bluuebunny/crossref_metadata_2025_split huggingface dataset:
P040 DEPRESSION SCREENING IN A PEDIATRIC IBD CENTER
Authors: Talmadge Clair , Lewis Glen , Gold Benjamin , Gomez Samantha , Reed Bonney , Dykes Dana 
Published: January 2020

Abstract

Introduction
Depression is a common pediatric problem affecting approximately 25% of U.S. adolescents and up to 35% of patients with Inflammatory Bowel Disease (IBD). Suicide is associated with mood disorders and is a leading cause of death for youth ages 10–25. Despite known risks of depression, up to 75% of depressed youth go unrecognized. Recently published guidelines recommend annual screening for youth 12 and older diagnosed with IBD (Mackner et al., 2019). We sought to implement these guidelines in a large outpatient pediatric gastroenterology practice.

Methods
We used quality improvement (QI) methodology and Plan-Do-Study-Act (PDSA) cycles to design and implement a pilot screening process for depression. We aimed to prospectively screen at least 80% of patients diagnosed with IBD who were at least 13 years old from March 3, 2019 to October 11, 2019. Screening was done using the PHQ-9, a brief and validated screening tool widely used in the medical setting. Initial steps of the PDSA cycle focused on training in tool administration, as well as scoring of the PHQ-9 simulated interviews, management of suicidal ideation, and office staff training. Next steps included eligible patient identification and distribution of screeners. As screening processes were improved, we focused on streamlining process of screener distribution and scoring during the visit, as well as disposition of patients based on screening results. The ImproveCareNow Depression Screening Toolkit was used as a resource for implementation.

Results
During the study period, screening of all eligible patients with IBD was implemented across three pediatric gastroenterologists within the larger practice of 15 physicians. Weekly screenings improved from 0% per week to over 80% per week at the culmination of this 32-week pilot. Across the pilot, a total of 141 patients were screened, and of these, 32% had actionable scores indicating mild, moderate, or severe depressive symptoms, with 7 of these endorsing suicidal thoughts.

Conclusions
Development and implementation of a depression screening protocol in an IBD outpatient clinic is feasible and sustainable. A large number of patients were affected by depression and many were previously unrecognized. Next steps include expansion to a larger number of providers and automation of screening tools.
P044 HIGH STRESS REACTIVITY AND SYMPTOM FLARES IN ULCERATIVE COLITIS PATIENTS
Authors: Sauk Jenny , Ryu Hyo Jin , Labus Jennifer , Liu Cathy , Stains Jean , Dvorsky Miriam , Lagishetty Venu , Naliboff Bruce , Jacobs Jonathan , Mayer Emeran 
Published: January 2020

Abstract
Psychological stress has long been implicated as a cause of symptom relapse in IBD. Whether psychological stress is associated with alterations in the brain-gut-microbiome (BGM) axis and intestinal inflammation requires further investigation.
Aims: We hypothesize that stress-induced changes in BGM interactions play a role in the development of symptomatic flares in patients with ulcerative colitis (UC). We aimed to test this hypothesis in a prospective study of 100 UC patients in clinical remission to identify gut microbiome, brain network connectivity, and stress-associated biomarkers of UC patients at baseline that can predict the risk of future symptomatic flares.
Methods: Ninety-four subjects in clinical remission (Mayo score ≤ 1 AND Simple Colitis Clinical Activity Index (SCCAI) score &lt; 5) underwent comprehensive phenotyping, including clinical and behavioral assessments, brain imaging, and autonomic testing for heart rate variability (HRV) and electrodermal activity (EDA) before, during, and after a 3 minute arithmetic stress test at baseline, with longitudinal follow-up every 3 months and at time of flare. Clinical flares (SCCAI &gt;5) and subjective flares (“Do you think you are in a flare?”) were assessed. Fecal calprotectin has been collected at baseline and every 3 months and at time of flare.
Results: To date, there have been 18 clinical flares (19%) and 8 symptomatic flares (8.5%) in 94 patients over a mean follow-up time of 8.1 months. Baseline measurements have identified two clusters of patients (low stress reactivity in cluster 1, high stress reactivity in cluster 2), based on trait anxiety (International Personality Item Pool [IPIP]-Neuroticism), and perceived stress (Cohen’s Perceived Stress Scale) measured at baseline. These groups differed in the frequency of clinical flares (9.3% vs. 27.4%, p=0.03) and subjective flares (3.6% vs. 11.8%, p=0.28), respectively. There were no cluster differences in heart rate variability, but there was overall greater EDA noted in the high stress reactivity group (EDA: 3.99 (SE: 0.27) vs. 5.02 (SE: 0.25); p=0.007).
Conclusions: Based on our current results, the frequency of symptomatic flares in UC patients in clinical remission is predicted by measures of perceived stress and trait anxiety and by heightened sympathetic arousal as measured by electrodermal activity. We expect that gut microbiome profiles and brain imaging networks will further delineate the stress-responsive subset of UC patients with heightened flare risk and that fecal calprotectin levels collected will confirm whether the stress-responsive subset of UC patients experiences biochemical flare with increase in symptoms.
P093 IDENTIFICATION OF PATIENTS AT RISK OF SUBTHERAPEUTIC DRUG EXPOSURE PRIOR TO INITIATION OF CERTOLIZUMAB PEGOL THERAPY FOR THE TREATMENT OF CROHN’S DISEASE
Authors: Lefevre Pavine , Guizzetti Leonardo , Feagan Brian , Pop Anca , Yassine Mohamed , Sandborn William , Casteele Niels Vande 
Published: January 2020

