bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches and strategies to manage the hepatitis C virus-positive heart donor
Authors: Lampert Brent C. , Kissling Kevin 
Published: June 2022

Purpose of review
Cardiac transplantation remains the treatment of choice for patients with advanced heart failure, but is limited by a donor organ shortage. Utilization of hepatitis C virus (HCV)-positive donors has been recently adopted to expand access to heart transplantation. We review the history of HCV heart transplantation, modern drug therapy, and recent outcomes.

Recent findings
Since the advent of direct-acting antiviral (DAA) therapy, several single-center studies, and retrospective reviews have demonstrated good short-term outcomes, shorter waitlist times, and clearance of viremia with recipients of HCV-positive hearts. Two principle approaches to treatment of recipients of HCV viremic donors are utilized. In the prophylactic strategy, therapy is initiated before viremia is detected compared with the preemptive approach where initiation of DAA is delayed until after viremia is detected. Future studies are needed to address uncertainty about medium and long-term outcomes of using HCV-positive hearts and to determine the optimal treatment timing and duration.

Summary
Utilization of HCV-positive donors has expanded the heart donor pool and appears safe through the early posttransplant period. We suggest that prophylactic administration of the shortest effective course of a DAA pangenotypic agent should be the current standard of care.
Gastrointestinal Features of 22q11.2 Deletion Syndrome Include Chronic Motility Problems From Childhood to Adulthood
Authors: Kotcher Rebecca E. , Chait Daniel B. , Heckert Jason M. , Crowley T. Blaine , Forde Kimberly A. , Ahuja Nitin K. , Mascarenhas Maria R. , Emanuel Beverly S. , Zackai Elaine H. , McDonald-McGinn Donna M. , Reynolds James C. 
Published: June 2022

Objectives:
22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS.

Methods:
All patients followed in the 22q and You Center at the Children’s Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed.

Results:
Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities (P < 0.01) but not with deletion size or physiologic comorbidities (P > 0.05). One exception was increased nausea/vomiting in hypothyroidism (P = 0.002).

Conclusions:
Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.
Novel Pediatric Height Outlier Detection Methodology for Electronic Health Records via Machine Learning With Monotonic Bayesian Additive Regression Trees
Authors: Sparapani Rodney A. , Teng Bi Q. , Hilbrands Julia , Pipkorn Rebecca , Feuling Mary Beth , Goday Praveen S. 
Published: June 2022

Objective:
To create a new methodology that has a single simple rule to identify height outliers in the electronic health records (EHR) of children.

Methods:
We constructed 2 independent cohorts of children 2 to 8 years old to train and validate a model predicting heights from age, gender, race and weight with monotonic Bayesian additive regression trees. The training cohort consisted of 1376 children where outliers were unknown. The testing cohort consisted of 318 patients that were manually reviewed retrospectively to identify height outliers.

Results:
The amount of variation explained in height values by our model, R
2, was 82.2% and 75.3% in the training and testing cohorts, respectively. The discriminatory ability to assess height outliers in the testing cohort as assessed by the area under the receiver operating characteristic curve was excellent, 0.841. Based on a relatively aggressive cutoff of 0.075, the outlier sensitivity is 0.713, the specificity 0.793; the positive predictive value 0.615 and the negative predictive value is 0.856.

Conclusions:
We have developed a new reliable, largely automated, outlier detection method which is applicable to the identification of height outliers in the pediatric EHR. This methodology can be applied to assess the veracity of height measurements ensuring reliable indices of body proportionality such as body mass index.
Maintenance Therapy for Preventing Endometrioma Recurrence After Endometriosis Resection Surgery—A Systematic Review and Network Meta-analysis
Authors: Chiu Chui-Ching , Hsu Teh-Fu , Jiang Ling-Yu , Chan I-San , Shih Ying-Chu , Chang Yen-Hou , Wang Peng-Hui , Chen Yi-Jen 
Published: June 2022

(Abstracted from J Minim Invasive Gynecol 2022;29:602–612)
Endometriosis is one of the most common gynecologic disorders, affecting approximately 10% of reproductive-age women and presenting with dysmenorrhea, noncyclic pelvic pain, dyspareunia, and infertility. Approximately 17% to 55% of women with endometriosis will also develop an endometrioma, which is usually an advanced disease stage of endometriosis.
Do New Trauma Centers Provide Needed or Redundant Access? A Nationwide Analysis
Authors: Ferre Alexandra C. , Curtis Jacqueline , Flippin J. Alford , Claridge Jeffrey A. , Tseng Esther S. , Brown Laura R. , Ho Vanessa P. 
Published: June 2022

Abstract

Background
Our prior research has demonstrated that increasing the number of trauma centers (TCs) in a state does not reliably improve state-level injury-related mortality. We hypothesized that many new TCs would serve populations already served by existing TCs, rather than in areas without ready TC access. We also hypothesized that new TCs would also be less likely to serve economically disadvantaged populations.

