bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of first‐line infliximab on the pharmacokinetics of second‐line vedolizumab in inflammatory bowel diseases
Authors: Liefferinckx Claire , Verstockt Bram , Gils Ann , Tops Sophie , Van Moerkercke Wouter , Vermeire Severine , Franchimont Denis 
Published: March 2019

BackgroundVery little is known about the impact of the wash‐out period on the pharmacokinetics of a second‐line biologic.ObjectiveThe objective of this article is to explore the impact of two different wash‐out periods on the pharmacokinetics of vedolizumab and infliximab.MethodsPatients switching from infliximab to vedolizumab were retrospectively identified. The population was divided into two groups according to wash‐out period: <6 weeks or >6 weeks. Vedolizumab and infliximab trough levels (TLs) were determined and correlated with clinical and biological outcomes.ResultsA total of 71 inflammatory bowel disease patients were included. At week 6, in patients previously treated with infliximab, median vedolizumab TLs were 21.9 µg/ml and 24.9 µg/ml for the <6 weeks and >6 weeks wash‐out period, respectively (p = 0.31), whereas median residual infliximab TLs were 0.5 µg/ml and 0 µg/ml (p = 0.034). The rate of treatment discontinuation was similar (p = 0.64), and the infectious events were six and two for the <6 weeks and >6 weeks wash‐out period, respectively (p = 0.12) by week 30.ConclusionsThis study suggests clinicians may not need to be concerned about the impact of wash‐out period on the pharmacokinetics of the second‐line biologic when switching infliximab to vedolizumab. More data are required on the impact of wash‐out period on safety.
Prolonged QTc in HIV-Infected Patients: A Need for Routine ECG Screening
Authors: Myerson Merle , Kaplan-Lewis Emma , Poltavskiy Eduard , Ferris David , Bang Heejung 
Published: March 2019

Background: With HIV-infected patients living longer, there is an increased burden of comorbidities related to aging, HIV itself, and polypharmacy. Cardiac morbidity is of particular importance. Methods: This 2-group comparison study (156 HIV-positive and 105 HIV-negative patients) investigated the prevalence of abnormalities in and factors associated with an electrocardiogram (ECG) measure, corrected QT interval (QTc), where prolongation can lead to arrhythmia and sudden death. Medications prescribed (antiretroviral therapy, psychiatric medications, methadone, and antibiotics) at the time of ECG were noted. Patient characteristics, medications, QTc, and ECG characteristics were compared between the 2 groups. Results: Prolongation (29% versus 19%) and extreme prolongation (6% versus 1%) in QTc were more frequent in those with HIV. Antiretroviral therapy was associated with lower odds of prolonged QTc (odds ratio [OR] = 0.35; P = .04), while methadone with higher odds (OR = 4.6; P = .01) in HIV-positive patients. With methadone and medication groups adjusted, HIV status was still associated with 17-millisecond longer QTc ( P = .04). Conclusion: This study provides evidence that patients with HIV may have clinically relevant longer QTc interval on ECG. Baseline and routine ECG monitoring may be warranted among patients living with HIV in clinical practice based on cumulative evidence.
Defining Learning Communities in Undergraduate Medical Education: A National Study
Authors: Shochet Robert , Fleming Amy , Wagner James , Colbert-Getz Jorie , Bhutiani Monica , Moynahan Kevin , Keeley Meg 
Published: March 2019