Abstract

Background
Certolizumab pegol (CZP) is effective treatment for moderately-to-severely active Crohn’s disease (CD)1, 2 at approved subcutaneous doses of 400 mg on weeks 0, 2 and 4 (induction) and every 4 weeks thereafter (maintenance). Prior research has demonstrated a relationship between CZP drug exposure and outcomes, with higher plasma CZP concentrations during induction and maintenance therapy associated with more favorable clinical, endoscopic and biologic (C-reactive protein [CRP], fecal calprotectin [FC]) disease outcomes.3 Increased drug clearance is the driver of subtherapeutic CZP concentrations, although the identification of patients at risk for accelerated clearance prior to therapy initiation has not previously been possible.

Methods
A population pharmacokinetic model4 was used to estimate baseline CZP clearance (i.e., at the time of therapy initiation) using baseline clinical variables (i.e., gender, body weight, albumin and CRP concentration) available from patients with CD previously included in nine randomized, controlled, phase 2 and 3 trials (N=2157). Baseline CZP clearance was compared between patients who achieved observed Week 6 CZP plasma concentrations previously associated with meaningful clinical (&gt;36 μg/mL for Crohn’s Disease Activity Index [CDAI] ≤ 150), biologic (&gt;44 μg/mL for FC ≤ 250 μg/g) and composite clinical and biologic (&gt;48 μg/mL for CDAI ≤ 150 and FC ≤ 250 μg/g) outcomes at Week 6. Receiver operating characteristic curve analysis identified baseline CZP clearance thresholds associated with effective CZP concentrations at Week 6.

Results
Baseline CZP clearance was significantly higher in patients not achieving effective Week 6 CZP plasma concentration thresholds of 36 μg/mL, 44 μg/mL and 48 μg/mL compared to patients who achieved these thresholds (Figure 1; p&lt;0.0001 for all comparisons). Baseline CZP CL of ≥ 0.5 L/day was associated with subtherapeutic observed Week 6 CZP plasma concentrations. The sensitivity, specificity, likelihood ratios and area under the concentration curves for the association between baseline CZP clearance and observed Week 6 CZP concentration thresholds are shown in Table 1.

Conclusion
Patients with CD who have accelerated baseline CZP clearance are at risk of subtherapeutic CZP concentrations. Clearance can be calculated using baseline clinical variables and would allow for identification of patients for whom therapeutic CZP concentrations may be achieved with current approved dosing. Implementing therapeutic drug monitoring may increase the likelihood of achieving therapeutic drug exposure during induction as well as treatment success.

References
P088 REAL-WORLD EXPERIENCE WITH TOFACITINIB FOR THE MANAGEMENT OF CROHN’S COLITIS
Authors: Kumar Anand , Gordon Benjamin , Yang Stevie , Longman Randy , Scherl Ellen , Battat Robert , Lukin Dana 
Published: January 2020

Abstract

Background
Treatment options in Crohn’s disease (CD) are limited. Tofacitinib, a Janus Kinase 1–3 inhibitor, is not currently approved for use in CD, however, its effect on biochemical markers suggests that tofacitinib does impact disease activity in CD.

Aim
To evaluate the real-world experience with off-label tofacitinib in the treatment of Crohn’s colitis at a large inflammatory bowel disease center.

