bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Performance of Bayesian Vancomycin Monitoring in the Critically Ill*
Authors: Narayan Sujita W. , Thoma Yann , Drennan Philip G. , Yejin Kim Hannah , Alffenaar Jan-Willem , Van Hal Sebastiaan , Patanwala Asad E.
Published: April 2021

OBJECTIVES:

It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill.

DESIGN:

Retrospective cohort study.

SETTING:

Single-center ICU.

PATIENTS:

Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the sd of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (–1.7 to 1.8 mg/L), which was lower with a posteriori estimate (–0.7 to 1.8 mg/L). However, all three models showed low precision in terms of sd (4.7–8.8 mg/L) and root mean square error (4.8–8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7–3.2 mg/L for < 20 mg/L; –5.1 to –2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations.

CONCLUSIONS:

Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously.
Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury
Authors: Xin Yi , Martin Kevin , Morais Caio C. A. , Delvecchio Paolo , Gerard Sarah E. , Hamedani Hooman , Herrmann Jacob , Abate Nicholas , Lenart Austin , Humayun Shiraz , Sidhu Uday , Petrov Mihail , Reutlinger Kristan , Mandelbaum Tal , Duncan Ian , Tustison Nicholas , Kadlecek Stephen , Chatterjee Shampa , Gee James C. , Rizi Rahim R. , Berra Lorenzo , Cereda Maurizio
Published: April 2021

OBJECTIVES:

It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury.

DESIGN:

Prospective, longitudinal imaging study.

SETTING:

Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA).

SUBJECTS:

Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome).

INTERVENTIONS:

Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics.

MEASUREMENTS AND MAIN RESULTS:

Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects.

CONCLUSIONS:

The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.
Next-generation sequencing for the management of sarcomas with no known driver mutations
Authors: Vyse Simon , Thway Khin , Huang Paul H. , Jones Robin L.
Published: April 2021

Purpose of review

Next-generation sequencing (NGS) has enabled fast, high-throughput nucleotide sequencing and has begun to be implemented into clinical practice for genomic-guided precision medicine in various cancer types. This review will discuss recent evidence that highlights opportunities for NGS to improve outcomes in sarcomas that have complex genomic profiles with no known driver mutations.

Recent findings

Global genomic signatures detectable by NGS including tumour mutational burden and microsatellite instability have potential as biomarkers for response to immunotherapy in certain sarcoma subtypes including angiosarcomas. Identification of hallmarks associated with ‘BRCAness’ and homologous recombination repair defects in leiomyosarcomas and osteosarcomas may predict sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. Lastly, the use of NGS for evaluating cancer predisposition in sarcomas may be useful for early detection, screening and surveillance.

Currently, the implementation of NGS for every sarcoma patient is not practical or useful. However, adopting NGS as a complementary approach in sarcomas with complex genomics and those with limited treatment options has the potential to deliver precision medicine to a subgroup of patients, with novel therapies such as immune checkpoint and PARP inhibitors. Moving forward, molecular tumour boards incorporating multidisciplinary teams of pathologists, oncologists and genomic specialists to interpret NGS data will complement existing tools in diagnosis and treatment decision making in sarcoma patients.
Virtual Synchronous Motivational Interviewing Training for Geographically Dispersed Interprofessional Learners
Authors: Bryan Jennifer L. , Saxon LaDonna C. , Mesidor Marie M. , Asghar-Ali Ali A.
Published: April 2021

Introduction:

Behavioral health and other preventable factors account for nearly half of all premature deaths in the United States. Motivational interviewing (MI) is effective for engaging ambivalent patients in behavior change. However, many clinicians report barriers to receiving MI training, including time, cost, and travel. This study examined the effect of a 2-day virtual MI training built around didactic and real-play learning activities.

Methods:

Thirty interprofessional clinicians from eight Veterans Affairs medical centers and their community-based outpatient clinics across 4 US states attended a 2-day virtual MI training. Participants completed a posttraining evaluation and a 3-month posttraining evaluation.

Results:

Participants reported that they learned new knowledge and skills, and they would be able to apply these to their practice (M > 4).They reported high satisfaction with the training and platform and found the technology easy to use (M > 4). In the 3-month posttraining survey, participants reported that they were using MI in their practice (M = 4.19) and that they would like additional support, such as additional reading (n = 8).

