The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship.

Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, -$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, -$23,587/quality-adjusted life year), PCR with an ASP (ICER, -$19,833/quality-adjusted life year), and PCR without an ASP (ICER, -$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.

The Cost-effectiveness of Antimicrobial Lock Solutions for the Prevention of Central Line-Associated Bloodstream Infections.

Background: Antimicrobial lock solutions are a low-cost strategy that can reduce the incidence of central line-associated bloodstream infection (CLABSI). The aim of this study was to evaluate the cost-effectiveness of antimicrobial locks for the prevention of CLABSI. Methods: We constructed a decision-analytic model comparing antimicrobial lock solutions to heparin locks for the prevention of CLABSI in 3 settings: hemodialysis, cancer treatment, and home parenteral nutrition. Cost-effectiveness was determined by calculating CLABSIs prevented and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results: In probabilistic analysis, at a willingness to pay of $50000, antimicrobial lock solutions had a 96.24% chance of being cost-effective, compared with heparin locks in the hemodialysis setting, an 88.00% chance in the cancer treatment setting, and a 92.73% chance in the home parenteral nutrition setting. In base-case analysis, antimicrobial lock solutions resulted in savings of $68721.03 for the hemodialysis setting, $85061.41 for the cancer setting, and $78513.83 for the home parenteral nutrition setting per CLABSI episode prevented. Conclusions: In 3 distinct and clinically important settings (hemodialysis, cancer treatment, and home parenteral nutrition), antimicrobial lock solutions are an effective strategy for the prevention of CLABSI, and their use can result in significant healthcare savings.

Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations.

Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls. We found that SS patients at high risk for lymphoma and those with established lymphoma display high serum cf-DNA levels, substantial extranuclear DNA accumulations in PBMC and SG tissues, a unique NLRP3 inflammasome gene signature in PBMC, and significantly increased serum IL-18 and ASC levels. In these patients, the circulating monocytes manifested NLRP3 inflammasome activation and increased response to NLRP3 stimuli, whereas SG-infiltrating macrophages exhibited signs of NLRP3 activation and pyroptosis. Cell-free nucleic acids isolated from patients' sera competently primed the activation of both NLRP3 and AIM2 inflammasomes in healthy monocytes. SS patients also manifested diminished DNaseI activity in serum and DNaseII expression in PBMC, which inversely correlated with indices of inflammasome activation. DNaseII gene-silencing in healthy monocytes led to cytoplasmic DNA deposition and activation of inflammasome-related genes and of caspase1. Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.

Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.

PURPOSE: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. METHODS: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. RESULTS: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). CONCLUSION: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

FcγRIIa-H131R variant is associated with inferior response in diffuse large B cell lymphoma: A meta-analysis of genetic risk.

PURPOSE: Low-affinity variants FcγRIIIa-V158F and FcγRIIa- H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response. METHODS: We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORG). PubMed and EMBASE search (up to July 2014) yielded five pertinent studies. RESULTS: FcγRIIa-H131R was associated with an inferior response to treatment (ORG 0.67; 95%CI 0.46-0.97) and an additive mode of inheritance, with the genetic risk of heterozygotes assigned in the middle between high affinity (H/H) and lower affinity (R/R) genotypes. This effect was unrelated to risk stratification, as no association was documented for FcγRIIa-H131R variant with the international prognostic index (IPI) (ORG 1.02; 95%CI 0.79-1.31 for IPI 3-5 over 0-2). FcγRIIIa-V158F had no impact on treatment response but linkage disequilibrium and defective antibody-dependent cell-mediated cytotoxicity may have affected the outcome. CONCLUSION: FcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.

Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis.