Methods
We evaluated 5 adult patients with moderate-to-severely active Crohn’s colitis who were started on tofacitinib therapy after failing ≥2 biologic agents. Pre- and post-tofacitinib treatment characteristics including clinical, endoscopic and biochemical disease activity, presence of extra-intestinal manifestations, and potential adverse effects were recorded (figure 1). Endpoints evaluated were clinical remission [defined as Harvey Bradshaw index (HBI) &lt;4) and response (&gt;50% reduction in HBI); endoscopic remission (simple endoscopic score (SES)-CD&lt;3) and response (&gt;50% reduction in SES-CD); and biochemical remission [fecal calprotectin (FC)&lt;50 μg/g)].

Results
Post-tofacitinib, patients were followed for a median period of 18 weeks (range 8–34 weeks). Four of the 5 (80%) patients achieved clinical remission, 4/5 (80%) achieved clinical response. All patients that underwent a follow-up endoscopy (n=3) achieved endoscopic response and 2/3 (67%) achieved endoscopic remission (figure 2). Three of the 4 patients with a follow-up FC (75%) achieved biochemical remission. Of the 4 patients on baseline corticosteroids, 3 (75%) were corticosteroid-free by week 18. Four of the 5 (80%) patients exhibited improvement in CD-related arthropathy. No significant treatment-emergent adverse events were observed.

Conclusions
In this case series, use of tofacitinib was safe and effective in the treatment of refractory Crohn’s colitis and CD-related arthropathy. Further investigation of tofacitinib in CD, particularly involving the colon, is warranted.
Correlation without a cause: an epidemiological odyssey
Authors: Davey Smith George , Phillips Andrew N 
Published: January 2020

Background
In the 1980s debate intensified over whether there was a protective effect of high-density lipoprotein cholesterol (HDL-C) or an adverse effect of triglycerides on coronary heart disease (CHD) risk. In a 1991 paper reprinted in the IJE we suggested that the high degree of correlation between the two, together with plausible levels of measurement error, made it unlikely that conventional epidemiological approaches could contribute to causal understanding. The consensus that HDL-C was protective, popularly reified in the notion of ‘good cholesterol’, strengthened over subsequent years. Reviewing the biostatistical and epidemiological literature from before and after 1991 we suggest that within the observational epidemiology pantheon only Mendelian randomization studies—that began to appear at the same time as the initial negative randomized controlled trials—made a meaningful contribution. It is sobering to realize that many issues that appear suitable targets for epidemiological investigation are simply refractory to conventional approaches. The discipline should surely revisit this and other high-profile cases of consequential epidemiological failure—such as that with respect to vitamin E supplementation and CHD risk—rather than pass them over in silence.
OccIDEAS: web-based assessment of occupational agent exposure
Authors: Fritschi Lin , Sadkowsky Troy , Glass Deborah C 
Published: January 2020

AbstractMost epidemiological studies of disease aetiology do not consider potential risk factors at work. This may be because work is a complex exposure: people usually have a series of different jobs over their working lifetime; within each job there may be a range of different tasks; and there may be a variety of exposures in each job. Because of this complexity, many epidemiologists do not have the expertise or training to assess occupational exposures accurately. Our web-based application, OccIDEAS, manages the process of occupational agent assessment in epidemiological studies. The epidemiologist chooses the agents of interest for the study and OccIDEAS provides an online set of questionnaires that are tailored to those agents. The participant is asked specific questions about their job and evidence-based algorithms provide an assessment of exposure to each agent. OccIDEAS puts the world’s best occupational epidemiological expertise within reach of any researcher.
Energy-preserving methods for nonlinear Schrödinger equations
Authors: Besse Christophe , Descombes Stéphane , Dujardin Guillaume , Lacroix-Violet Ingrid 
Published: January 2020

Abstract
This paper is concerned with the numerical integration in time of nonlinear Schrödinger equations using different methods preserving the energy or a discrete analogue of it. The Crank–Nicolson method is a well-known method of order $2$ but is fully implicit and one may prefer a linearly implicit method like the relaxation method introduced in Besse (1998, Analyse numérique des systèmes de Davey-Stewartson. Ph.D. Thesis, Université Bordeaux) for the cubic nonlinear Schrödinger equation. This method is also an energy-preserving method and numerical simulations have shown that its order is $2$. In this paper we give a rigorous proof of the order of this relaxation method and propose a generalized version that allows one to deal with general power law nonlinearites. Numerical simulations for different physical models show the efficiency of these methods.
Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2)
Authors: Maggiolo F , Gianotti N , Comi L , Di Filippo E , Fumagalli L , Nozza S , Galli L , Valenti D , Rizzi M , Castagna A 
Published: January 2020

Abstract

Background
We explored the combination of rilpivirine plus cobicistat-boosted darunavir [a two-drug regimen (2DR)] when switching from standard triple combined ART.