Discussion:

This study demonstrates the effect of a 2-day virtual MI training built around didactic and real-play learning activities. Virtual training particularly enhances training opportunities in rural settings. Our training removed travel and payment as barriers to participation.
A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas
Authors: Sanchez Jackee N. , Subramanian Chitra , Chanda Monica , Shanguan Gary , Zhang Nina , Wang Ton , Timmermann Barbara N. , Blagg Brian S.J. , Cohen Mark S.
Published: April 2021

Melanoma remains the most aggressive and fatal form of skin cancer, despite several FDA-approved targeted chemotherapies and immunotherapies for use in advanced disease. Of the 100 350 new patients diagnosed with melanoma in 2020 in the US, more than half will develop metastatic disease leading to a 5-year survival rate <30%, with a majority of these developing drug-resistance within the first year of treatment. These statistics underscore the critical need in the field to develop more durable therapeutics as well as those that can overcome chemotherapy-induced drug resistance from currently approved agents. Fortunately, several of the drug-resistance pathways in melanoma, including the proteins in those pathways, rely in part on Hsp90 chaperone function. This presents a unique and novel opportunity to simultaneously target multiple proteins and drug-resistant pathways in this disease via molecular chaperone inhibition. Taken together, we hypothesize that our novel C-terminal Hsp90 inhibitor, KU758, in combination with the current standard of care targeted therapies (e.g. vemurafenib and cobimetinib) can both synergize melanoma treatment efficacy in BRAF-mutant tumors, as well as target and overcome several major resistance pathways in this disease. Using in vitro proliferation and protein-based Western Blot analyses, our novel inhibitor, KU758, potently inhibited melanoma cell proliferation (without induction of the heat shock response) in vitro and synergized with both BRAF and MEK inhibitors in inhibition of cell migration and protein expression from resistance pathways. Overall, our work provides early support for further translation of C-terminal Hsp90 inhibitor and mitogen-activated protein kinase pathway inhibitor combinations as a novel therapeutic strategy for BRAF-mutant melanomas.
A Meta-analysis of Clinical Trials Evaluating the Impact of Bivalirudin-based Anticoagulation for Primary Percutaneous Coronary on Long-Term Mortality
Authors: Jagadish Pooja S. , Le Francis K. , Labroo Ajay , Nasr Abrar , Rashid Abdul , Khan Babar , Shah Rahman
Published: April 2021

Bivalirudin and heparin are the principal anticoagulants used during primary percutaneous coronary intervention (PCI) for patients experiencing ST-elevation myocardial infarctions. Based on previous meta-analyses, bivalirudin improves 30-day mortality rates compared with heparin, especially when vascular access is predominantly femoral. However, no meta-analysis has yet reported whether this mortality benefit with bivalirudin persists beyond 30 days. Scientific databases and websites were searched to find randomized controlled trials, and risk ratios (RRs) were calculated using random effect models. Data from 4 trials were analyzed. Compared with heparin ± glycoprotein IIb/IIIa inhibitors, bivalirudin decreased all-cause mortality [RR, 0.81; 95% confidence interval (CI), 0.69–0.94; P = 0.008], cardiac mortality (RR, 0.72; 95% CI, 0.60–0.88; P = 0.001), and net adverse clinical events (RR, 0.83; 95% CI, 0.72–0.97; P = 0.016) at 1 year. In conclusion, a bivalirudin-based anticoagulation strategy during primary percutaneous coronary intervention significantly decreases the 1-year risks for all-cause mortality, cardiac mortality, and net adverse clinical events compared with heparin ± glycoprotein IIb/IIIa inhibitor.
Obstetric and Gynecologic Genitourinary Fistulas
Authors: ABRAMS MEGAN , POPE RACHEL
Published: April 2021

Urinary incontinence shortly after childbirth or gynecologic surgery can be the result of obstetric or iatrogenic fistula formation. This can be a confusing and challenging diagnosis for medical providers. While the number of iatrogenic fistula cases is rising worldwide, obstetric fistulas are an issue uniquely particular to resource poor settings. Appropriate treatment of genitourinary fistulas spans beyond surgical intervention of leakage, and includes re-integration into the community, widespread education and counseling, and battling social stigma and cultural biases. Current and future research must focus on rigorous, unified efforts to set evidence-based practices to help the millions of women affected.
Thrombocytopenia and clear corneal incision cataract surgery
Authors: Reilly Grace R. , Tipton Caroline W. , Armbrust Karen R. , Boyd Kelly , Murray Jared J. , Kopplin Laura J. , Berkenstock Meghan K.
Published: April 2021

Purpose:

To investigate complications and outcomes of clear corneal incision cataract surgery in patients with thrombocytopenia.

Setting:

1 veterans hospital and 2 academic medical centers.

Design:

Multicenter retrospective chart review.

Methods:

All eyes of thrombocytopenic patients that underwent clear corneal incision cataract surgery with a platelet count of 100 × 103/μL or less measured within 30 days prior to surgery were included. Subject demographics, intraoperative complications, use of pupillary expansion devices, use of local anesthetic injections, and change in corrected distance visual acuity were recorded.

