bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clostridium difficile (CD) Action Team (CDAT): An Intervention to Improve Care for Patients with a Positive CD PCR
Authors: Markou Theodore , Fabre Valeria , Dzintars Kathryn , Avdic Edina , Shulder Stephanie , Andonian Jennifer , Rock Clare , Cosgrove Sara E 
Published: October 2017

Abstract

Background
CD infections (CDI) may be viewed by healthcare workers (HCW) as an unpreventable consequence of antibiotics (abx). The purpose of CDAT was to use patient cases in real time to educate HCW on CD diagnostic, treatment and prevention practices including appropriate abx and proton-pump inhibitors (PPI) use.

Methods
From 7/17/16 to 5/6/17, Johns Hopkins abx stewardship team reviewed positive CD PCRs in inpatient to determine whether they had CDI or colonization (no diarrhea or an alternate cause) and if prevention and management was optimal. Included in this time are 2 surveillance periods (SP) (SP1: 7/17–9/27/16 and SP2: 12/18/16–3/30/17). During SP1, there was no contact with HCW. SP2 followed the intervention, and allowed assessment of sustained practice changes. During the intervention periods (IP) (IP1: 10/9–12/17/16 and IP2: 3/31–5/6/17), teaching points for optimizing care for each case were shared and discussed in person with the HCW team, including prescribers and nursing. Compliance with recommendations at 48 hours was assessed. Chi-square test was used to compare sub-optimal management for each variable in different time periods.

Results
We assessed 217 cases in the SPs and 96 cases in the IPs. 75 of 96 cases reviewed in the IPs required intervention. CDAT spoke to 74 teams, which led to a change in the care of patients in 49 cases (65%). Compliance with recommendations were as follows: 1) stop or modify CDI therapy, 53%, (39 cases); 2) stop PPI therapy, 52% (15 cases); 3) stop laxatives, 53% (9 cases); 4) stop or modify non-CDI abx, 46% (16 cases); and 5) improve BM documentation, 58% (11 cases). The Figure shows proportions of patients with suboptimal CD management without (SPs) or before (IPs) CDAT intervention in each period. There were no changes in practice between the SP1 and IP1. Between the SP1 and IP2, significant improvement in BM documentation was seen (P = 0.007). No differences were observed for other variables, although there was a trend towards improved CD therapy (P = 0.09).

Conclusion
Overall, prescribers did not independently change practice as a result of daily contact with CDAT; however, they were responsive to CDAT recommendations. BM documentation, the only nursing intervention, improved significantly.

Disclosures
All authors: No reported disclosures.
Know When to Test: Optimizing Diagnostic Practices for Clostridium difficile Infection (CDI) Among Patients at a Tertiary-Care Cancer Center
Authors: Aslam Anoshé , Eagan Janet , Kaplan Janice , Robilotti Elizabeth , McMillen Tracy , Kamalska-Cyganik Monika , Kelson Suzanne , Nevrekar Reshma , Narain Wazim , Stetson Peter , Kamboj Mini , Babady N Esther 
Published: October 2017

Abstract

Background
Polymerase chain reaction (PCR) based diagnostic testing for the detection of toxigenic Clostridium difficile infection (CDI) does not distinguish between carriers and patients with true CDI. As a result, CDI is over-diagnosed in hospitalized patients with diarrhea. Unnecessary testing generates false positives and several downstream sequelae.
Aim: The aim of this study was to reduce unnecessary testing for CDI through an electronic alert, targeted education, and implementation of evidence-based laboratory testing policy.

Methods
In order to quickly identify laxative induced diarrhea and avoid CDI testing, an electronic alert was created in the electronic medical record (EMR) system. The alert was built on a logic that identified patients who had received laxatives within 48 hours of a CDI PCR test order. The alert additionally provided the rationale for avoiding testing in patients on laxatives and guidance on appropriate testing for CDI. The following steps were taken simultaneously to complement these efforts: 1) Infection Control conducted hospital-wide education for licensed independent practitioners on a CDI testing algorithm 2) Laboratory based policy was instated to reject all formed stools (Bristol Stool Chart types 1 through 4) for CDI testing.

Results
In the 6 month pre-intervention period, there were 29 CDI tests per 1000 patient-days. In the post-intervention period, CDI tests decreased to 19 per 1000 patient-days, a 35% decrease (P &lt; 0.0001). The decline in testing has been sustained for 7 months. The following observations were also made: 1) HAI rate reduction of 28%; 2) decrease in oral vancomycin use.