Background: Learning communities (LCs) are intentionally designed groups that are actively engaged in learning with and from each other. While gaining prominence in US medical schools, LCs show significant variability in their characteristics across institutions, creating uncertainty about how best to measure their effects. Objective: The aim of this study is to describe the characteristics of medical school LCs by primary purpose, structures, and processes and lay the groundwork for future outcome studies and benchmarking for best practices. Methods: Medical school LC directors from programs affiliated with the Learning Communities Institute (LCI) were sent an online survey of program demographics and activities, and asked to upload a program description or summary of the LC’s purpose, goals, and how it functions. Descriptive statistics were computed for survey responses and a qualitative content analysis was performed on program descriptions by 3 authors to identify and categorize emergent themes. Results: Of 28 medical school LCs surveyed, 96% (27) responded, and 25 (89%) provided program descriptions for qualitative content analysis. All programs reported longitudinal relationships between students and faculty. Most frequently cited objectives were advising or mentoring (100%), professional development (96%), courses (96%), social activities (85%), and wellness (82%). Primary purpose themes were supporting students’ professional development, fostering a sense of community, and creating a sense of wholeness. Structures included a community framework, subdivisions into smaller units, and governance by faculty and students. Process themes included longitudinal relationships, integrating faculty roles, and connecting students across class years. Conclusions: Medical school LCs represent a collection of high-impact educational practices characterized by community and small-group structures, relational continuity, and collaborative learning as a means to guide and holistically support students in their learning and development as physicians. In describing 27 medical school LCs, this study proposes a unifying framework to facilitate future educational outcomes studies across institutions.
Quality Improvement Initiative to Improve Tobacco Cessation Efforts in Radiation Oncology
Authors: Singer Lisa , Sharee Keith , Boreta Lauren , Silveira William R. , Braunstein Steve , Fogh Shannon 
Published: March 2019

PURPOSE: Although continued tobacco use in patients who are treated with radiation therapy is associated with inferior outcomes and increased treatment-related toxicity, multiple studies have shown that current tobacco cessation efforts in oncology are insufficient. A quality improvement (QI) initiative was developed with the goal of improving tobacco cessation efforts in radiation oncology. METHODS: Using iterative plan-do-study-act cycles, barriers to tobacco cessation were identified and then addressed with a single-institutional QI initiative designed to improve physician assessment of patient readiness to quit tobacco by 50% or more. Residents assessed readiness to quit tobacco during new patient consultations and recorded this assessment in prespecified fields within the electronic health record. Feedback on assessment efforts was provided to our department via an automated search of the electronic health record. RESULTS: From December 2014 to February 2015, before the initiation of the QI initiative, 4% of patients were assessed for their readiness to quit tobacco. After implementing the initiative, 67% of patients were assessed for their readiness to quit. CONCLUSION: After instituting a QI initiative at our institution, significantly more patients were assessed for readiness to quit tobacco before treatment with radiation therapy. Ongoing efforts in our department are aimed at improving the efficacy of this intervention.
Models of Outpatient Palliative Care Clinics for Patients With Cancer
Authors: Finlay Esme , Newport Kristina , Sivendran Shanthi , Kilpatrick Laurel , Owens Michelle , Buss Mary K. 
Published: March 2019

PURPOSE:Early integration of outpatient palliative care (OPC) benefits patients with advanced cancer and also the health care systems in which these patients are seen. Successful development and implementation of models of OPC require attention to the needs and values of both the patients being served and the institution providing service.SUMMARY:In the 2016 clinical guideline, ASCO recommended integrating palliative care early in the disease trajectory alongside cancer-directed treatment. Despite strong endorsement and robust evidence of benefit, many patients with cancer lack access to OPC. Here we define different models of care delivery in four successful palliative care clinics in four distinct health care settings: an academic medical center, a safety net hospital, a community health system, and a hospice-staffed clinic embedded in a community cancer center. The description of each clinic includes details on setting, staffing, volume, policies, and processes.CONCLUSION:The development of robust and capable OPC clinics is necessary to meet the growing demand for these services among patients with advanced cancer. This summary of key aspects of functional OPC clinics will enable health care institutions to evaluate their specific needs and develop programs that will be successful within the environment of an individual institution.
Ability of an Arterial Waveform Analysis–Derived Hypotension Prediction Index to Predict Future Hypotensive Events in Surgical Patients
Authors: Davies Simon James , Vistisen Simon Tilma , Jian Zhongping , Hatib Feras , Scheeren Thomas W. L. 
Published: March 2019

BACKGROUND:
Intraoperative hypotension is associated with worse perioperative outcomes for patients undergoing major noncardiac surgery. The Hypotension Prediction Index is a unitless number that is derived from an arterial pressure waveform trace, and as the number increases, the risk of hypotension occurring in the near future increases. We investigated the diagnostic ability of the Hypotension Prediction Index in predicting impending intraoperative hypotension in comparison to other commonly collected perioperative hemodynamic variables.