Results:

3 sites recorded 40 113 clear corneal incision cataract surgeries, of which 196 eyes (0.49%) of 150 thrombocytopenic patients were recorded. The mean platelet count in the study subjects was 73.0 ± 20.5 × 103/μL. Two cases of intraoperative iris hemorrhage that were readily and controlled occurred in conjunction with pupillary expansion. There were no bleeding complications associated with retrobulbar, peribulbar, or sub-Tenon anesthetic injections. There was a statistically significant improvement (P < .0001) in visual acuity post-operatively.

Conclusions:

Clear corneal incision cataract surgery with pupillary expansion devices and local anesthetic injections can be safely performed in patients with thrombocytopenia.
Frequency of Workplace Controls and Associations With Safety Perceptions Among a National Sample of US Food Retail Workers During the COVID-19 Pandemic
Authors: Ceryes Caitlin , Robinson Joelle , Biehl Erin , Wirtz Andrea L. , Barnett Daniel J. , Neff Roni
Published: April 2021

Objectives:

Explore workplace control frequencies and factors associated with US food retail workers’ safety perceptions during COVID-19.

Methods:

An online, cross-sectional survey captured working conditions and safety perceptions among a large, national sample of US food retail workers from July to October 2020.

Results:

Overall, 40.3% reported feeling “not so” or “not protected” by COVID-19 controls. Administrative controls were more commonly reported (56.8% reported ≥5 controls) than engineering (19.5% reported ≥3). Fomite-related controls were more common than those reducing interpersonal contact. After adjustment, organizational safety climate (prevalence ratio (PR): 1.53, 95% CI: 1.24, 1.89), and perceived strict prevention measure enforcement (PR: 0.60, 95% CI: 0.46, 0.78) were associated with safety perceptions.

Conclusions:

Many workers do not feel well-protected by COVID-19 controls. Safety climate and control enforcement are associated with workers’ COVID-19 safety perceptions.
Determining the Costs of Low-Back Pain Associated Sick Leave in the Dutch Workforce in the Period 2015 to 2017
Authors: van der Wurf Cas , Speklé Erwin , Schaafsma Frederieke , Coenen Pieter
Published: April 2021

Objective:

To investigate the costs of low-back pain associated sick leave of workers in the Netherlands from 2015 to 2017.

Methods:

We used longitudinal data form a large occupational health service regarding sick leave (registered by occupational physicians). Costs of sick leave due to low-back pain were estimated using the human capital approach, considering society and company perspectives.

Results:

A total of 7901 low-back pain episodes from 7161 unique workers were analyzed. We estimated an average episode of low-back pain sick leave was 129.42 days in duration and costed €16,191. The total extrapolated sick leave costs were estimated to be €244.7 million in 2017.

Conclusions:

Low-back pain remains to be a persistent problem in the working population, as it causes workers to take sick leave for considerable periods of time with considerable associated economic consequences.
How Should We Organize Care for Patients With Human Immunodeficiency Virus and Comorbidities? A Multisite Qualitative Study of Human Immunodeficiency Virus Care in the United States Department of Veterans Affairs
Authors: Bokhour Barbara G. , Bolton Rendelle E. , Asch Steven M. , Dvorin Kelly , Fix Gemmae M. , Gifford Allen L. , Hyde Justeen K. , McInnes D. Keith , Parker Victoria A. , Richardson Kelly , Skolnik Avy A. , Vaughan-Sarrazin Mary S. , Wu Juliet , Ohl Michael E.
Published: April 2021

Background:

With human immunodeficiency virus (HIV) now managed as a chronic disease, health care has had to change and expand to include management of other critical comorbidities. We sought to understand how variation in the organization, structure and processes of HIV and comorbidity care, based on patient-centered medical home (PCMH) principles, was related to care quality for Veterans with HIV.

Research Design:

Qualitative site visits were conducted at a purposive sample of 8 Department of Veterans Affairs Medical Centers, varying in care quality and outcomes for HIV and common comorbidities. Site visits entailed conduct of patient interviews (n=60); HIV care team interviews (n=60); direct observation of clinic processes and team interactions (n=22); and direct observations of patient-provider clinical encounters (n=45). Data were analyzed using a priori and emergent codes, construction of site syntheses and comparing sites with varying levels of quality.

Results:

Sites highest and lowest in both HIV and comorbidity care quality demonstrated clear differences in provision of PCMH-principled care. The highest site provided greater team-based, comprehensive, patient-centered, and data-driven care and engaged in continuous improvement. Sites with higher HIV care quality attended more to psychosocial needs. Sites that had consistent processes for comorbidity care, whether in HIV or primary care clinics, had higher quality of comorbidity care.