Conclusion
Decreasing inappropriate testing has several distinct advantages, including reducing excessive and unnecessary antibiotic use, avoiding misclassification of carriers as CDI cases, normalizing healthcare-associated CDI rates, and diminishing healthcare costs associated with preventable tests. Laboratories that use PCR only testing for CDI diagnosis should follow stringent policies to ensure that only patients with high pretest probability are tested. EMR systems are a useful and effective resource to achieve this for patients with laxative induced diarrhea.

Disclosures
All authors: No reported disclosures.
Enzyme Immunoassay for C. difficile Toxin Reduces Lab ID Events but Fails to Detect Clinically Significant C. difficile Infection
Authors: Ridgway Jessica P , Murillo Cynthia , Marrs Rachel , Garcia-Houchins Sylvia , Harper Clinitka , Bartlett Allison H , Landon Emily 
Published: October 2017

Abstract

Background
The National Health Safety Network (NHSN) requires reporting of Lab ID events for C. difficile infection (CDI) including all positive clinical tests after day three of hospitalization. Nucleic acid amplification tests (NAAT) that detect genes for toxins A and/or B may be overly sensitive, in some cases detecting C. difficile colonization. Some have advocated for two-stage testing, with positive NAAT tests followed by confirmatory enzyme immunoassay (EIA) to detect the presence of toxin and minimize the downside of false positives (i.e. additional NHSN reports or overuse of antibiotics). We aimed to better understand clinical characteristics of patients with positive NAAT and/or EIA tests.

Methods
Our hospital uses Xpert C. difficile assay (Cepheid), a NAAT method utilizing polymerase chain reaction (PCR), to diagnose CDI on unformed stool only. As part of a 6 month quality initiative, we pilot tested the C.DIFF QUIK CHEK COMPLETE® test (Alere), an EIA that tests for C. difficileantigen (Ag) and toxin, on all specimens that tested positive by NAAT. We abstracted clinical data from the medical record for a subset of patients who underwent EIA testing.

Results
Over 6 months, 294 patients had a positive test by NAAT. Of these, 258 (87.8%) underwent EIA testing. 67 (26.0%) were Ag+/toxin+, 173 (67.1%) were Ag+/toxin-, and 18 (6.8%) were Ag-/toxin-. Mortality rates were as follows: Ag+/toxin+, 17.9% (12/67); Ag+/toxin-, 13.9% (24/173); Ag-/toxin-, 27.8% (5/18), P = 0.27. Among the EIA toxin negative patients who underwent chart review, 81% had 3 or more loose stools within 24 hours, 62% had abdominal pain, nausea, or vomiting, and 27% had a WBC &gt; 15.

Conclusion
The majority of patients testing positive for CDI by NAAT had a negative EIA test for toxin. There was no significant difference in mortality between EIA toxin positive and negative. Those with negative EIA toxin tests often had clinically significant symptoms of CDI. A two-stage CDI testing algorithm with NAAT followed by EIA for toxin may exclude patients with clinically significant CDI but would have resulted in a 75% reduction in reported NHSN LabID events.

Disclosures
All authors: No reported disclosures.
Clostridium difficile Laboratory Identification Event Reporting – A Need for Diagnostic Stewardship
Authors: Rock Clare , Pana Zoi , Leekha Surbhi , Trexler Polly , Andonian Jennifer , Gadala Avi , Carroll Karen C , Maragakis Lisa L 
Published: October 2017

Abstract

Background
Clostridium difficile LabID event reporting uses electronic laboratory results without chart review. Nucleic acid amplification testing is common in the US. A positive result may represent colonization or C. diff infection (CDI). We review C.difflabID events to ascertain if Hospital-Onest CDI (HO CDI). For non-HO CDI, we identify reason and use a matrix to prioritize clinical areas for intervention efforts.

Methods
Each C. difflab ID event from Jan 2015 to June 2016 at academic center had chart review for HO CDI; defined significant diarrhea, not present on admission, with no laxatives in prior 48 hours. For non HO-CDI events, reason and receipt of antibiotic treatment within 14 days of the positive test were retrospectively noted.
A prioritization matrix, where clinical services were ranked according to number of lab ID events (service’s contribution to the facility C. diffLabID), was multiplied by a rank based on percent of inappropriate tests giving an overall prioritization score for where intervention resources could potentially best be used.

