bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative in vitro Activities of Ceftazidime–Avibactam and Ceftolozane-tazobactam Against Characterized β-Lactamase-producing Pseudomonas aeruginosa
Authors: Lin Lynn-Yao , Vail McClain , Debabov Dmitri , Critchley Ian 
Published: October 2017

Abstract

Background
Ceftazidime-avibactam (CAZ-AVI) and ceftolozane-tazobactam (TOL-TAZ) are cephalosporin/β-lactamase inhibitor combinations recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Both agents are reported to have antibacterial activity against P. aeruginosa including multi-drug-resistant strains, but few studies have directly compared the activities of both agents against the same strains in a single study. This study evaluated the activities of both agents against characterized β-lactamase-producing P. aeruginosa using broth microdilution (BMD) and disk diffusion (DD) methods.

Methods
A total of 98 clinical isolates of P. aeruginosa, including characterized β-lactamase-producing strains were tested for susceptibility to CAZ-AVI and TOL-TAZ using BMD and DD and results were interpreted using FDA/CLSI breakpoints. The isolates tested included CTX-M (ESBL), AmpC, KPC, OXA and metallo-β-lactamase (MBL) producing organisms. The results from both BMD and DD were analyzed to assess the correlation between the testing methods and ability to differentiate isolates susceptible and resistant to both agents.

Results
CAZ-AVI and TOL-TAZ exhibited similar MIC values against all isolates with MIC50/90 values of 2 and 16 µg/mL, respectively. When results were interpreted using FDA/CLSI breakpoints, the susceptibility rates for CAZ-AVI and TOL-TAZ were 82.7% and 62.2%, respectively. Isolates resistant to CAZ-AVI were predominantly MBL-producers whereas isolates resistant to TOL-TAZ included both MBL and KPC-producing P. aeruginosa. Both agents were active against AmpC-producing P. aeruginosa and both agents showed good correlation between BMD and DD methods.

Conclusion
CAZ-AVI and TOL-TAZ were active against β-lactamase-producing subsets of P. aeruginosa isolates in this challenge set. Both AmpC and KPC-producing P. aeruginosa were susceptible to CAZ-AVI whereas TOL-TAZ activity was limited to AmpC-producing organisms. Neither agent was active against MBL-producing organisms.

Disclosures
L. Y. Lin, Allergan plc: Employee, Salary; M. Vail, Allergan plc: Employee and Intern during study conduct and analysis, Educational support; D. Debabov, Allergan plc: Employee, Salary; I. Critchley, Allergan plc: Employee, Salary
CD4+ T Cells Specific for C. difficile Toxins are a Marker of Patients with Active Relapsing Disease
Authors: Cook Laura , Wong May , Rees William , Lau Torey , Levings Megan , Steiner Theodore 
Published: October 2017

Abstract

Background
The bacterial pathogen Clostridium difficile is the leading cause of nosocomial infectious diarrhea. Although C. difficile infection (CDI) can be treated with antibiotics, approximately 25% of patients relapse after treatment. The pathogenicity of CDI requires the activities of its toxins, TcdA and TcdB, but T cell-mediated responses to these toxins remain uncharacterized.

Methods
We enrolled two cohorts of patients, one with newly acquired CDI (n = 14) and the other with relapsing CDI (n = 25); and healthy volunteers with no history of CDI (n = 12). We measured peripheral blood CD4+ T cell responses to the toxins using a whole blood flow cytometry assay that identifies antigen-specific CD4+ T cells by co-expression of CD25 and OX40 following 44h incubation with antigen (Fig 1).

