bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Systemic Influences on Data-Informed Learning: Document Review of Policies, Procedures, and Legislation from Canada and the United States
Authors: Wiljer David , Williams Spencer , Charow Rebecca , Campbell Craig , Davis Dave , Younus Sarah , Mylopoulos Maria , Okrainec Allan , Silver Ivan , Tavares Walter , Sockalingam Sanjeev 
Published: April 2022

Introduction:
Despite the support for and benefits of data-driven learning, physician engagement is variable. This study explores systemic influences of physician use of data for performance improvement in continuing professional development (CPD) by analyzing and interpreting data sources from organizational and institutional documents.

Methods:
The document analysis is the third phase of a mixed-methods explanatory sequential study examining cultural factors that influence data-informed learning. A gray literature search was conducted for organizations both in Canada and the United States. The analysis contains nonparticipant observations from professional learning bodies and medical specialty organizations with established roles within the CPD community known to lead and influence change in CPD.

Results:
Sixty-two documents were collected from 20 Canadian and American organizations. The content analysis identified the following: (1) a need to advocate for data-informed self-assessment and team-based learning strategies; (2) privacy and confidentiality concerns intersect at the point of patient data collection and physician-generated outcomes and need to be acknowledged; (3) a nuanced data strategy approach for each medical specialty is needed.

Discussion:
This analysis broadens our understanding of system-level factors that influence the extent to which health information custodians and physicians are motivated to engage with data for learning.
Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation
Authors: Kulkarni Sakil S. , Goss Charles W. , Khan Adeel S. , Nadler Michelle L. , Stoll Janis M. , Doyle Maria B. , Turmelle Yumirle P. , Rudnick David A. 
Published: April 2022

ABSTRACTBackground:We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database.Methods:Pediatric subjects listed for LT from 2002 to 2015 were assigned to the “PALF” group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the “non‐PALF” group if listed with any status other than 1/1A (N = 4509).Results:The PALF group had more infants <3 months of age and males at listing for LT compared to the non‐PALF group. Two‐thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non‐PALF group. Likelihood of removal from the LT waitlist for being “too sick” was higher, while that of removal for “spontaneous recovery” was lower in PALF subjects. Post‐LT short‐term (30 days) and long‐term (60 months) outcomes were also significantly worse in PALF versus non‐PALF subjects. PALF subjects who underwent living‐donor‐liver‐transplant (LDLT) had similar LT waitlist times and post‐LT survival compared to those undergoing deceased‐donor‐liver‐transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist‐ and short‐term post‐LT‐survival in PALF subjects.Conclusion:LT waitlist and post‐LT outcomes are worse in PALF subjects compared to non‐PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post‐LT outcomes compared to those undergoing DDLT.
Risk of Post‐Resection Recurrence in Pediatric Crohn Disease
Authors: Gray Ashley , Boyle Brendan , Michel Hilary K. , Wright Molly , Dotson Jennifer L. , Maltz Ross M. 
Published: April 2022

ABSTRACTBackground:Ileocecectomy related to stricturing, fistula formation, or medically refractory disease is commonly required in patients with Crohn disease (CD). Limited research exists in endoscopic recurrence (ER) in pediatric inflammatory bowel disease (IBD). In this study, we sought to determine ER rates and the impact of therapy duration before surgery in pediatric patients with CD.Methods:This was a single‐center retrospective review of patients with CD between the ages of 2 to 20 years who required ileocecectomy between January 2015 and December 2019 at Nationwide Children's Hospital. Follow‐up endoscopies, laboratory values, medications, and sPCDAI scores were recorded at 6, 12, 24, and 36 months post‐resection wherever available. Modified Rutgeert scores (mRS) were independently assigned to post‐resection colonoscopy images by 3 trained investigators. Post‐resection outcomes were compared between patients on CD therapy >30 days before resection (late surgery) to those started on CD therapy <30 days before resection (early surgery).Results:A total of 48 patients underwent ileocecectomy, with a mean age at time of resection of 17 years (+/−2.3). In total, 88% of patients had a post‐resection endoscopy and 57% had an endoscopy within 12 months of resection. Twenty‐nine percentage had ER with a mRS ≥i2. There was no statistical difference in endoscopic and clinical outcomes after resection between the early and late surgery groups.Conclusions:Post‐resection endoscopic recurrence after ileocecectomy was found in 29% of our center's pediatric CD population based on mRS. Post‐resection outcomes were not affected by therapy duration before resection.
Changes in Glucose Breath Test in Cystic Fibrosis Patients Treated With 1 Month of Lumacaftor/Ivacaftor
Authors: Gabel Megan E. , Wang Hongyue , Gelfond Daniel , Roach Christine , Rowe Steven M. , Clancy John P. , Sagel Scott D. , Borowitz Drucy ,   on behalf of the PROSPECT GIFT Sub-study Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network
Published: April 2022