OBJECTIVES: It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied. METHODS: We searched PubMed and EMBASE databases up to 20 June 2014, using the term "difficile". Our primary outcomes of interest included the prevalence of isolation of toxinogenic C. difficile or its toxins from asymptomatic patients on hospital admission through stool or rectal swab testing and the risk of ensuing infection among colonized and noncolonized patients. Data on previous hospitalization, antibiotic, and proton pump inhibitor (PPI) use and prior CDIs among colonized and noncolonized patients were also extracted. RESULTS: Nineteen out of 26,081 studies on 8,725 patients were included. The pooled prevalence of toxinogenic C. difficile colonization was 8.1% (95% confidence interval (CI) 5.7-11.1%), with an increasing trend over time (P=0.003), and 10.0% (95% CI 7.1-13.4%) among North American studies. Patients colonized upon hospital admission had a 5.9 times higher risk of subsequent CDIs compared with noncolonized patients (relative risk (RR) 5.86; 95% CI 4.21-8.16). The risk of CDI for colonized patients was 21.8% (95% CI 7.9-40.1%), which was significantly higher than that of noncolonized patients (3.4%; 95% CI 1.5-6.0%; P=0.03), with an attributable risk of 18.4%. History of hospitalization during the previous 3 months was associated with a higher risk of colonization (RR 1.63; 95% CI 1.13-2.34), as opposed to previous antibiotic (RR 1.07; 95% CI 0.75-1.53) and PPI use (RR 1.44; 95% CI 0.94-2.23), as well as history of CDI (RR 1.45; 95% CI 0.66-3.18) that had no impact. CONCLUSIONS: Over 8% of admitted patients are carriers of toxinogenic C. difficile with an almost 6 times higher risk of infection. These findings update current knowledge regarding the contribution of colonization in CDI epidemiology and stress the importance of preventive measures toward colonized patients.

Methicillin-resistant Staphylococcus aureus prevention strategies in the ICU: a clinical decision analysis*.

OBJECTIVES: ICUs are a major reservoir of methicillin-resistant Staphylococcus aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant Staphylococcus aureus prevention policies. DESIGN AND INTERVENTIONS: We evaluated three up-to-date methicillin-resistant Staphylococcus aureus prevention policies, namely, 1) nasal screening and contact precautions of methicillin-resistant Staphylococcus aureus-positive patients; 2) nasal screening, contact precautions, and decolonization (targeted decolonization) of methicillin-resistant Staphylococcus aureus carriers; and 3) universal decolonization without screening. We implemented a decision-analytic model with deterministic and probabilistic analyses. Methicillin-resistant Staphylococcus aureus infections averted, quality-adjusted life years gained, and incremental cost-effectiveness ratios were calculated. Cost-effectiveness planes and acceptability curves were plotted for various willingness-to-pay thresholds to address uncertainty. MEASUREMENTS AND MAIN RESULTS: At base-case scenario, universal decolonization was the dominant strategy; it averted 1.31% and 1.59% of methicillin-resistant Staphylococcus aureus infections over targeted decolonization and screening and contact precautions, respectively, and saved $16,203/quality-adjusted life year over targeted decolonization and 14,562/quality-adjusted life year over screening and contact precautions. Results were robust in sensitivity analysis for a wide range of input variables. In probabilistic analysis, universal decolonization increased quality-adjusted life years by 1.06% (95% CI, 1.02-1.09) over targeted decolonization and by 1.29% (95% CI, 1.24-1.33) over screening and contact precautions; universal decolonization resulted in average savings of $172 (95% CI, $168-$175) and $189 (95% CI, $185-$193) over targeted decolonization and screening and contact precautions, respectively. With willingness-to-pay threshold per quality-adjusted life year gained ranging from $0 to $50,000, universal decolonization was dominant over targeted decolonization in 67.5-75.4% and dominant over screening and contact precautions in 66.0-75.4%. CONCLUSIONS: In the ICU setting, universal decolonization outperforms the other two strategies and is likely to be cost-effective even at low willingness-to-pay thresholds. Assuming 700 annual ICU admissions in an average 12-bed ICU, the projected annual savings reach $129,500 to $135,100.

Vancomycin-resistant enterococci colonization among dialysis patients: a meta-analysis of prevalence, risk factors, and significance.