Results
There were 490 C difficile LabID events; 284 (58%) were HO-CDI; 206 (42%) were inappropriate or delayed testing. Of the 190 with available medical records at time of retrospective review, reasons for not meeting the HO-CDI included laxative use within the previous 48 hours (41%), no clinically significant diarrhea (49.5%); delayed testing (9.5%). See figure. Of 172 patients with inappropriate testing, 159 (92%) were treated for CDI. Medicine and psychiatry ranked first and second on prioritization matrix. See table.

Conclusion
Nearly half of C. diff LabID events were not true HO CDI, but inappropriate or delayed tests. Prioritization matrix identified medicine and psychiatry as areas where diagnostic stewardship interventions could affect most on facility C. diff LabID.

Disclosures
K. C. Carroll, GenePOC, Inc.: Grant Investigator, Grant recipient
Association of Acid Suppression and Antimicrobial Use with Clostridium difficile Infection in Children
Authors: Huynh Hoang A , Wisdom Christy , Maples Holly D 
Published: October 2017

Abstract

Background
Clostridium difficileinfections (CDIs) can cause severe diarrhea and be potentially life-threatening, especially in children. Possible risk factors include age, being immunocompromised, prior antibiotic exposure, the use of antacids, and diseases that alter intestinal microbiota. Data in adults are vast while limited data is available in children. The objectives of this study are to identify pediatric risk factors and determine if an association between acid suppression and CDI’s in children exists.

Methods
A retrospective study was conducted between November 1, 2013 and October 31, 2016 at Arkansas Children’s Hospital. Children ages 1 – 18 years with a positive C. diff PCR test and ≥3 loose stools documented were included. Cases were excluded if previous positive PCR was within 60 days. Data collection included age, sex, encounter type (inpatient or outpatient), acid suppressing agents, previous antimicrobials within last 90 days and comorbidities including transplant, chronic pulmonary, hematology/oncology, and GI tract diseases. Statistical methods included descriptive analyses, χ2test, and Kruskal–Wallis test.

Results
A total of 139 cases of CDI among 123 patients were evaluated. Of these cases, the median (IQR) age is 8 years (3–13) with 77 (55.4%) being male and 86 (61.9%) of CDI cases identified inpatient of which 75 came from outpatient. Pediatric risk factors identified in C. diff cases included exposure to acid suppressing agents [61 (43.9%)] and antimicrobials [98 (70.5%)] with 90 (64.7%) having ≥1 comorbidities. Cases having ≥1 comorbidities were found to be associated with previous antacid exposure (P &lt; 0.0005) while antimicrobial(s) use was associated with CDI hospitalization (P = 0.001). Similarly, exposure to either antacid suppression or antimicrobials or both with comorbidities were found to have a significant association (P &lt; 0.0005) and associated with CDI hospitalization (P = 0.001).

Conclusion
Exposure to acid suppression in patients with comorbidities was associated with increased risk of CDI. Antimicrobial usage was associated with increased risk for hospitalization due to CDI. As pediatric outpatient antimicrobial stewardship evolves, improving CDI rates can center on improving antimicrobial and acid suppressive agents usage.

Disclosures
All authors: No reported disclosures.
A Randomized Trial of High-dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients
Authors: Natori Yoichiro , Humar Atul , Shiotsuka Mika , Slomovic Jaclyn , Hoschler Katja , Ferreira Victor , Ashton Peter , Rotstein Coleman , Lilly Les , Schiff Jeffrey , Singer Lianne , Kumar Deepali 
Published: October 2017

Abstract

Background
The annual influenza vaccine is recommended for solid-organ transplant recipients (SOTR) although studies have shown suboptimal immunogenicity. Influenza vaccine containing higher dose antigen may lead to greater immunogenicity in this population.

Method
We conducted a randomized, observer-blind trial comparing the safety and immunogenicity of high dose (HD; FluzoneHD, Sanofi) vs. standard dose (SD; Fluviral, GSK) influenza vaccine in adult SOTR. Patients were randomized 1:1 to receive the 2016–2017 influenza vaccine. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay for the three vaccine strains and an additional B strain not included in the vaccine.