Background:
Alteration of the airway microbiota is a hallmark of cystic fibrosis (CF) pulmonary disease. Dysfunction of cystic fibrosis transmembrane regulator (CFTR) in the intestine also promotes changes in local microbiota such as small intestinal bacterial overgrowth (SIBO), which is common in CF. We evaluated whether therapy with the CFTR modulator combination lumacaftor/ivacaftor (luma/iva) has a beneficial impact on SIBO as measured by breath testing (BT).

Methods:
A multicenter longitudinal study of CFTR-dependent disease profiling (NCT02477319) included a prospective evaluation for SIBO by BT. Tidal breath samples were collected after fasting and 15, 30, 45, 60, 90, and 120 minutes after ingestion of glucose, before and 1 month after subjects initiated luma + iva.

Results:
Forty-two subjects enrolled in the sub-study (mean age = 23.3 years; 51% female; 9.5% Latinx); 38 completed a hydrogen BT at both time points, of which 73.7% had a positive BT before luma/iva (baseline) and 65.8% had a positive test after luma/iva (P = 0.44); shifts from negative to positive were also seen. Use of azithromycin (63.1%) and inhaled antibiotics (60.5%) were not associated with positive BT. Acid-blocking medications were taken by 73% of those with a negative BT at baseline and by 35% with a positive baseline BT (P = 0.04).

Conclusion:
We found a high rate of positive hydrogen breath tests in individuals with CF, confirming that SIBO is common. One month of luma/iva did not significantly change the proportion of those with positive breath hydrogen measurements.
Patient and Caregivers’ Perspectives on Biosimilar Use in Pediatric Inflammatory Bowel Disease
Authors: Yossef Lina , Wright Molly , Benedict Jason , Morris Grant A. , McNicol Megan , Boyle Brendan , Dotson Jennifer L. , Michel Hilary K. , Maltz Ross M. 
Published: April 2022

Background:
Studies assessing adult inflammatory bowel disease (IBD) patient perspectives on biosimilar use revealed that most were unfamiliar with biosimilars and had a negative perception. The objective of this study was to evaluate the perspectives of pediatric patients with IBD and their caregivers regarding biosimilar use and non-medical switches.

Methods:
A survey was given to a cross section of patients with IBD ages 11–21 years receiving the intravenous anti-tumor necrosis factor originator and caregivers of patients with IBD ages 3–21 years receiving the originator. Recruitment occurred via mail, during clinic visits, and infusions. Fisher exact tests were used to test for statistically significant differences.

Results:
Response rate amongst caregivers was 49% (n = 98) and among patients was 35% (n = 67). Sixty-four percent of caregivers and 79% of patients had never heard of biosimilars. There was increased discomfort surrounding the use of biosimilars and switching to a biosimilar amongst caregivers who had previously heard of biosimilars compared to caregivers who had not previously heard of biosimilars (P < 0.05). Similar concerns were not seen in patient respondents. The length of time on the originator had no effect on patient or caregiver concerns related to biosimilar efficacy, adverse effects, or switches.

