Nikolaos Andreatos

Discrepancy between financial disclosures of authors of clinical practice guidelines and reports by industry

Abstract There is a substantial effort to increase the accuracy of conflicts of interest (COI) reporting, and reduce the influence of COI between physicians and industry, especially as it relates to clinical practice guidelines. We used the newly implemented Open Payments dataset to evaluate the accuracy of COI disclosures of authors of clinical practice guidelines that were either newly published or revised within 2014 and were included in the National Guideline Clearinghouse (NGC) website (maintained by the U.S. Department of Health and Human Services). Authors were considered as having inaccurate COI disclosure if they had not reported all companies from which they had received funds >

The salivary microbiome is consistent between subjects and resistant to impacts of short-term hospitalization

5000 in the 12 months preceding the guidelines publication. We identified 223 guidelines that were either newly published (109/223; 48.9%) or revised (114/223; 51.1%) within 2014 and were included in the NGC website. Among the 1329 guideline authors with available Open Payments data, 523 received >

Extended-spectrum β-lactamase-producing Enterobacteriaceae colonisation in long-term care facilities: a systematic review and meta-analysis

5000 from at least 1 healthcare-associated entity. However, only 56 out of the 523 authors (10.7%) were found to have accurate COI disclosure. The percentage of authors with accurate COI disclosure in revised guidelines was significantly lower than in newly published guidelines (6.8% vs 14.3%; Pu200a<u200a0.01) and was also found to differ between specialties. Furthermore, authors were less likely to inaccurately disclose “research payments” (37/49, 75.5%) compared to “general payments” (488/559, 87.3%, Pu200a=u200a0.02) as well as “other/associated research funding” (430/506, 85.0%, Pu200a=u200a0.08). No statistically significant association was detected between funding amount and disclosure accuracy. The majority of guideline authors lacked significant COIs, but among authors that received significant funds from at least 1 healthcare-associated entity the frequency of accurate disclosure was low. These findings indicate that the current process of disclosing COIs may be suboptimal and a proactive approach should be adopted in order to minimize COI reporting discrepancies. Furthermore, every effort should be undertaken to ensure the completeness and accuracy of the data recorded in the Open Payments database.

The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

In recent years, a growing amount of research has begun to focus on the oral microbiome due to its links with health and systemic disease. The oral microbiome has numerous advantages that make it particularly useful for clinical studies, including non-invasive collection, temporal stability, and lower complexity relative to other niches, such as the gut. Despite recent discoveries made in this area, it is unknown how the oral microbiome responds to short-term hospitalization. Previous studies have demonstrated that the gut microbiome is extremely sensitive to short-term hospitalization and that these changes are associated with significant morbidity and mortality. Here, we present a comprehensive pipeline for reliable bedside collection, sequencing, and analysis of the human salivary microbiome. We also develop a novel oral-specific mock community for pipeline validation. Using our methodology, we analyzed the salivary microbiomes of patients before and during hospitalization or azithromycin treatment to profile impacts on this community. Our findings indicate that azithromycin alters the diversity and taxonomic composition of the salivary microbiome; however, we also found that short-term hospitalization does not impact the richness or structure of this community, suggesting that the oral cavity may be less susceptible to dysbiosis during short-term hospitalization.

Bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae among patients with malignancy: a systematic review and meta-analysis

The objectives of this study were to estimate the colonisation rate by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) among residents of long-term care facilities (LTCFs) and to identify pertinent risk factors. A systematic search of PubMed and EMBASE databases for studies published up to May 2016 that provided raw data for gastrointestinal colonisation by ESBL-PE among LTCF residents was performed. Twenty-three studies reporting data on 9775 screened subjects met the inclusion criteria. The pooled prevalence of ESBL-PE among LTCF residents was 18% [95% confidence interval (CI) 12-24%]. Risk factors for colonisation included recent antibiotic use (within 6 months) [odds ratio (OR)u2009=u20092.06, 95% CI 1.78-2.38], previous hospitalisation (within 2.5 years) (ORu2009=u20091.50, 95% CI 1.04-2.15), history of invasive procedures (within 2 years) (ORu2009=u20092.79, 95% CI 1.66-4.70), previous ESBL-PE colonisation or infection (ORu2009=u20096.77, 95% CI 1.33-34.62), history of urinary tract infection (ORu2009=u20092.66, 95% CI 1.76-4.01) and urinary catheter use (ORu2009=u20092.55, 95% CI 1.29-5.04). In conclusion, almost one in five LTCF residents is colonised with ESBL-PE, and colonised residents are more likely to have a history of recent antibiotic use or healthcare facility utilisation. Strict adherence to antimicrobial stewardship in LTCFs is needed to address these high resistance rates.

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

Abstract Background Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting. Methods We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016. Results Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009). Conclusions Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

The impact of HIV infection and socioeconomic factors on the incidence of gonorrhea: A county-level, US-wide analysis

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are an increasing cause of resistant infections among patients with malignancy. This study sought to estimate the prevalence of bloodstream infections (BSIs) caused by ESBL-PE in this population and to examine regional and temporal differences. The PubMed and EMBASE databases (to 30 April 2016) were searched to identify studies reporting ESBL-PE BSI rates among patients with malignancies. Of 593 non-duplicate reports, 22 studies providing data on 5650 BSI cases satisfied the inclusion criteria. Among all BSIs the pooled prevalence of ESBL-PE was 11% (95% CI 8-15%) and among Gram-negative BSIs it was 21% (95% CI 16-27%). Among patients with haematological malignancies, the pooled ESBL-PE prevalence was 11% (95% CI 8-15%), whereas no studies providing specific data on patients with solid tumours were identified. Stratifying per geographic region, the pooled prevalence was 7% each in Europe (95% CI 5-11%), the Eastern Mediterranean region (95% CI 4-11%) and South America (95% CI 2-14%), 10% in the Western Pacific region (95% CI 4-19%) and 30% in Southeast Asia (95% CI 18-44%). Importantly, there was a 7.1% annual increase in the ESBL-PE incidence (Pu2009=u20090.004). Overall, ca. 1 in 10 BSIs in patients with malignancy is caused by ESBL-PE and in some areas this rate can be as high as 1 in 3 cases. Additionally, the incidence of these resistant infections is rising. These findings should be considered when selecting empirical antimicrobial therapy and should prompt strict adherence to antimicrobial stewardship.

Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis

SUMMARY 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

The impact of antibiotic prescription rates on the incidence of MRSA bloodstream infections: a county-level, U.S.-wide analysis

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, −

Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and Clostridium difficile

29,205/quality-adjusted life year). BC-GN with an ASP (ICER, −