Result
We randomized 172 patients and 161 (84 HD; 77 SD) were eligible for analysis. Median age was 57 years (range 18–86) and time from transplant was 38 (range 3–1402) months. Types of transplant were kidney 67 (39.0%), liver 38 (22.1%), lung 25 (14.5%), heart 23 (13.3%), and combined 19 (11.0%). Seroconversion to at least one of the three vaccine antigens (primary outcome) was present in 78.6% vs. 55.8% in HD vs. SD vaccine, respectively (P &lt; 0.001). Seroconversion to A/H1N1, A/H3N2, and B strains were 40.5% vs. 20.5%, 57.1% vs. 32.5%, and 58.3% vs. 41.6% in HD vs. SD vaccine (P = 0.006, 0.002, 0.028, respectively). Postimmunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group &#x2028;(P = 0.007, 0.002, 0.033). Independent factors associated with seroconversion to at least one vaccine strain were the use of HD vaccine and being on mycophenolate doses less than 2 g daily (P = 0.003, 0.013, respectively). Seroconversion rate to the B strain not included in the trivalent study vaccine was also higher in the HD vaccine group (33.3% vs. 14.1%, P = 0.004). Local and systemic adverse events were similar for the two vaccines. Biopsy-proven rejection was seen in 3.4% vs. 1.2% in HD vs. SD groups, respectively (P = 0.62). Two patients in the SD vaccine group and one in the HD group developed influenza infection during the follow-up.

Conclusion
High-dose vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population.

Disclosures
D. Kumar, Sanofi: Speaker’s Bureau, Speaker honorarium. Pfizer: Speaker’s Bureau, Speaker honorarium. GSK: Grant Investigator, Grant recipient.
The SEP-SEQ Trial: Clinical Validation of the Karius Plasma Next-Generation Sequencing Test for Pathogen Detection in Sepsis
Authors: Thair Simone , Seng Hon , Hollemon Desiree , Hong David , Blauwkamp Timothy , Kertesz Mickey , Ho Carine , Mann Rosen , Quinn James , Yang Samuel 
Published: October 2017

Abstract

Background
Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. In up to 40% of cases, a causative pathogen is never identified. There is a need for improved diagnostic tests that can accurately identify the breadth of potential pathogens to inform effective antimicrobial therapy.

Methods
We enrolled a prospective cohort of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were collected for NGS testing at time of initial blood culture. Extracted plasma cell-free DNA was sequenced, human sequences removed and remaining reads aligned against a pathogen database consisting of viruses, bacteria, and eukaryotic pathogens. Relative abundance was estimated; pathogens present at high statistical significance were identified. NGS results were compared with a composite reference standard of all microbiology testing performed within 7 days of admission and clinical diagnosis.

Results
Of 286 patients enrolled, plasma NGS identified potential pathogens in 60.1% (172 of 286) of septic subjects including DNA viruses, bacteria (including fastidious/unculturable bacteria like Mycobacterium tuberculosis), and fungi. In contrast, 15.7% (45 of 286) subjects had a positive initial blood culture and 38.1% (109 of 286) had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma assay had a positive agreement of 86.7% (39 of 45) and 79.5% (78 of 98) compared with initial blood culture (after excluding contaminants) and the composite laboratory reference standard, respectively. After clinical adjudication, 81.4% (140 of 172) of the positive plasma NGS results were deemed to be consistent with the septic event. Of the remaining 32 subjects, 15 had NGS results that were plausible causes of sepsis but clinical were insufficient to confirm this.

Conclusions
With a single blood draw, the Karius plasma NGS assay identified a broad range of pathogens in septic patients three times more often than blood culture and more often than all microbiology tests combined. This plasma NGS test can identify a viruses, bacteria, and eukaryotic pathogens which can provide valuable information to help clinicians better target antimicrobial therapy for patients with sepsis.

Disclosures
H. Seng, Karius, Inc.: Employee, Salary. D. Hollemon, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. T. Blauwkamp, Karius, Inc.: Employee, Salary. M. Kertesz, Karius, Inc.: Employee, Salary. S. Yang, Karius, Inc.: Research Contractor, Research grant.
Prevention of Recurrent Acute Uncomplicated Cystitis by Increasing Daily Water in Premenopausal Women: A Prospective, Randomized, Controlled Study
Authors: Hooton Thomas M , Vecchio Mariacristina , Iroz Alison , Tack Ivan , Dornic Quentin , Seksek Isabelle , Lotan Yair 
Published: October 2017

Abstract

Background
Increased hydration is commonly recommended as a preventive measure for women with recurrent acute uncomplicated cystitis (rAUC), but supportive data are sparse. The aim of this study was to assess the efficacy of increased daily water intake on the frequency of rAUC in premenopausal women.

Methods
140 healthy premenopausal asymptomatic women drinking less than 1.5 L of total fluid daily (24 hours) and suffering from rAUC (33 episodes in the past year) were randomized to receive, in addition to their usual daily fluid intake, either 1.5 L water daily (water group) or no additional fluids (control group), for 12 months. Assessments of daily water and total fluid intake, urine volume and osmolality, number of urine voids, and occurrence of AUC symptoms and a reminder to notify investigators of any such symptoms were performed at baseline, 6- and 12-month clinic visits in addition to monthly telephone calls. The primary outcome was frequency of rAUC episodes (31 AUC symptom and 3103 CFU/mL of a uropathogen in voided urine) over 12 months.