Conclusion:
The majority of pediatric patients and caregivers had never heard of biosimilars. Caregivers that had heard of biosimilars before the study were more likely to have a negative perception of them. This study highlights the importance of providing thorough and accurate education to pediatric patients and families regarding the safety and efficacy of biosimilars.
EURO-MUSCULUS/USPRM Dynamic Ultrasound Protocols for Wrist and Hand
Authors: Mezian Kamal , Ricci Vincenzo , Güvener Orhan , Jačisko Jakub , Novotný Tomáš , Kara Murat , Ata Ayşe Merve , Wu Wei-Ting , Chang Ke-Vin , Stecco Carla , Pirri Carmelo , Leblebicioğlu Gürsel , Özçakar Levent 
Published: April 2022

ABSTRACT
In this dynamic protocol, ultrasound evaluation of the wrist and hand is described using various maneuvers for relevant conditions. Scanning videos are coupled with real-time patient examination videos. The authors believe that this practical guide - prepared by the international consensus of several experts - will help musculoskeletal physicians perform a better and uniform/standard examination approach.
Development and Usability Testing of the Agency for Healthcare Research and Quality Common Formats to Capture Diagnostic Safety Events
Authors: Bradford Andrea , Shahid Umber , Schiff Gordon D. , Graber Mark L. , Marinez Abigail , DiStabile Paula , Timashenka Andrea , Jalal Hamid , Brady P. Jeffrey , Singh Hardeep 
Published: April 2022

Objectives
A lack of consensus around definitions and reporting standards for diagnostic errors limits the extent to which healthcare organizations can aggregate, analyze, share, and learn from these events. In response to this problem, the Agency for Healthcare Research and Quality (AHRQ) began the development of the Common Formats for Event Reporting for Diagnostic Safety Events (CFER-DS). We conducted a usability assessment of the draft CFER-DS to inform future revision and implementation.

Methods
We recruited a purposive sample of quality and safety personnel working in 8 U.S. healthcare organizations. Participants were invited to use the CFER-DS to simulate reporting for a minimum of 5 cases of diagnostic safety events and then provide written and verbal qualitative feedback. Analysis focused on participants’ perceptions of content validity, ease of use, and potential for implementation.

Results
Estimated completion time was 30 to 90 minutes per event. Participants shared generally positive feedback about content coverage and item clarity but identified reporter burden as a potential concern. Participants also identified opportunities to clarify several conceptual definitions, ensure applicability across different care settings, and develop guidance to operationalize use of CFER-DS. Findings led to refinement of content and supplementary materials to facilitate implementation.

Conclusions
Standardized definitions of diagnostic safety events and reporting standards for contextual information and contributing factors can help capture and analyze diagnostic safety events. In addition to usability testing, additional feedback from the field will ensure that AHRQ’s CFER-DS is useful to a broad range of users for learning and safety improvement.
How informal healthcare providers improve uptake of HIV testing: qualitative results from a randomized controlled trial
Authors: Ponticiello Matthew , Mwanga-Amumpaire Juliet , Tushemereirwe Patricia , Nuwagaba Gabriel , Nansera Denis , King Rachel , Muyindike Winnie , Sundararajan Radhika 
Published: April 2022

Objective:
Uganda is HIV-endemic with a prevalence of 5.7%. Lack of epidemic control has been attributed to low engagement with HIV testing. Collaborating with informal healthcare providers, such as traditional healers, has been proposed as a strategy to increase testing uptake. We explored acceptability and implementation of an HIV testing program where traditional healers delivered point-of-care testing and counseling to adults of unknown serostatus (clinicaltrials.gov NCT#03718871).

Methods:
This study was conducted in rural, southwestern Uganda. We interviewed participating traditional healers (N = 17) and a purposive sample of trial participants (N = 107). Healers were practicing within 10 km of Mbarara township, and 18+ years old. Participants were 18+ years old; sexually active; had received care from participating healers; self-reported not receiving an HIV test in prior 12 months; and not previously diagnosed with HIV infection. Interviews explored perceptions of a healer-delivered HIV testing model and were analyzed following a content-analysis approach.

Results:
Most participants were female individuals (N = 68, 55%). Healer-delivered HIV testing overcame structural barriers, such as underlying poverty and rural locations that limited use, as transportation was costly and often prohibitive. Additionally, healers were located in villages and communities, which made services more accessible compared with facility-based testing. Participants also considered healers trustworthy and ‘confidential’. These qualities explain some preference for healer-delivered HIV testing, in contrast to ‘stigmatizing’ biomedical settings.