BACKGROUND: Vancomycin-resistant enterococci (VRE) have become important nosocomial pathogens causing outbreaks worldwide. Patients undergoing dialysis represent a vulnerable population due to their comorbid conditions, frequent use of antibacterial agents, and frequent contact with health care settings. STUDY DESIGN: Systematic review and meta-analysis of cross-sectional studies of screening for VRE colonization. SETTING & POPULATION: Patients receiving long-term dialysis treatment. SELECTION CRITERIA FOR STUDIES: We performed a systematic literature search of PubMed and EMBASE databases to identify studies performing screening for VRE colonization among dialysis patients. PREDICTOR: Region, recent use of vancomycin or other antibiotics, previous hospitalization. OUTCOMES: (1) VRE colonization and (2) rate of VRE infection among colonized and noncolonized individuals. Relative effects were expressed as ORs and 95% CIs. RESULTS: We identified 23 studies that fulfilled the inclusion criteria and provided data for 4,842 dialysis patients from 100 dialysis centers. The pooled prevalence of VRE colonization was 6.2% (95% CI, 2.8%-10.8%), with significant variability between centers. The corresponding number for North American centers was 5.2% (95% CI, 2.8%-8.2%). Recent use of any antibiotic (OR, 3.62; 95% CI, 1.22-10.75), particularly vancomycin (OR, 5.15; 95% CI, 1.56-17.02), but also use of antibiotics other than vancomycin (OR, 2.92; 95% CI, 0.99-8.55) and recent hospitalization (OR, 4.55; 95% CI, 1.93-10.74) significantly increased the possibility of a VRE-positive surveillance culture. Colonized patients had a significantly higher risk of VRE infection (OR, 21.62; 95% CI, 5.33-87.69) than their noncolonized counterparts. LIMITATIONS: In 19 of 23 studies, a low percentage of dialysis patients (<80%) consented to participate in the screening procedure. 4 of 8 studies in which patients were followed up for more than 1 month reported VRE infections and only 5 of 23 studies provided extractable data for antibiotic consumption prior to screening. CONCLUSIONS: VRE colonization is prevalent in dialysis centers. Previous antibiotic use, in particular vancomycin, and recent hospitalization are important predicting factors of colonization, whereas the risk of VRE infection is significantly higher for colonized patients.

Meta-analysis of methicillin-resistant Staphylococcus aureus colonization and risk of infection in dialysis patients.

Patients undergoing dialysis are particularly vulnerable to methicillin-resistant Staphylococcus aureus (MRSA) infections. We performed a meta-analysis of published studies to estimate the prevalence of MRSA colonization in dialysis patients, time trends, and long-term risk of subsequent MRSA infections. Our search of the PubMed and Embase databases returned 5743 nonduplicate citations, from which we identified 38 relevant studies that included data on 5596 dialysis patients. The estimated prevalence of MRSA colonization was 6.2% (95% confidence interval [95% CI], 4.2% to 8.5%). The prevalence increased over time but remained stable after 2000. Stratification of patients according to dialysis modality and setting revealed that 7.2% (95% CI, 4.9% to 9.9%) of patients on hemodialysis were colonized with MRSA compared with 1.3% (95% CI, 0.5% to 2.4%) of patients on peritoneal dialysis (P=0.01), and that a statistically significant difference existed in the percentage of colonized inpatients and outpatients (14.2% [95% CI, 8.0% to 21.8%] versus 5.4% [95% CI, 3.5% to 7.7%], respectively; P=0.04). Notably, the risk of developing MRSA infections increased among colonized hemodialysis patients compared with noncolonized patients (relative risk, 11.5 [95% CI, 4.7 to 28.0]). The long-term (6-20 months) probability of developing a MRSA infection was 19% among colonized hemodialysis patients compared with only 2% among noncolonized patients. In summary, 6.2% of dialysis patients are MRSA colonized, and the average prevalence of colonization has remained stable since 2000. Colonization in hemodialysis patients is associated with increased risk of MRSA infection.

Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis.