Results
We found that in patients with recurring CDI, T cell responses to TcdB were significantly higher than in healthy controls (median 1.04% vs. 0.18%; P = 0.003, Fig 2). In contrast, TcdA T cell responses and anti-TcdA/TcdB IgG titres were not different between recurring patients and controls. TcdB, but not TcdA, T cell responses were significantly higher in recurring CDI compared with newly acquired CDI (median 1.04% vs. 0.44%; P = 0.032). In both patient cohorts TcdB-specific CD4+ T cells were functionally heterogeneous, on average: 25% expressed the gut homing marker integrin β7; there was a 1:1 ratio of Tregs to T effectors; and T effectors contained Th1, Th2 and Th17 cells at a 1.5:1:3 ratio. The proportion of Th1 and Th17 cells within TcdB-specific CD4+ T cells was also significantly reduced in recurring, compared with newly acquired, CDI (Fig 3). Analysis of sorted TcdB-specific CD25+OX40+ cells confirmed specificity for TcdB and polarization towards Th17 cells, which are important for intestinal anti-pathogen immunity.

Conclusion
This is the first investigation of T cell immunity to C. difficile toxins. Our data show that anti-TcdB CD4+ T cell responses are a more specific marker of disease than IgG titres. Tracking how toxin-specific CD4+ T cell responses change following treatment and/or vaccination not only has the potential to predict relapse, but also to deliver insight into how CD4+ T cell memory develops in response to this prevalent pathogen.

Disclosures
All authors: No reported disclosures.
Comparison of Fidaxomicin and Vancomycin for Recurrent Clostridium difficile Colitis
Authors: Khoo Teresa , Fleischner Zachary , Chow Robert , Monteforte Melinda , Marcos Luis A 
Published: October 2017

Abstract

Background
Fidaxomicin is a narrow spectrum macrocyclic antibiotic used for the treatment of Clostridium difficileinfection (CDI). The objective of this study is to compare the recurrence and mortality rates of patients with CDI who received either vancomycin or fidaxomicin at Stony Brook University Hospital.

Methods
A retrospective chart review was performed to identify all hospitalized patients who received fidaxomicin and vancomycin for CDI for the period 2011–2015. Inclusion criteria included patient age ≥18 years, stool positive PCR test for C. difficile and being treated ≥10 days of either fidaxomicin or vancomycin orally. Clinical recurrence was defined as a return of diarrhea, a positive test for C. difficiletoxin B and a need for retreatment for CDI within 90 days of cessation of therapy.

Results
A total of 55 (52.7% male) and 74 (51.4% male) cases met inclusion criteria in the fidaxomicin (F) and vancomycin (V) groups, respectively. The mean age was 65.9 ± 1.88 and 63.7 ± 1.86 years in group F and V respectively (P = 0.4). Median length of hospitalization was 14 and 9 days for F and V respectively (P = 0.6). Both groups had similar proportions on the following variables: immunosuppression (V 36.5% vs. F 36.4%; P = 0.9), ≥ 1 prior episode of CDI (V 59.5% vs. F 61.8%; P = 0.8), sepsis on admission (V 29.7%, F 36.4%; P = 0.4), the use of any antibiotic during the last 30 days (V 74.3%, 71%, P = 0.7), and treatment with additional anti-CDI therapy (V 24.3%, F 29.1%; P = 0.5). CDI recurrence rate was 24% (V) and 40% (F, P = 0.057). The 90-day mortality rate was 4.1% in the vancomycin group and 10.9% in the fidaxomicin group (P = 0.13).

Conclusion
Fidaxomicin had a higher recurrent CDI than vancomycin in this tertiary medical center.

Disclosures
All authors: No reported disclosures.
Charismatic Signaling
Authors: Shaver John , Fraser Gloria , Bulbulia Joseph 
Published: October 2017

Abstract
This chapter describes an evolutionary model of religion called “charismatic signaling.” The theory focuses on features of religion that express automated within-group cooperation—that is, cooperation that does not rely on strategic reasoning or explicit social prediction. The model is interesting because it explains otherwise puzzling features of religious systems. Such puzzles range from intrinsic religious motivations to ritual human sacrifice as evolved adaptations for social coordination. An additional virtue of the model is that it explains the reliability of cooperation with strangers who cannot observe or assess cooperative intentions directly or by reputation. The chapter describes the intellectual motivations for charismatic signaling theory and outlines ethnographic and historical puzzles the theory solves.
A Review of CBT Treatments for Substance Use Disorders
Authors: Morin Jean-François G. , Harris Maggie , Conrod Patricia J. 
Published: October 2017

