sepsis/prevention & control , Young AdultABSTRACT
We assess the impact of revised International Classification of Diseases, Ninth Revision, codes on methicillin-resistant Staphylococcus aureus burden in California hospitals. Codes were rapidly adopted, demonstrating new capture of colonization and continued relatively stable capture of infections. Nevertheless, despite new colonization codes, coded data demonstrated poor retention between serial hospitalizations.
Subject(s)
Hospitals/statistics & numerical data , International Classification of Diseases , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/classification , Staphylococcal Infections/epidemiology , California/epidemiology , Humans , Retrospective StudiesABSTRACT
OBJECTIVE: To study the inducing effect of trichosanthin on the apoptosis of mouse prostatic cancer RM-1 cells and its mechanism. METHODS: MTT assay was used to identify the effect of trichosanthin on RM-1 cells in vitro. The cells apoptosis was detected by Hoechest 33258 fluorescent staining and flow cytometry. The levels of bax proteins were detected by western blot analysis as well as their apoptosis rate. RESULTS: The IC50 value of trichosanthin for RM-1 cell was 117.32 mg/L. Cell cycle was analysised by flow cytometry, trichosanthin induced an arrest in G0/G1 phase. Hoechest 33258 fluorescent staining showed typical nucleolus changes in apoptosis cells. Expression of bax was up-regulated at protein levels in a time-dependent manner. CONCLUSION: Trichosanthin can induce apoptosis in RM-1 cells. The induction of apoptosis is a very important mechanism of trichosanthin to inhibit prostatic cancer.