METHODS:
This is a 2-center retrospective analysis of patients undergoing major surgery. Data were downloaded and analyzed from the Edwards Lifesciences EV1000 platform. Receiver operating characteristic curves were constructed for the Hypotension Prediction Index and other hemodynamic variables as well as event rates and time to event.

RESULTS:
Two hundred fifty-five patients undergoing major surgery were included in the analysis yielding 292,025 data points. The Hypotension Prediction Index predicted hypotension with a sensitivity and specificity of 85.8% (95% CI, 85.8%–85.9%) and 85.8% (95% CI, 85.8%–85.9%) 5 minutes before a hypotensive event (area under the curve, 0.926 [95% CI, 0.925–0.926]); 81.7% (95% CI, 81.6%–81.8%) and 81.7% (95% CI, 81.6%–81.8%) 10 minutes before a hypotensive event (area under the curve, 0.895 [95% CI, 0.894–0.895]); and 80.6% (95% CI, 80.5%–80.7%) and 80.6% (95% CI, 80.5%–80.7%) 15 minutes before a hypotensive event (area under the curve, 0.879 [95% CI, 0.879–0.880]). The Hypotension Prediction Index performed superior to all other measured hemodynamic variables including mean arterial pressure and change in mean arterial pressure over a 3-minute window.

CONCLUSIONS:
The Hypotension Prediction Index provides an accurate real time and continuous prediction of impending intraoperative hypotension before its occurrence and has superior predictive ability than the commonly measured perioperative hemodynamic variables.
fs(1)h controls metabolic and immune function and enhances survival via AKT and FOXO in Drosophila
Authors: Sharrock Jessica , Estacio-Gomez Alicia , Jacobson Jake , Kierdorf Katrin , Southall Tony D. , Dionne Marc S. 
Published: March 2019

ABSTRACT
The Drosophila fat body is the primary organ of energy storage as well as being responsible for the humoral response to infection. Its physiological function is of critical importance to the survival of the organism; however, many molecular regulators of its function remain ill-defined. Here, we show that the Drosophila melanogaster bromodomain-containing protein FS(1)H is required in the fat body for normal lifespan as well as metabolic and immune homeostasis. Flies lacking fat body fs(1)h exhibit short lifespan, increased expression of immune target genes, an inability to metabolize triglyceride, and low basal AKT activity, mostly resulting from systemic defects in insulin signalling. Removal of a single copy of the AKT-responsive transcription factor foxo normalises lifespan, metabolic function, uninduced immune gene expression and AKT activity. We suggest that the promotion of systemic insulin signalling activity is a key in vivo function of fat body fs(1)h.
This article has an associated First Person interview with the first author of the paper.
New quantitative approach reveals heterogeneity in mitochondrial structure–function relations in tumor-initiating cells
Authors: Spurlock Brian , Gupta Priyanka , Basu Malay Kumar , Mukherjee Avik , Hjelmeland Anita B. , Darley-Usmar Victor , Parker Danitra , Foxall McKenzie E. , Mitra Kasturi 
Published: March 2019

ABSTRACT
Steady-state mitochondrial structure or morphology is primarily maintained by a balance of opposing fission and fusion events between individual mitochondria, which is collectively referred to as mitochondrial dynamics. The details of the bidirectional relationship between the status of mitochondrial dynamics (structure) and energetics (function) require methods to integrate these mitochondrial aspects. To study the quantitative relationship between the status of mitochondrial dynamics (fission, fusion, matrix continuity and diameter) and energetics (ATP and redox), we have developed an analytical approach called mito-SinCe2. After validating and providing proof of principle, we applied mito-SinCe2 on ovarian tumor-initiating cells (ovTICs). Mito-SinCe2 analyses led to the hypothesis that mitochondria-dependent ovTICs interconvert between three states, that have distinct relationships between mitochondrial energetics and dynamics. Interestingly, fusion and ATP increase linearly with each other only once a certain level of fusion is attained. Moreover, mitochondrial dynamics status changes linearly with ATP or with redox, but not simultaneously with both. Furthermore, mito-SinCe2 analyses can potentially predict new quantitative features of the opposing fission versus fusion relationship and classify cells into functional classes based on their mito-SinCe2 states.
This article has an associated First Person interview with the first author of the paper.
Distribution of Toxoplasma gondii IgM and IgG antibody seropositivity among age groups and gestational periods in pregnant women
Authors: Sadiqui Shahida , Shah Syed Rafiq Hussain , Almugadam Babiker Saad , Shakeela Qismat , Ahmad Shehzad 
Published: March 2019