Conclusion:
Traditional healer-delivered HIV testing was considered more confidential and easily accessible compared with clinic-based testing. Offering services through traditional healers may improve uptake of HIV testing services in rural, medically pluralistic communities.
Coordination of inflammatory responses in children with perinatally acquired HIV infection
Authors: Weinberg Adriana , Giganti Mark J. , Sirois Patricia A. , Montepiedra Grace , Canniff Jennifer , Agwu Allison , Boivin Michael J. , Kapetanovic Suad , Abzug Mark J. ,   for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network
Published: April 2022

Objective:
We investigated dynamics of inflammatory biomarkers in children with perinatally acquired HIV (PHIV) who started antiretrovirals at age less than 3 years and achieved sustained virologic control (HIV plasma RNA <400 copies/ml).

Design:
This was a retrospective analysis of inflammatory biomarkers in children enrolled in a randomized trial of early (<3 years of age) PI-based versus NNRTI-based regimens (P1060), who achieved sustained virologic control and participated in a neurodevelopmental follow-up study (P1104s) between ages 5 and 11 years.

Methods:
We measured 20 inflammatory biomarkers using ELISA or chemiluminescence at onset of sustained virologic control (Tc) and at P1104s entry (Te).

Results:
The 213 participants had median ages of 1.2, 1.9, and 7 years at antiretroviral initiation, Tc, and Te, respectively, with 138 on protease inhibitor-based and 74 on NNRTI-based regimens at Tc. Eighteen markers decreased and two increased from Tc to Te (Te-Tc). Biomarker subsets, particularly cytokines, the chemokine IP-10, and adhesion molecules sICAM-1 and sVCAM-1, correlated at Tc, Te, and Te-Tc. At Tc, higher biomarker levels were associated with younger age, female sex, HIV plasma RNA at least 750 000 copies/ml, lower nadir CD4+%, lower nadir weight z scores, and NNRTI-based treatment. Greater Te-Tc biomarker declines were associated with younger age, male sex, higher Tc biomarker levels, lower nadir CD4+%, and NNRTI-based treatment. Duration of controlled viremia and nadir height z scores showed mixed associations.

Conclusion:
Biomarker expression showed substantial coordination. Most markers decreased after virologic control. Demographic and clinical variables associated with biomarker patterns were identified. Mechanistic studies of these biomarker patterns are needed to inform interventions to control inflammation.
Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy
Authors: Levi Laura I. , Sharma Shweta , Schleiss Mark R. , Furrer Hansjakob , Nixon Daniel E. , Blackstad Mark , Hernandez-Alvarado Nelmary , Dwyer Dominic E. , Borges Alvaro H. , Lane H. Clifford , Lundgren Jens , Neaton James D. , Molina Jean-Michel 
Published: April 2022

Objective:
To assess the prevalence of CMV viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes.

Design:
Retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB).

Methods:
Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through one year of follow-up after ART initiation. CMV viremia was measured centrally using a quantitative PCR assay. Within FIRST, associations of CMV viremia at baseline and through eight months of ART were examined with a composite clinical outcome of AIDS, serious non-AIDS events, or death using Cox proportional hazards regression.

Results:
Samples from a total of 3176 participants, 1169 from FIRST, 137 from ANRS REFLATE TB, 54 from SMART, and 1816 from START were available with baseline CMV viremia prevalence of 17%, 26%, 0% and 1%, respectively. Pooled across trials, baseline CMV viremia was associated with low CD4+ T-cell counts and high HIV RNA levels. In FIRST, CMV viremia was detected in only 5% of participants between baseline and month 8. After adjustment for CD4+ T-cell count and HIV RNA levels, hazard ratios (HR) for risk of clinical outcomes was 1.15 (0.86–1.54) and 2.58 (1.68 – 3.98) in FIRST participants with baseline and follow-up CMV viremia, respectively.