Results
Between baseline and 12 month’s follow-up, the water group, compared with the control group, had statistically significant increases in mean daily water intake (1.15 vs. −0.01 L), total fluid intake (1.65 vs. 0.03 L), urine volume (1.40 vs. 0.04 L), and number of urine voids (2.2 vs. −0.2), and a decrease in urine osmolality (−408 vs. −35 mOsm/Kg). The mean number of rAUC episodes in the water group was significantly less than in the control group (1.6 vs. 3.1; odds ratio 0.52, 95% CI 0.46–0.60, &#x2028;P &lt; 0.0001) (figure shows cumulative sum of AUC episodes over 12 months in both study groups). The mean number of antimicrobial regimens used to treat AUC events was 1.8 in the water group vs. 3.5 in the control group (P &lt; 0.0001). In addition, the mean number of days to first rAUC and the mean number of days between rAUC episodes was longer in the water group compared with the control group (148 vs. 93,&#x2028; P = 0.0005 and 143 vs. 85, P &lt; 0.0001, respectively).

Conclusions
Our results provide strong evidence that increased water intake is an effective antimicrobial-sparing preventive strategy for women with rAUC. Increasing daily water intake by approximately 1.5 L reduced rAUC episodes by 48% and antimicrobial regimens by 47% over 12 months.

Disclosures
M. Vecchio, Danone Research: Employee, Salary. A. Iroz, Dzanone Research: Employee, Salary. I. Tack, Danone Research: Consultant, Consulting fee and Speaker honorarium. Q. Dornic, Danone research: Employee, Salary. I. Seksek, Danone Research: Employee, Salary.
In-orbit performance of the soft X-ray imaging system aboard Hitomi (ASTRO-H)
Authors: Nakajima Hiroshi , Maeda Yoshitomo , Uchida Hiroyuki , Tanaka Takaaki , Tsunemi Hiroshi , Hayashida Kiyoshi , Tsuru Takeshi G , Dotani Tadayasu , Nagino Ryo , Inoue Shota , Ozaki Masanobu , Tomida Hiroshi , Natsukari Chikara , Ueda Shutaro , Mori Koji , Yamauchi Makoto , Hatsukade Isamu , Nishioka Yusuke , Sakata Miho , Beppu Tatsuhiko , Honda Daigo , Nobukawa Masayoshi , Hiraga Junko S , Kohmura Takayoshi , Murakami Hiroshi , Nobukawa Kumiko K , Bamba Aya , Doty John P , Iizuka Ryo , Sato Toshiki , Kurashima Sho , Nakaniwa Nozomi , Asai Ryota , Ishida Manadu , Mori Hideyuki , Soong Yang , Okajima Takashi , Serlemitsos Peter , Tawara Yuzuru , Mitsuishi Ikuyuki , Ishibashi Kazunori , Tamura Keisuke , Hayashi Takayuki , Furuzawa Akihiro , Sugita Satoshi , Miyazawa Takuya , Awaki Hisamitsu , Miller Eric D , Yamaguchi Hiroya 
Published: October 2017

Abstract
We describe the in-orbit performance of the soft X-ray imaging system consisting of the Soft X-ray Telescope and the Soft X-ray Imager aboard Hitomi. Verification and calibration of imaging and spectroscopic performance are carried out, making the best use of the limited data of less than three weeks. Basic performance, including a large field of view of ${38^{\prime }}$ × ${38^{\prime }}$, is verified with the first-light image of the Perseus cluster of galaxies. Amongst the small number of observed targets, the on-minus-off pulse image for the out-of-time events of the Crab pulsar enables us to measure the half-power diameter of the telescope as ∼${1 {^{\prime}_{.}} 3}$. The average energy resolution measured with the onboard calibration source events at 5.89 keV is 179 ± 3 eV in full width at half maximum. Light leak and crosstalk issues affected the effective exposure time and the effective area, respectively, because all the observations were performed before optimizing an observation schedule and the parameters for the dark-level calculation. Screening the data affected by these two issues, we measure the background level to be 5.6 × 10−6 counts s−1 arcmin−2 cm−2 in the energy band of 5–12 keV, which is seven times lower than that of the Suzaku XIS-BI.