Abstract
This review article presents a summary of the existing literature on well-established CBT treatments for substance use disorder. It provides an overview of the origins, procedure, and evidence for six CBT treatment models: relapse prevention (RP) and mindful-based relapse prevention (MBRP), guided self-change (GSC), community reinforcement approach (CRA), behavioral couples therapy (BCT), and personality-targeted brief interventions. Common intervention components include orienting clients towards a meaningful goal, teaching necessary skills to reduce substance use and successfully achieve the goal, and establishing plans to face potential relapses, which generally appear to produce moderate to large effects across contexts and substance-related outcomes.
Modelling of deep gaps created by giant planets in protoplanetary disks
Authors: Kanagawa Kazuhiro D. , Tanaka Hidekazu , Muto Takayuki , Tanigawa Takayuki 
Published: October 2017

Abstract
A giant planet embedded in a protoplanetary disk creates a gap. This process is important for both theory and observation. Using results of a survey for a wide parameter range with two-dimensional hydrodynamic simulations, we constructed an empirical formula for the gap structure (i.e., the radial surface density distribution), which can reproduce the gap width and depth obtained by two-dimensional simulations. This formula enables us to judge whether an observed gap is likely to be caused by an embedded planet or not. The propagation of waves launched by the planet is closely connected to the gap structure. It makes the gap wider and shallower as compared with the case where an instantaneous wave damping is assumed. The hydrodynamic simulations show that the waves do not decay immediately at the launching point of waves, even when the planet is as massive as Jupiter. Based on the results of hydrodynamic simulations, we also obtained an empirical model of wave propagation and damping in cases of deep gaps. The one-dimensional gap model with our wave propagation model is able to reproduce the gap structures in hydrodynamic simulations well. In the case of a Jupiter-mass planet, we also found that the waves with a smaller wavenumber (e.g., m = 2) are excited and transport the angular momentum to a location far away from the planet. The wave with m = 2 is closely related with a secondary wave launched by a site opposite from the planet.
Terrible Twos or Early Signs of Psychopathology? Developmental Patterns in Early Identified Preschoolers With Cochlear Implants Compared With Hearing Controls
Authors: Netten Anouk P. , Rieffe Carolien , Ketelaar Lizet , Soede Wim , Gadow Kenneth D. , Frijns Johan H. M. 
Published: October 2017

Objective:
Cochlear implants (CIs) have dramatically improved the lives of children who are deaf or hard of hearing; however, little is known about its implications for preventing the development of psychiatric symptoms in this at-risk population. This is the first longitudinal study to examine the early manifestation of emotional and behavioral disorders and associated risk and protective factors in early identified preschoolers with CIs compared with hearing peers.

Design:
Participants were 74 children with CIs and 190 hearing controls between ages 1 and 5 years (mean age, 3.8 years). Hearing loss was detected using the Newborn Hearing Screening in The Netherlands and Flanders. Parents completed the Early Childhood Inventory-4, a well-validated measure, to evaluate the symptoms of DSM-IV–defined psychiatric disorders, during three consecutive years. Language scores were derived from each child’s medical notes.

Results:
Children with CIs and hearing controls evidenced comparable levels of disruptive behavior and anxiety/depression (which increased with age in both groups). Greater proficiency in language skills was associated with lower levels of psychopathology. Early CI and longer duration of CI use resulted in better language development. In turn, higher early language skills served as a protective factor against the development of disruptive behavior symptoms.