Background: Toxoplasmosis is a globally distributed parasitic disease. The present study aimed to estimate the prevalence and geographic distribution of toxoplasmosis as well as evaluate the role of animal contact in disease development and determine the percentage of toxoplasmosis-associated IgM and IgG seropositivity among different age groups. In addition, it aimed to estimate the proportion of toxoplasma IgM seropositivity among pregnancy trimesters. Methods: A total of 500 pregnant women were included in this study. From each participant, a 5-ml venous blood sample was collected and centrifuged to obtain serum that was tested for Toxoplasma gondii IgM and IgG antibodies using immunochromatographic testing and ELISA. Results: The overall seroprevalence of toxoplasmosis was 24.8%, with rates of acute infection of 8%. Among positive cases of every trimester, 54.34% of first trimester positive cases had a serologic marker for acute toxoplasmosis. Among the overall positive cases, out of the 35 pregnant women with previous history of cow/buffalo contact and toxoplasmosis, 45.7% were seropositive for toxoplasma IgM; and out of 15 women with prior history of dog contact, 33.3% had a serological marker of acute toxoplasmosis. Conclusions: In this study, there is a high prevalence of toxoplasmosis and contact with domestic animals is a risk factor of this illness. Therefore, it is necessary to test every pregnant woman for toxoplasmosis and distinguish the type of infection, as well as the conduction of public health education programs to generate the awareness.
Lifting the fog in intermediate-risk (submassive) PE: full dose, low dose, or no thrombolysis?
Authors: Bhamani Amyn , Pepke-Zaba Joanna , Sheares Karen 
Published: March 2019

Acute pulmonary embolism (PE) is a disease frequently encountered in clinical practice. While the management of haemodynamically stable, low risk patients with acute PE is well established, managing intermediate disease often presents a therapeutic dilemma. In this review, we discuss the various therapeutic options available in this patient group. This includes thrombolysis, surgical embolectomy and catheter directed techniques. We have also explored the role of specialist PE response teams in the management of such patients. ​
A multinational evaluation assessing the relationship between peristomal skin health and health utility
Authors: Nichols Thomas , Goldstine Jimena , Inglese Gary 
Published: March 2019

Background: irritation to peristomal skin remains one of the most prevalent ostomy-related complications influencing an individual's health status and quality of life. Aims: to assess the impact of damaged peristomal skin on the health utility and quality-adjusted life days (QALD) in an international adult ostomy population. Methods: a cross-sectional survey incorporating the SF-6D preference-based health utility index was developed to assess a random selection of post-surgical patients. Findings: health utility decreased with increasing skin irritation among the three geographic groups. The total mean health utility of normal peristomal skin for the three groups dropped incrementally for mild, moderate, and severe irritation. There were no differences in health utility or QALDs between the three country groups. Conclusion: improvement of peristomal skin health is associated with improvements to QALDs. Clinicians, caregivers and patients have the responsibility to address a critical unmet need in skin health through interventions and products designed to support healthy peristomal skin.
Autologous Skin-Grafting Surgery to Prevent Esophageal Stenosis After Complete Circular Endoscopic Submucosal Tunnel Dissection for Superficial Esophageal Neoplasms
Authors: Chai Ningli , Zou Jiale , Linghu Enqiang , Chai Mi , Li Longsong , Wang Xiangyao , Zhang Wengang , Xiang Jingyuan , Li Zhenjuan 
Published: March 2019

OBJECTIVES:
To assess the safety and effectiveness of autologous skin-grafting surgery (ASGS) for preventing esophageal stenosis after complete circular endoscopic submucosal tunnel dissection (ccESTD) for superficial esophageal neoplasms.