OBJECTIVE: Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections. METHODS: We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs. RESULTS: A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17-2.74; I(2) = 3%), resulting in 1.7 excess infections per 1000 patients treated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2) = 0), and viral (OR, 1.91; 95% CI, 1.02-3.58; I(2) = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46-3.72), invasive fungal infections (2.85; .68-11.91), P. jirovecii pneumonia (1.77; .42-7.47), varicella-zoster virus (1.51; .71-3.22), as well as overall mortality attributed to OIs (1.91; .29-12.64). CONCLUSIONS: Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents.

Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization in HIV infection: a meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) have increased risk for MRSA infection. We conducted a meta-analysis of published studies to estimate the prevalence of MRSA colonization in this population. METHODS: We performed a systematic literature review and meta-analysis. The PubMed and Embase databases were searched and studies reporting prevalence of MRSA colonization among HIV-infected individuals were included. RESULTS: Among 7940 citations, 32 studies reporting data on 6558 HIV-infected individuals were considered eligible for our meta-analysis. We found that 6.9% (95% confidence interval [CI], 4.8-9.3) of individuals with HIV infection are MRSA carriers, with the corresponding figure across North American studies being 8.8% (95% CI, 6.0-12.2). History of hospitalization during the previous 12 months was associated with a 3.1 times higher risk of MRSA colonization (risk ratio [RR], 3.11 [95% CI, 1.62-5.98]). Previous or current incarceration was also associated with a higher risk for carriage (RR, 1.77 [95% CI, 1.26-2.48]). Current antiretroviral therapy or use of trimethoprim-sulfamethoxazole did not impact the risk of MRSA carriage (RR, 1.02 [95% CI, .64-1.63] and 1.45 [95% CI, .69-3.03], respectively). Extranasal screening increased the detection of MRSA colonization by at least 31.6% (95% CI, 15.8-50.0). The added yield from groin screening was 19.3% (95% CI, 11.5-28.5), from perirectal screening 18.5% (95% CI, 7.4-33.2), and from throat cultures 17.5% (95% CI, 12.0-24). CONCLUSIONS: Individuals with HIV infection constitute a highly vulnerable population for MRSA colonization, and prior exposure to hospital or incarceration are significant factors. Nasal screening alone will underestimate the rate of colonization by at least one-third.

Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials.

BACKGROUND: Antimicrobial lock solutions may be an effective strategy to prevent catheter-associated infections. However, there remains concern about their efficacy and safety. METHODS: To investigate the efficacy of antimicrobial lock therapy to prevent central line-associated bloodstream infections (CLABSIs), we performed a systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, from the earliest date up to 31 December 2013. Studies were eligible if they were randomized controlled trials comparing antimicrobial lock solutions to heparin and if they provided an appropriate definition of infection. RESULTS: The 23 included studies reported data on 2896 patients, who were predominantly adult patients undergoing hemodialysis (16/23 studies), but also adult and pediatric oncology patients, critically ill neonates, and patients receiving total parenteral nutrition. The use of antimicrobial lock solutions led to a 69% reduction in CLABSI rate (relative risk [RR], 0.31; 95% confidence interval [CI], .24-.40) and a 32% reduction in the rate of exit site infections (RR, 0.68; 95% CI, .49-.95) compared with heparin, without significantly affecting catheter failure due to noninfectious complications (RR, 0.83; 95% CI, .65-1.06). All-cause mortality was not different between the groups (RR, 0.84; 95% CI .64-1.12). Neither the type of antimicrobial solution nor the population studied, affected the relative reduction in CLABSIs, which also remained significant among studies reporting baseline infection rates of <1.15 per 1000 catheter-days, and studies providing data for catheter-related bloodstream infections. Publication and selective reporting bias are a concern in our study and should be acknowledged. CONCLUSIONS: Antimicrobial lock solutions are effective in reducing risk of CLABSI, and this effect appears to be additive to traditional prevention measures.

Clostridium difficile infection in the hematopoietic unit: a meta-analysis of published studies.