Methods
In this randomized, open-label, non-inferiority trial, participants had an HIV-RNA &lt;50 copies/mL on a stable (&gt;6 months) three-drug regimen. The primary endpoint was proportion with HIV-RNA &lt;50 copies/mL at Week 24 (snapshot algorithm), with a –12% non-inferiority margin. ClinicalTrials.gov: NCT04064632.

Results
One hundred and sixty patients were allocated (1:1) to 2DR or to continue current ART (CAR). At Week 24, 72 (90.0%) of participants with 2DR and 75 (93.8%) with CAR maintained HIV-RNA &lt;50 copies/mL [difference −3.75% (95% CI = −11.63 to 5.63)], confirming non-inferiority. Non-inferiority was confirmed considering an HIV-RNA &gt;50 copies/mL (0% for 2DR; 3.7% for CAR; 95% CI = −0.4 to 7.9). Four patients reported adverse events not leading to treatment discontinuation (one patient in the 2DR group and three patients in the CAR group); eight subjects discontinued therapy in the 2DR group and three in the CAR group. With 2DR, lipid serum concentrations increased, but differences were statistically significant only for tenofovir disoproxil fumarate-containing CAR and in 2DR patients receiving a pre-switch regimen including tenofovir disoproxil fumarate. Median bone stiffness decreased in the CAR group from 86.1 g/cm2 (IQR = 74–98) to 83.2 g/cm2 (IQR = 74–97) and increased in the 2DR group from 84.9 g/cm2 (IQR = 74–103) to 85.5 g/cm2 (IQR = 74–101). The reduction within the CAR group was significant (P = 0.043).

Conclusions
Once-daily rilpivirine plus cobicistat-boosted darunavir is an effective 2DR that combines a high virological efficacy with a potential to avoid major NRTI toxicities.
Evaluation of effectiveness and compliance with the mupirocin nasal ointment part of Staphylococcus aureus decolonization in real life using UPLC-MS/MS mupirocin quantification
Authors: Nicolas Roxane , Carricajo Anne , Morel Jérôme , Rigaill Josselin , Grattard Florence , Guezzou Salim , Audoux Estelle , Campisi Salvatore , Favre Jean-Pierre , Berthelot Philippe , Verhoeven Paul O , Botelho-Nevers Elisabeth 
Published: January 2020

Abstract

Background
Preoperative decolonization is recommended in Staphylococcus aureus nasal carriers scheduled for cardiac surgery. We aimed to evaluate the effectiveness of and compliance with mupirocin use in nasal S. aureus carriers in a real-life setting.

Methods
Prospective study including consecutive patients scheduled for cardiac surgery screened for S. aureus nasal carriage at preoperative consultation. Carriers were prescribed mupirocin nasal ointment, chlorhexidine shower and mouthwash. Effectiveness of decolonization was evaluated with a postoperative nasal sample. Compliance was evaluated objectively by determination of nasal mupirocin concentration using UPLC-MS/MS and self-reported by questionnaire.

Results
Over 10 months, 361 patients were included, 286 had preoperative screening, 75 (26.2%) were S. aureus nasal carriers and 19 of them (25.3%) failed to be effectively decolonized. No resistance to mupirocin was documented. Preoperative and postoperative strains were identical in all cases. Declared good compliance was associated with decolonization success (OR = 24; 95% CI 4–143, P &lt; 0.0001). Mupirocin detection was significantly associated with the level of compliance. Mupirocin was detected in 52.2% (24/46) of patients effectively decolonized and in 12.5% (2/16) of patients with decolonization failure (P &lt; 0.01). In 2/19 patients, failure of decolonization was not associated with a compliance issue. Postoperative carriage was associated with an increased risk of S. aureus infection (OR = 9.8; 95% CI 1.8–53, P &lt; 0.01).