Conclusions:
This longitudinal study uniquely shows that improvement in language skills mitigates the development of early signs of psychopathology. Early identification of hearing loss and CIs help children improve their language skills.
Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Authors: Mehta Akash , Mittal Rohin , Chandrakumaran Kandiah , Carr Norman , Dayal Sanjeev , Mohamed Faheez , Moran Brendan , Cecil Tom 
Published: October 2017

BACKGROUND:
Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE:
The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients.

DESIGN:
Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records.

SETTINGS:
The study was conducted at a high-volume tertiary referral center for peritoneal malignancy.

PATIENTS:
Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included

MAIN OUTCOME MEASURES:
A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy.

RESULTS:
Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1–28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8–127.0 mo) and 102.1 months (95% CI, 84.3–119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%.

LIMITATIONS:
The retrospective nature limits the interpretation of these results.

CONCLUSIONS:
Complete cytoreduction was achieved in all of the patients, with excellent long-term survival. The incidence of peritoneal spread (57%) compared with nodal involvement (15%) supports cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as definitive treatment rather than prophylaxis in patients with high-grade appendix tumors, even without radiologically detectable disease. High-grade appendix tumors benefit from early aggressive operative management to deal with potential peritoneal and nodal spread and should be considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. See Video Abstract at http://links.lww.com/DCR/A360.
Association Among Obesity, Metabolic Health, and the Risk for Colorectal Cancer in the General Population in Korea Using the National Health Insurance Service–National Sample Cohort
Authors: Shin Cheol Min , Han Kyungdo , Lee Dong Ho , Choi Yoon Jin , Kim Nayoung , Park Young Soo , Yoon Hyuk 
Published: October 2017

BACKGROUND:
In Korea, the incidence of colorectal cancer has increased and obesity is on a rising trend because of a Westernized lifestyle in men.

OBJECTIVE:
The purpose of this study was to evaluate the relationship between metabolic health status, as well as BMI, and the incidence of colorectal cancer.

DESIGN:
This was a prospective cohort study.

SETTINGS:
The study was conducted with the National Health Insurance Service–National Sample Cohort.

PATIENTS:
A total of 408,931 Korean adults without cancer at baseline were followed up until 2013 (mean follow-up, 9 y).

MAIN OUTCOME MEASURES:
Demographic, anthropometric, and laboratory data at baseline were collected and categorized. The presence of diabetes mellitus, hypertension, and dyslipidemia was defined using the criteria of previous studies. The incidence of colorectal cancer was also defined according to the International Classification of Disease, 10th Revision, codes and the claim data on endoscopy with biopsy.

RESULTS:
During the follow-up, 5108 new cases of colorectal cancer occurred. Being underweight (<18.5 kg/m2) reduced the risk for colorectal cancer among women (adjusted HR = 0.646 (95% CI, 0.484–0.863)), whereas high BMI significantly increased the risk in men and in the elderly. Obesity (≥25 kg/m2), diabetes mellitus, and hypertension were identified as risk factors for colorectal cancer in men but not for women. Although metabolically unhealthy nonobese men had a higher risk for colorectal cancer than metabolically healthy nonobese men (adjusted HR = 1.114 (95% CI, 1.004–1.236)), the risk was lower than that in the obese men.

LIMITATIONS:
The study population consisted of people who underwent health examinations, thus there could be selection bias.

CONCLUSIONS:
In Korean adults, obesity contributes to the incidence of colorectal cancer with a sex difference. Nonobese but metabolically unhealthy men are considered to be a high-risk group for colorectal cancer, but obesity itself is more important in colorectal carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A475.
Bowel Dysfunction Related to Spina Bifida: Keep It Simple
Authors: Brochard Charlène , Peyronnet Benoît , Dariel Anne , Ménard Hélène , Manunta Andréa , Ropert Alain , Neunlist Michel , Bouguen Guillaume , Siproudhis Laurent 
Published: October 2017

BACKGROUND:
Although care of urological disorders in spina bifida is well established, there is yet no agreement on a standardized approach to bowel dysfunction in this population.