Hematopoietic stem cell transplant (HSCT) recipients are at high risk of contracting Clostridium difficile infection (CDI). We systematically searched the PubMed and EMBASE databases through March 2014 and performed a random-effects meta-analysis to estimate the prevalence and trends of CDI over time. Among 48 eligible articles that included 12,025 patients at risk, we estimated that 7.9% (95% confidence interval [CI], 6.5% to 9.5%) of HSCT patients are diagnosed with CDI during the peri-transplantation and late post-transplantation periods, an estimation that is relatively consistent across studies (τ(2) = .032). Prevalence of CDI is significantly higher among the 5120 allogeneic patients (9.3% [95% CI, 7.0% to 11.9%]), compared with the 4665 autologous patients (5.2% [95% CI, 3.8% to 6.9%]) (P = .02), and as many as 1 of 10 allogeneic transplant recipients are expected to be diagnosed with CDI compared with 1 of 20 autologous transplantation patients. However, this difference did not reach statistical significance when stratified data from the same centers were examined (P = .11). Importantly, we found an increasing trend of CDI diagnosis both worldwide (P = .02) and across studies conducted in North America (P = .03) over the last 34 years. Notably, studies with a follow-up period that extended through the late post-transplantation period (after day +100) had a similar prevalence of CDI as those that followed patients only during the peri-transplantation period (up to day +100) (P = .94). In summary, CDI is common in the hematopoietic transplantation setting and the majority of infections occur in the peri-transplantation period. The prevalence is almost 9-times higher than that reported among all hospital stays, with an increasing trend over time.

PCR in diagnosis of invasive aspergillosis: a meta-analysis of diagnostic performance.

Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality rate that affects high-risk groups such as patients with neutropenia and hematologic malignancies. We performed a bivariate meta-analysis of diagnostic data for an Aspergillus sp. PCR assay with blood specimens from high-risk hematology patients. We included all studies involving human subjects that assessed the performance of any PCR assay for invasive aspergillosis in whole blood or serum and that used the European Organization for the treatment of Cancer/Mycoses Study Group criteria as a reference standard. Three investigators independently searched the literature for eligible studies and extracted the data. Out of a total of 37 studies, 25 met strict quality criteria and were included in our evidence synthesis. Twenty-five studies with 2,595 patients were analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays was moderate, with a sensitivity and specificity of 84% (95% confidence interval [CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a positive or negative result is unable, on its own, to confirm or exclude a suspected infection. The performance of a PCR assay of serum was not significantly different from that of whole blood. Notably, at least two positive PCR test results were found to have a specificity of 95% and a sensitivity of 64% for invasive infection, achieving a high positive likelihood ratio of 12.8. Importantly, the European Aspergillus PCR Initiative (EAPCRI) recommendations improved the performance of the PCR even further when at least two positive specimens were used to define PCR positivity. In conclusion, two positive PCR results should be considered highly indicative of an active Aspergillus sp. infection. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance.

The prevalence and significance of methicillin-resistant Staphylococcus aureus colonization at admission in the general ICU Setting: a meta-analysis of published studies.