Conclusions
In real life, decolonization is not always effective, hence there is a persisting risk of S. aureus endogenous infection. Mupirocin concentration measurement may help to understand compliance issues and failures in decolonization.
Raising awareness of antimicrobial resistance among the general public in the UK: the role of public engagement activities
Authors: Redfern James , Bowater Laura , Coulthwaite Lisa , Verran Joanna 
Published: January 2020

Abstract
In response to the accepted risk of emerging antimicrobial resistance, many organizations and institutions have developed and delivered events and activities designed to raise awareness of the issue and to change the behaviour of the intended audience. However, few of these events for a general public audience are documented or able to be sourced by those who might wish to repeat, adapt or modify, particularly those events that are successful. ‘Insider knowledge’ appears to be the best search tool. Moreover, evaluation of the success or impact of the event is rarely published. It would be useful if there were a ‘hub’ where descriptions of such activities could be deposited, enabling the building of a significant resource with real academic value.
A Rapid Method for the Detection of Diarrhetic Shellfish Toxins and Azaspiracid Shellfish Toxins in Washington State Shellfish by Liquid Chromatography Tandem Mass Spectrometry
Authors: Yang Li , Singh Avi , Lankford Shelley K , Stuart James , Rice Daniel , Wu Wen-Hsin , Hungerford James M 
Published: January 2020

AbstractBackgroundDiarrhetic shellfish toxins (DSTs) in domestic shellfish and azaspiracids (AZAs) in imported products are emerging seafood safety issues in the United States. In addition to causing gastrointestinal illnesses, some of these toxins are also carcinogenic and genotoxic. Efficient analytical strategies are needed for their monitoring in U.S. domestic and imported shellfish.ObjectiveIn the US, DSTs and AZAs are the only lipophilic shellfish toxins addressed in regulations. Streamlining of existing methods for several classes of lipophilic toxins, based on liquid chromatography coupled with triple quadrupole mass spectrometry, was pursued.MethodThe resulting simplified LC-MS/MS method is focused on the separation and detection of just the AZAs and total DSTs using a C18 Hypersil gold column. Filter vials are used to expedite and simplify sample handling.ResultsThe method has a run time of 7.25 min. LOQs for the AZAs and DSTs in shellfish were 0.3–0.4 µg/kg. Recoveries (AZAs and total DSTs) for three spiking levels in three matrixes ranged from 68 to 129%. Trueness was established using certified reference materials. Method equivalence was established using shellfish provided blind by the Washington State Department of Health Public Health Laboratory (WA DOH PHL). Data obtained from these samples agreed well with data from another LC-MS/MS method used in harvest control by WA DOH PHL (R = 0.999; P &lt; 0.0001).ConclusionsThe LC-MS/MS method described offers more rapid sample handling and has excellent sensitivity, linearity, and repeatability.
Perioperative therapies for urological cancers
Authors: Inokuchi Junichi , Yokomizo Akira , Nishiyama Naotaka , Kitamura Hiroshi , Eto Masatoshi , Nishiyama Hiroyuki , Tomita Yoshihiko 
Published: January 2020

Abstract
Although surgery with curative intent is critical for management of many localized cancers, multimodal therapy including neoadjuvant and adjuvant therapy has been introduced to increase the effectiveness of local control of surgery and prolong survival. However, strong evidence supporting the utility of such multimodal therapy is limited. The utility of perioperative chemotherapy has been extensively investigated in bladder cancer, and several randomized controlled trials have indicated the benefit of neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Regrettably, perioperative therapy for other urological cancers is controversial; therefore, no definitive conclusions have been drawn. Recently, the number of trials has rapidly increased due to the development of immune checkpoint inhibitors, used alone or in combination with other modalities. In this review, we summarize the current status and supporting evidence for perioperative therapies such as neoadjuvant and adjuvant therapies for urological cancers, including prostate cancer, urothelial cancer and renal cell carcinoma.
Government as Network Catalyst: Accelerating Self-Organization in a Strategic Industry
Authors: Whetsell Travis A , Siciliano Michael D , Witkowski Kaila G K , Leiblein Michael J 
Published: January 2020

AbstractGovernments have long-standing interests in preventing market failures and enhancing innovation in strategic industries. Public policy regarding domestic technology is critical to both national security and economic prosperity. Governments often seek to enhance their global competitiveness by promoting private sector cooperative activity at the inter-organizational level. Research on network governance has illuminated the structure of boundary-spanning collaboration mainly for programs with immediate public or nonprofit objectives. Far less research has examined how governments might accelerate private sector cooperation to prevent market failures or to enhance innovation. The theoretical contribution of this research is to suggest that government programs might catalyze cooperative activity by accelerating the preferential attachment mechanism inherent in social networks. We analyze the long-term effects of a government program on the strategic alliance network of 451 organizations in the high-tech semiconductor industry between 1987 and 1999, using stochastic network analysis methods for longitudinal social networks.