Methods
All state-designated adult TCs registered with the American Trauma Society in 2014 and 2019 were mapped using ArcGIS Pro. TCs were grouped as Level 1-2 (Lev12) or level 3-5 (Lev345). We also obtained census tract-level data (73,666 tracts), including population counts and % of population below the federal poverty threshold. Thirty-minute drive-time areas were created around each TC. Census tracts were considered “served” if their geographic centers were located within a 30-minute drive-time area to any TC. Data were analyzed at the census tract-level.

Results
2140 TCs were identified in 2019, with 256 new TCs and 151 TC closures. 82% of new TC were Level 3-5. Nationwide, coverage increased from 75.3% of tracts served in 2014 to 78.1% in 2019, representing an increased coverage from 76.0% to 79.4% of the population. New TC served 17,532 tracts, of which 87.3% were already served. New Lev12 TCs served 9,100 tracts, of which 91.2% were already served; New Lev345 TCs served 15,728 tracts, of which 85.9% were already served. Of 2,204 newly served tracts, those served by Lev345 TCs had higher mean % poverty compared with those served by Lev12 TCs (15.7% vs 13.2% poverty, p < 0.05).

Discussion
Overall, access to trauma care has been improving in the United States. However, the majority of new TCs opened in locations with pre-existing access to trauma care. Nationwide, Level 3, 4, and 5 TCs have been responsible for expanding access to underserved populations.

Level of Evidence
Epidemiological, Level III
Comparison and critical assessment of single-cell Hi-C protocols
Authors: Gridina M. , Taskina A. , Lagunov T. , Nurislamov A. , Kulikova T. , Krasikova A. , Fishman V 
Published: June 2022

AbstractAdvances in single-cell sequencing technologies make it possible to study the genome architecture in single cells. The rapid growth of the field has been fueled by the development of innovative single-cell Hi-C protocols. However, the protocols vary considerably in their efficiency, bias, scale and costs, and their relative advantages for different applications are unclear.Here, we compare the two most commonly used single-cell Hi-C protocols. We use long-read sequencing to analyze molecular products of the Hi-C assay and show that whole-genome amplification step results in increased number of artifacts, larger coverage biases, and increased amount of noise compared to PCR-based amplification. Our comparison provides guidance for researchers studying chromatin architecture in individual cells.
Evaluating the impact on clinical task efficiency of a natural language processing algorithm for searching medical documents: Prospective crossover study
Authors: Park Eunsoo H , Watson Hannah I , Mehendale Felicity V , O’Neil Alison Q 
Published: June 2022

AbstractBackgroundInformation retrieval (IR) from the free text within Electronic Health Records (EHRs) is time-consuming and complex. We hypothesise that Natural Language Processing (NLP)-enhanced search functionality for EHRs can make clinical workflows more efficient and reduce cognitive load for clinicians.ObjectiveTo evaluate the efficacy of three levels of search functionality (no search, string search, and NLP-enhanced search) in supporting IR for clinical users from the free text of EHR documents in a simulated clinical environment.MethodsA clinical environment was simulated by uploading three sets of patient notes into an EHR research software application and presenting these alongside three corresponding IR tasks. Tasks contained a mixture of multiple choice and free text questions.A prospective crossover study design was used, for which three groups of evaluators were recruited, comprised of doctors (n=19) and medical students (n=16). Evaluators performed the three tasks using each of the search functionalities in an order according to their randomly assigned group. The speed and accuracy of task completion was measured and analysed, and user perceptions of NLP-enhanced search were reviewed in a feedback survey.ResultsNLP-enhanced search facilitated significantly more accurate task completion than both string search (5.26%, p=0.01) and no search (7.44%, p=0.05). NLP-enhanced search and string search facilitated similar task speeds, both showing an increase in speed over no search function (15.9%/11.6%, p=0.05). 93% of evaluators agreed that NLP-enhanced search would make clinical workflows more efficient than string search, with qualitative feedback reporting that NLP-enhanced search reduced cognitive load.ConclusionsTo the best of our knowledge, this study is the largest evaluation to date of different search functionalities for supporting target clinical users in realistic clinical workflows, with a 3-way prospective crossover study design. NLP-enhanced search improved both accuracy and speed of clinical EHR IR tasks compared to browsing clinical notes without search. NLP-enhanced search improved accuracy and reduced the number of searches required for clinical EHR IR tasks compared to direct search term matching.
A multicenter, prospective, cross-sectional, genotype-phenotype and longitudinal natural history study of Andersen-Tawil syndrome
Authors: Rajakulendran Sanjeev , Tristani-Firouzi Martin , Sadjadi Reza , Cleland James , Tawil Rabi , Meola Giovanni , Sansone Valeria , Trivedi Jaya , Cannon Stephen C , Hanna Michael G , Griggs Robert C. 
Published: June 2022