OBJECTIVE: To estimate the prevalence and significance of nasal methicillin-resistant Staphylococcus aureus colonization in the ICU and its predictive value for development of methicillin-resistant S. aureus infection. DATA SOURCES: MEDLINE and EMBASE and reference lists of all eligible articles. STUDY SELECTION: Studies providing raw data on nasal methicillin-resistant S. aureus colonization at ICU admission, published up to February 2013. Analyses were restricted in the general ICU setting. Medical, surgical, and interdisciplinary ICUs were eligible. ICU studies referring solely on highly specialized ICUs populations and reports on methicillin-resistant S. aureus outbreaks were excluded. DATA EXTRACTION: Two authors independently assessed study eligibility and extrapolated data in a blinded fashion. The two outcomes of interest were the prevalence estimate of methicillin-resistant S. aureus nasal colonization at admission in the ICU and the sensitivity/specificity of colonization in predicting methicillin-resistant S. aureus-associated infections. DATA SYNTHESIS: Meta-analysis, using a random-effect model, and meta-regression were performed. Pooled data extracted from 63,740 evaluable ICU patients provided an estimated prevalence of methicillin-resistant S. aureus nasal colonization at admission of 7.0% (95% CI, 5.8-8.3). Prevalence was higher for North American studies (8.9%; 95% CI, 7.1-10.7) and for patients screened using polymerase chain reaction (14.0%; 95% CI, 9.6-19). A significant per year increase in methicillin-resistant S. aureus colonization was also noted. In 17,738 evaluable patients, methicillin-resistant S. aureus infections (4.1%; 95% CI, 2.0-6.8) developed in 589 patients. The relative risk for colonized patients was 8.33 (95% CI, 3.61-19.20). Methicillin-resistant S. aureus nasal carriage had a high specificity (0.96; 95% CI, 0.90-0.98) but low sensitivity (0.32; 95% CI, 0.20-0.48) to predict methicillin-resistant S. aureus-associated infections, with corresponding positive and negative predictive values at 0.25 (95% CI, 0.11-0.39) and 0.97 (95% CI, 0.83-1.00), respectively. CONCLUSIONS: Among ICU patients, 5.8-8.3% of patients are colonized by methicillin-resistant S. aureus at admission, with a significant upward trend. Methicillin-resistant S. aureus colonization is associated with a more than eight-fold increase in the risk of associated infections during ICU stay, and methicillin-resistant S. aureus infection develops in one fourth of patients who are colonized with methicillin-resistant S. aureus at admission to the ICU.

CT-guided radiofrequency tumor ablation in children.

BACKGROUND: Image-guided radiofrequency ablation is a well-accepted technique of interventional oncology in adults. OBJECTIVE: To evaluate the efficacy and safety of CT-guided radiofrequency ablation as a minimally invasive treatment for metastatic neoplasms in children. MATERIALS AND METHODS: A total of 15 radiofrequency ablation sessions were performed in 12 children and young adults (median age 9.5; range 5-18 years) with metastatic malignancies. Seven children and young adults had secondary hepatic lesions, three had pulmonary and two had bone lesions. Radiofrequency ablation was performed under conscious sedation. RESULTS: The median lesion size was 1.7 cm (range 1.3-2.8 cm). The median time for ablation was 8 min (range 7-10 min). Radiofrequency procedures were technically successful in all tumors. Postablation imaging immediately after, and 1 month and 3 months after radiofrequency ablation showed total necrosis in all patients. At 6-month follow-up, three patients (all with lesion size >2 cm) had local recurrence and underwent a second radiofrequency ablation session. At 2-year follow-up no patient had recurrence of the treated tumor. Post-ablation syndrome occurred in four children. No major complication occurred. CONCLUSION: CT-guided radiofrequency tumor ablation was safe and efficient for palliative treatment in our cohort of patients.

Public interest trends for COVID-19 and pandemic trajectory: A time-series analysis of US state-level data.

Google Trends provides spatiotemporal data for user-specific terms scaled from less than 1 (lowest relative popularity) to 100 (highest relative popularity) as a proxy for the public interest. Here we use US state-level data for COVID-19 to examine popularity trends during the pandemic evolution. We used "coronavirus" and "covid" search terms and set the period up from January 1st, 2020, to November 12, 2022. We measured the agreement on web rankings between states using the nonparametric Kendall's W (0 for no concordance to 1 for perfect agreement). We compiled state-level weekly data on COVID-19 incidence and mortality and scaled state curves from 0 to 100 through a min-max normalization process. We used a dynamic time-warping algorithm to calculate similarities between the popularity, mortality, and incidence of COVID-19. The methodology is a pattern recognition process between time series by distance optimization. The similarity was mapped from 0 to 1, with 1 indicating perfect similarity and 0 indicating no similarity. The peak in popularity was in March 2020, succeeded by a decline and a prolonged period of fluctuation around 20%. Public interest rose briefly at the end of 2021, to fall to a low activity of around 10%. This pattern was remarkably consistent across states (Kendal's W 0.94, p < 0.001). Web search trends were an impression of contagion growth: Overall, popularity-mortality trajectories yielded higher similarity indices (median 0.78; interquartile range 0.75-0.82) compared to popularity-incidence trajectories (median 0.74; interquartile range 0.72-0.76, Wilcoxon's exact p<0.001). The popularity-mortality trajectories had a very strong similarity (>0.80) in 19/51 (37%) regions, as opposed to only 4/51 (8%) for popularity-incidence trajectories. State-level data show a fading public concern about COVID-19, and web-search popularity patterns may reflect the COVID-19 trajectory in terms of cases and mortality.