Conclusion:
Baseline CMV viremia in HIV-positive patients starting ART is associated with advanced infection and only persistent CMV viremia after ART initiation is associated with a higher risk of morbidity and mortality.
Decentralized Distributed Multi-institutional PET Image Segmentation Using a Federated Deep Learning Framework
Authors: Shiri Isaac , Vafaei Sadr Alireza , Amini Mehdi , Salimi Yazdan , Sanaat Amirhossein , Akhavanallaf Azadeh , Razeghi Behrooz , Ferdowsi Sohrab , Saberi Abdollah , Arabi Hossein , Becker Minerva , Voloshynovskiy Slava , Gündüz Deniz , Rahmim Arman , Zaidi Habib 
Published: April 2022

Purpose
The generalizability and trustworthiness of deep learning (DL)–based algorithms depend on the size and heterogeneity of training datasets. However, because of patient privacy concerns and ethical and legal issues, sharing medical images between different centers is restricted. Our objective is to build a federated DL-based framework for PET image segmentation utilizing a multicentric dataset and to compare its performance with the centralized DL approach.

Methods
PET images from 405 head and neck cancer patients from 9 different centers formed the basis of this study. All tumors were segmented manually. PET images converted to SUV maps were resampled to isotropic voxels (3 × 3 × 3 mm3) and then normalized. PET image subvolumes (12 × 12 × 12 cm3) consisting of whole tumors and background were analyzed. Data from each center were divided into train/validation (80% of patients) and test sets (20% of patients). The modified R2U-Net was used as core DL model. A parallel federated DL model was developed and compared with the centralized approach where the data sets are pooled to one server. Segmentation metrics, including Dice similarity and Jaccard coefficients, percent relative errors (RE%) of SUVpeak, SUVmean, SUVmedian, SUVmax, metabolic tumor volume, and total lesion glycolysis were computed and compared with manual delineations.

Results
The performance of the centralized versus federated DL methods was nearly identical for segmentation metrics: Dice (0.84 ± 0.06 vs 0.84 ± 0.05) and Jaccard (0.73 ± 0.08 vs 0.73 ± 0.07). For quantitative PET parameters, we obtained comparable RE% for SUVmean (6.43% ± 4.72% vs 6.61% ± 5.42%), metabolic tumor volume (12.2% ± 16.2% vs 12.1% ± 15.89%), and total lesion glycolysis (6.93% ± 9.6% vs 7.07% ± 9.85%) and negligible RE% for SUVmax and SUVpeak. No significant differences in performance (P > 0.05) between the 2 frameworks (centralized vs federated) were observed.

Conclusion
The developed federated DL model achieved comparable quantitative performance with respect to the centralized DL model. Federated DL models could provide robust and generalizable segmentation, while addressing patient privacy and legal and ethical issues in clinical data sharing.
Urinary Bladder Matrix Improves Irradiated Wound Healing in a Murine Model
Authors: Yao Jingxin , Vangsness Kella L. , Khim Phillip , Raghuram Anjali C. , Park Sun Young , Yu Roy , Wang Jin , Jiao Wan , Wong Alex K. 
Published: April 2022

Abstract
Radiation skin damage is associated with chronic wounds and poor healing. Existing localized treatment modalities have limited benefit. Therefore, there has been increased interest in biologically based solutions. In this study, we aimed to determine the effect of topical urinary bladder matrix (UBM) on chronic irradiated skin wounds using an established murine model. Our findings demonstrated that topical urinary bladder matrix significantly accelerated the healing of irradiated wounds on day 7 (P = 0.0216), day 14 (P = 0.0140), and day 21 (P = 0.0393). Histologically, urinary bladder matrix treatment was associated with higher-quality reorganization and reepithelialization of wounds, an increased density of myofibroblasts (P = 0.0004), and increased collagen deposition (P < 0.0001). In addition, quantitative real-time polymerase chain reaction data demonstrated decreased expression of profibrotic mediators (P = 0.0049). We conclude that urinary bladder matrix may be a useful, noninvasive, adjunctive therapy for the treatment of chronic irradiated skin wounds.