ABSTRACTObjectiveA multi-center, prospective, cross-sectional natural history study to define the clinical phenotype of Andersen-Tawil syndrome, validate its current diagnostic criteria, explore genotype-phenotype correlations, and establish clinically relevant endpoints for use in therapeutic trials.MethodsParticipants were followed at yearly intervals for two years. Outcome measures included attack frequency and duration, neurophysiological exercise testing and interictal muscle strength. Cardiac endpoints were QTc interval, presence of U-waves, frequency of ventricular ectopy and arrhythmias. Participants completed the SF-36 and underwent KCNJ2 gene analysis.Results28 participants were enrolled. The age range was 17 to 82 years. 23 participants harbored mutations in KCNJ2, including a new mutation, Y68D. All exhibited at least one skeletal feature with 26/28 exhibiting two or more. Common physical abnormalities were a small mandible (89%), low set ears (82%) and micromelia of hands or feet (71%). 26 participants reported periodic paralysis. The frequency of attacks varied from 12/week to 1/year, and duration from 12 minutes to 21 days. Common triggers for attacks were prolonged rest (85%) and exercise/exertion (73%). 20/25 had an abnormal long exercise test. A prolonged QTc interval was identified in 36% participants, U waves in 39% and ambulatory ECGs demonstrated runs of ventricular tachycardia in 32% and more than 10 000 ventricular couples in 14% of participants.InterpretationThere is extensive heterogeneity in both the spectrum and severity of Andersen-Tawil syndrome. Overall, the symptoms result in a significant impairment in quality of life. The cardiac and neurophysiological data could serve as outcome measures in future treatment trials.
Pharmacogenomics of GLP-1 Receptor Agonists: A genome wide analysis of observational data and large randomized controlled trials
Authors: Dawed Adem Y , Mari Andrea , McDonald Timothy J , Li Lin , Wang Shuaicheng , Hong Mun-Gwan , Sharma Sapna , Robertson Neil R , Mahajan Anubha , Wang Xuan , Walker Mark , Gough Stephen , ‘t Hart Leen M , Zhou Kaixin , Forgie Ian , Ruetten Hartmut , Pavo Imre , Bhatnagar Pallav , Jones Angus G , Pearson Ewan R ,   DIRECT consortium
Published: June 2022

SummaryBackgroundIn the treatment of type 2 diabetes (T2D), GLP-1 Receptor Agonists (GLP-1RA) lower glucose levels and body weight, and have cardiovascular benefits. GLP-1RA efficacy and side effects vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1RA treatment.MethodsWe studied HbA1c reduction at 6 months after starting GLP-1RA in 4,571 subjects with T2D from four prospective observational cohorts and two randomized clinical trials. We evaluated variants in GLP-1R, then undertook a genome-wide association study (GWAS) and gene-based burden test.FindingsVariation in HbA1c reduction with GLP-1RA treatment was associated with rs6923761G>A (Gly168Ser) in the GLP-1R (0.9 mmol/mol lower reduction in HbA1c per Serine, p=6.0×10−05) and low frequency variants in ARRB1 (pskato=6.72×10−08), largely driven by rs140226575G>A (Thr370Met) (2.7mmol/mol greater HbA1c reduction per Methionine, p=5.2×10−06). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian populations who have a higher frequency of this variant (6-11%) than in White populations. A genetic risk score derived from these two genes identified around 5% of the population who had a ∼30% greater reduction in HbA1c than the ∼43% of the population with the worse response.InterpretationThis first genome wide pharmacogenomic study of GLP-1RA has provided novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants may benefit from earlier initiation of GLP-1RA.FundingInnovative Medicines Initiative, Wellcome Trust
Identifying patients presenting in pain to the adult emergency department: A binary classification task and description of prevalence
Authors: Hughes J.A. , Douglas C. , Jones L. , Brown N.J. , Nguyen A. , Jarugula R. , Lyrstedt A. , Hazelwood S. , Wu Y. , Saleh F. , Chu K. 
Published: June 2022