OBJECTIVE:
The purpose of this study was to assess bowel dysfunction using validated instruments and the risk factors in adults with spina bifida.

DESIGN:
A multidisciplinary team prospectively collected patient data, focusing on anorectal and urological symptoms.

SETTINGS:
The study was conducted with data from a French referral center for spina bifida.

PATIENTS:
A total of 228 adults with spina bifida (sex ratio men:women, 92 (40%):136 (60%)) with a median age of 34.7 years (range, 26.8–44.7 y) were assessed.

MAIN OUTCOMES MEASURES:
Factors associated with severe fecal incontinence (Cleveland Clinic Incontinence Score ≥9) and severe bowel dysfunction (Neurogenic Bowel Dysfunction score ≥14) were assessed in a multivariate analysis model.

RESULTS:
The prevalence rates of severe fecal incontinence and severe bowel dysfunction were 60% (130/217) and 42% (71/168). Bowel dysfunction was the second most common major concern of patients after lower urinary tract dysfunction. Male sex, obesity, urinary incontinence, and a Knowles–Eccersley–Scott symptom constipation score ≥10 were independently associated with severe fecal incontinence. Patients with soft stools had significantly less severe bowel dysfunction. Neither neurologic level nor other neurologic features of spina bifida were associated with severe fecal incontinence or severe bowel dysfunction.

LIMITATIONS:
The recruitment of patients with spina bifida through a national referral center might have resulted in selection bias, and some data were missing especially regarding BMI and Neurogenic Bowel Dysfunction score (21% and 26% of missing data).

CONCLUSIONS:
The prevalence rates of severe fecal incontinence and severe bowel dysfunction in adults with spina bifida were high and were adequately perceived by the patients. The present study emphasized the association of bowel dysfunction and fecal incontinence with obesity, urologic disorders, and stool consistency rather than neurologic features. See Video Abstract at http://links.lww.com/DCR/A394.
Acute Kidney Injury Due to Systemic Absorption of Antibiotics Impregnated in a Bone Cement Spacer
Authors: Nakasone Trisha S. , Multani Ashrit , Chary Aarthi , Renault Cybele A. , Winslow Dean L. 
Published: October 2017

Abstract
We report a case of acute kidney injury due to systemic absorption of tobramycin, gentamicin, and vancomycin from an antibiotic-impregnated cement spacer placed during revision of an infected total knee arthroplasty. The continual systemic antibiotic absorption and resultant nephrotoxicity required spacer removal, with subsequent improvement in renal function.
Evaluation of Intervention Fidelity in a Multisite Clinical Trial in Persons With Multiple Sclerosis
Authors: Morrison Janet D. , Becker Heather , Stuifbergen Alexa K. 
Published: October 2017

ABSTRACT

Background: Careful consideration of intervention fidelity is critical to establishing the validity and reliability of research findings, yet such reports are often lacking in the research literature. It is imperative that intervention fidelity be methodically evaluated and reported to promote the translation of effective interventions into sound evidence-based practice. Purpose: The purpose of this article is to explore strategies used to promote intervention fidelity, incorporating examples from a multisite clinical trial, that illustrate the National Institutes of Health Behavior Change Consortium’s 5 domains for recommended treatment practices: (1) study design, (2) facilitator training, (3) intervention delivery, (4) intervention receipt, and (5) intervention enactment. A multisite randomized clinical trial testing the efficacy of a computer-assisted cognitive rehabilitation intervention for adults with multiple sclerosis is used to illustrate strategies promoting intervention fidelity. Methods: Data derived from audiotapes of intervention classes, audits of computer exercises completed by participants, participant class attendance, and goal attainment scaling suggested relatively high fidelity to the intervention protocol. Conclusion: This study illustrates how to report intervention fidelity in the literature guided by best practice strategies, which may serve to promote fidelity monitoring and reporting in future studies.