METHODS:
Between October 2017 and March 2018, 8 patients who underwent ccESTD and ASGS were included. We assessed the occurrence of esophageal stenosis and adverse events.

RESULTS:
No adverse events occurred, including perforation, bleeding, wound infection, or stent migration. Five patients did not experience stenosis over a median follow-up of 7 months.

CONCLUSIONS:
ASGS appeared to be a safe and effective way to prevent esophageal stenosis after ccESTD.
Exposure to Vedolizumab in IBD Pregnant Women Appears of Low Risk for Mother and Neonate: A First Prospective Comparison Study
Authors: Bar-Gil Shitrit Ariella , Ben Ya'acov Ami , Livovsky Dan Meir , Cuker Tzufit , Farkash Rivka , Hoyda Aviya , Granot Tami , Avni-Biron Irit , Lahat Adi , Goldin Eran , Grisaru-Granovsky Sorina 
Published: March 2019

OBJECTIVES:
Despite encouraging data gathered in inflammatory bowel diseases (IBD) patients, Vedolizumabs' (VDZ) safety profile in pregnancy is not established.

DESIGN:
Data of 330 consecutive pregnancies with IBD was prospectively collected.

RESULTS:
Women with IBD were treated with: VDZ (n = 24), anti-tumor necrosis factors (n = 82) or conventional therapy (n = 224). Gravidity and parity were similar among the 3 groups. The VDZ group was comprised mostly of Crohn's disease patients who were all not naïve to biological treatment. They had significantly higher conception rates during active disease (P < 0.05), with fewer flares during pregnancy.

DISCUSSION:
Although further study is needed, VDZ appears of low risk during pregnancy.
Safety of Endoscopy in Heritable Connective Tissue Disorders
Authors: Kilaru Saikiran M. , Mukamal Kenneth J. , Nee Judy W. , Oza Sveta S. , Lembo Anthony J. , Wolf Jacqueline L. 
Published: March 2019

Introduction:
Little is known about the gastrointestinal manifestations or safety of endoscopy among patients with heritable connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome (EDS).

Methods:
We conducted an electronic cross-sectional survey nested within preexisting registries of patients with heritable connective tissue disorders and examined self-reported rates of endoscopic complications.

Results:
The rate of endoscopy-related perforation was 9.4% (95% confidence interval 2.0%–25.0%) among individuals with vascular EDS, <1% in classical and hypermobility-type EDS, and zero in Marfan syndrome (P < 0.001). Spontaneous intestinal perforation was also significantly higher in the vascular EDS group.

DISCUSSION:
Clinicians should consider noninvasive screening methods for patients with vascular EDS.
Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis
Authors: Bajaj Jasmohan S. , Hays R. Ann 
Published: March 2019

Abstract
Alteration of the normal gut-liver axis is important in primary sclerosing cholangitis (PSC). Lack of effective medical therapy for PSC makes microbiome restoration an alluring therapeutic target. Allegretti et al. performed an open-label safety trial of fecal microbiota transplant (FMT) in noncirrhotic PSC patients with inflammatory bowel disease in remission on minimal therapy. FMT was safe in this population, and after FMT, there was a stable, early increase in microbial diversity and donor engraftment with mixed effects on alkaline phosphatase but no significant change in fecal bile acid profile. Further trials are needed to find whether FMT has a role to play in PSC therapy.
Combined Endoscopic Fistulotomy and Clipping for the Treatment of Fistula From the Tip of the J-Pouch to Anastomosis
Authors: Sze Grace , Khan Freeha , Shen Bo 
Published: March 2019

ABSTRACT
Patients who undergo restorative protocolectomy with ileal pouch-anal anastomosis may develop mechanical complications such as presacral sinuses and fistulas. The current method of treatment may include medical therapy or redo surgery. Recently, endoscopic management for postoperative complications has shown effective results. We present a unique case of a pouch-to-pouch fistula, from the tip of the “J” to the anastomosis that was successfully treated with endoscopic needle-knife sinusotomy and over-the-scope clips.