AbstractBackgroundAccurate, reliable and efficient measures of pain-related presentations are essential to evaluate and improve pain care in the ED. Estimates of pain prevalence on arrival to the emergency department (ED) vary depending on the methods used. Artificial intelligence (AI) approaches are likely to be the future for identifying patients in pain from electronic health records (EHR). However, we need a robust method to identify these patients before this can occur. This study aims to identify patients presenting in pain to the ED using binary classification and to describe the population, treatment and outcomes.MethodsThis study employs a cross-sectional design using retrospective data routinely collected in the EHR at a single ED. A random sample of 10 000 patients was selected for inclusion over three years. Triage nursing assessment underwent binary classification by three expert clinicians. The prevalence of pain on arrival is the primary outcome. Patients with pain were compared to those without pain on arrival regarding demographics, treatment and outcomes.ResultsThe prevalence of pain on arrival was 55.2% (95%CI 54.2% - 56.2%). Patients who presented in pain differed from those without pain in terms of age, country of birth, socioeconomic status, mode of arrival, urgency and discharge destination. The median time to first analgesic medication was 65min (IQR 38 – 114 min), and 45.6% (95% CI 44.3% - 46.9%) of patients arriving in pain received analgesic medication.ConclusionsThe prevalence of pain on arrival compares well with previously reported figures using similar methods. Differences in the cohort presenting in pain compared to the population may represent differences in the prevalence or be an extension of previous bias seen in the documentation of pain. This work has set a rigorous methodology for identifying patients presenting with pain from the EHR. It will form the basis for future applications of AI to identify patients presenting in pain to the ED.
Sputum alarmin levels delineate distinct T2 cytokine pathways and patient subgroups in asthma
Authors: Gautam Samir , Chu Jen-Hwa , Cohen Avi J. , Kaur Ravdeep , Wilson Gabriella , Liu Qing , Gomez Jose , Rajaveen Haseena , Yan Xiting , Cohn Lauren , Clark Brian J. , Chupp Geoffrey 
Published: June 2022

ABSTRACTRationaleAsthma is a chronic airway disease driven by multiple immunologic pathways that determine the clinical response to therapy. Current diagnostic methods are incapable of discriminating subtypes of asthma and guiding targeted treatment. We hypothesized that sputum cytokine profiles could help to identify immunologically-defined disease subtypes and individualize therapy in patients with severe asthma.ObjectivesDefine asthma subtypes associated with sputum alarmin and cytokine levels.MethodsCross-sectional analysis of clinical features and sputum from 200 asthmatic patients was performed. 10 cytokines belonging to alarmin, T2, and non-T2 pathways were measured. Pearson correlation was used to identify cytokine modules. Latent class analysis was used to cluster patients by cytokine expression.Measurements and Main ResultsThree modules of highly correlated cytokines were identified including a non-T2 module, the IL-1βmod (IL-1β, IL-6, GCSF), and two distinct T2 modules: TSLPmod (TSLP, IL-4, IL-5, IL-9) and IL-33mod (IL-33, IL-13, IL-21). The TSLPmod was associated with asthma severity, airway obstruction, eosinophilia, and elevated FeNO. Patient clustering revealed three subgroups; two different subgroups showed expression of T2 modules.ConclusionsAnalysis of sputum cytokines revealed three discrete signaling modules in patients with asthma. Unexpectedly, the inclusion of alarmins led to separation of canonical T2 cytokines into two unique modules; IL-5 grouped with TSLP, while IL-13 grouped with IL-33. In addition, patient clustering revealed two distinct endotypes associated with T2 immune signaling. These findings indicate a new layer of immunologic heterogeneity within the T2 paradigm, and suggest that sputum cytokine profiling may hold diagnostic utility for patients with asthma.
Progressivity of out-of-pocket costs under Australia’s universal health care system: a national linked data study
Authors: Law HD , Marasinghe D , Butler D , Welsh J , Lancsar E , Banks E , Biddle N , Korda R 
Published: June 2022

ABSTRACTBackgroundIn line with affordability and equity principles, Medicare—Australia’s universal health care program—has measures to contain out-of-pocket costs (OOPC), particularly for lower income households. This study examined the distribution of OOPC for Medicare-subsidised out-of-hospital services and prescription medicines in Australian households, according to their ability to pay.MethodsOOPC for out-of-hospital services and medicines in 2017-18 were estimated for each household, using 2016 Australian Census data linked to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefit Scheme (PBS) claims. We derived household disposable income by combining income information from the Census linked to income tax and social security data. We quantified OOPC as a proportion of equivalised household disposable income and calculated Kakwani progressivity indices (K).ResultsUsing data from 85% (n=6,830,365) of all Census private households, OOPC as a percentage of equivalised household disposable income decreased from 1.16% in the poorest decile to 0.63% in the richest decile for MBS services, and from 1.35% to 0.35% for PBS medicines. The regressive trend was less pronounced for MBS services (K = −0.06), with percentage OOPC relatively stable between the 2nd and 9th income deciles; while percentage OOPC decreased substantially with increasing income for PBS medicines (K = −0.24).ConclusionOOPC for out-of-hospital Medicare services were mildly regressive while those for prescription medicines were distinctly regressive. Actions to reduce inequity in OOPC, particularly for medicines should be considered.