Risk factors for invasive fungal disease after allogeneic hematopoietic stem cell transplantation: a single center experience.

Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34(+) cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 10(6) cells/kg increase in CD34(+) cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed.

Interleukin-6 polymorphisms and hematologic malignancy: a re-appraisal of evidence from genetic association studies.

CONTEXT: Interleukin-6 (IL-6) is implicated in the pathophysiology of hematologic neoplasia. OBJECTIVE: To review the role of IL-6 single nucleotide polymorphisms (SNPs) in hematologic neoplasia. METHODS: PubMed and EMBASE search of genetic association studies. Effects were summarized using the model-free generalized odds ratio (ORG), and the mode of inheritance was estimated for significant associations. RESULTS: Seventeen articles provided data on 20 distinct SNPs. The IL-6 receptor rs8192284 was associated with an increased risk of hematologic malignancy (combined ORG 1.42, 95%CI 1.03-1.96), including multiple myeloma (ORG 1.39, 95%CI 0.99-1.95). The IL-6 promoter rs1800795 conferred protection against young adult Hodgkin's disease (ORG 0.68, 95%CI 0.48-0.95). Significant single-study effects for four other SNPs-disease associations were estimated. The IL-6 promoter rs1800795 and rs1800797 were not associated with overall susceptibility to non-Hodgkin's lymphomas. CONCLUSIONS: There is accumulating evidence that the IL-6 promoter, receptor and signal transducer SNPs can modify disease susceptibility.

Indications for bone marrow examination in autoimmune disorders with concurrent haematologic alterations.

OBJECTIVES: The aim of this study was to evaluate the aetiology of 'unexplained' cytopenias in patients with autoimmune disorders, as well as to identify parameters that should alert clinicians to the need for bone marrow examination. METHODS: During the study period (2005-2010), 110 consecutive patients with an underlying systemic autoimmune disease, excluding Sjogren's syndrome, were referred for haematological consultation and bone marrow examination, due to cytopenias without evident cause including blood loss, haemolysis, nutritional deficiencies and haemoglobin disorders. RESULTS: Systemic lupus erythaematosus was the most frequent underlying condition (38/110, 34.5%), and anaemia (haemoglobin<12gr/dl) the most common haematologic abnormality (81/110, 74%). Prior to evaluation, more than half of the patients received cytotoxic or immunosuppressive drugs, with methotrexate being the most commonly administrated agent (29/110, 26.4%). Evaluation was informative in 31 (28.2%) of the cases. Twenty-four (21.8%) cases of haematologic clonal disease were diagnosed; 11 myelodysplastic syndromes, 6 lymphoproliferative disorders, 6 plasma cell dyscrasias and one myeloproliferative neoplasm. Seven cases (6.4%) with bone marrow toxicity were also noted. Male gender, serum iron >90 µg/dl, mean corpuscular volume (MCV) >90fl, and serum monoclonal band were significant predictors of specific diagnosis including clonal haematologic disorder or bone marrow toxicity. All other correlations were insignificant. CONCLUSIONS: Clonal haematologic disorders and toxicity are frequent findings in patients with autoimmunity referred for haematologic consultation, owing to otherwise unexplained cytopenias. Patients with high serum iron, high MCV and presence of serum monoclonal band should undergo bone marrow examination to exclude haematologic malignancy or bone marrow toxicity.