Conclusions:

Provision of high-quality HIV care and high-quality co-morbidity care require different care structures and processes. Provision of both requires a focus on providing care aligned with PCMH principles, integrating psychosocial needs into care, and establishing explicit consistent approaches to comorbidity management.
Deciphering transcriptional and functional heterogeneity in hematopoiesis with single-cell genomics
Authors: Martin-Rufino Jorge D. , Sankaran Vijay G.
Published: April 2021

Purpose of review

Single-cell genomic approaches have uncovered cell fate biases and heterogeneity within hematopoietic subpopulations. However, standard single-cell transcriptomics suffers from high sampling noise, which particularly skews the distribution of lowly expressed genes, such as transcription factors (TFs). This might preclude the identification of rare transcripts that define cell identity and demarcate cell fate biases. Moreover, these studies need to go hand in hand with relevant functional assays to ensure that observed gene expression changes represent biologically meaningful alterations.

Recent findings

Single-cell lineage tracing and functional validation studies have uncovered cell fate bias within transcriptionally distinct hematopoietic stem and progenitor subpopulations. Novel markers identified using these strategies have been proposed to prospectively isolate functionally distinct subpopulations, including long-term hematopoietic stem cells for ex vivo applications. Furthermore, the continuous nature of hematopoiesis has prompted the study of the relationship between stochastic transcriptional noise in hematopoietic TFs and cell fate determination.

An understanding of the limitations of single-cell genomic approaches and follow-up functional assays is critical to discern the technical and biological contribution of noise in hematopoietic heterogeneity, to identify rare gene expression states, and to uncover functionally distinct subpopulations within hematopoiesis.

Supplementary video

http://links.lww.com/COH/A23
Evaluation of Pediatric Hematology Referrals at a Tertiary University Hospital in West Texas
Authors: Bluhm Peyton , Eldem Irem , Abraham Angela , Almekdash Mhd Hasan , O’Suoji Chibuzo
Published: April 2021

One in 40 pediatric office visits in the United States result in referral to subspecialty care, mostly for secondary opinion. The aim of this study was to evaluate the necessity of pediatric hematology referrals from Eastern New Mexico and West Texas to a tertiary university hospital. Retrospective data was obtained from chart review based on referrals made to the Southwest Cancer Center in Lubbock, TX for abnormal complete blood count or coagulation tests. Necessity of referrals were assessed according to patient laboratory values before referral, at initial visit, and whether therapy was started by the primary care physician (PCP). One hundred one patients met the study criteria during the period in review. The most common reasons of referral were iron deficiency anemia, leukopenia or leukocytosis and other types of anemia. About 33% of the referrals were determined to be manageable by a PCP as either the correct therapy had been already started before referral and/or the laboratory values were back to normal at the time of the first subspecialty visit. The total estimated cost of unnecessary referrals, including clinic visits and laboratories were $82,888 excluding mileage costs, days of work-school missed, and child care. Incorporation of referral guidelines, improving communication between PCP and subspecialties, and utilizing age-sex appropriate values in the interpretation of results could prevent excessive subspecialty referrals.
Clinical Significance of MicroRNA-29a and MicroRNA-100 Gene Expression in Pediatric Acute Myeloid Leukemia
Authors: Said Fadwa , Tantawy Marwa , Sayed Ahmed , Ahmed Sonia
Published: April 2021

Aim:

The aim of this study was to evaluate the diagnostic and prognostic performance of miRNA-29a and miRNA-100 in pediatric acute myeloid leukemia (AML).

Patients and Methods:

In all, 73 children with diagnosed pediatric AML (based on standard morphologic, cytochemical, cytogenetic, immunologic, and molecular workup, and the French-American British classification) admitted to Children’s Cancer Hospital Egypt (CCHE-57357), and 9 healthy age-matched and sex-matched controls were recruited for a case-control study. Gene expression levels of miRNA-29a and miRNA-100 were assessed using real-time quantitative RT-PCR.

Results:

When diagnosed, patients had a significantly higher expression of miRNA-100 as against controls (median [range]: 12.99 [0.92-851.38] vs. 0.26 [0.03-2.67], P<0.001), with a significantly lower expression of miRNA-29a (2.08 [0.02-19.72] vs. 24.95 [15.48-42.54], P<0.001). Likewise, high-risk patients according to cytogenetic stratification had significantly higher miRNA-100 expression and lower miRNA-29a expression. Both miRNA-100 and miRNA-29a performed well as diagnostic markers of pediatric AML with an area under the curve of 0.977 (95% confidence interval [95% CI: 0.943-1.0]) and 0.994 (0.982-1.0) for miRNA-100 and miRNA-29a, respectively. Both miRNA-29a (odds ratio [95% CI]: 0.160 [0.054-0.474], P=0.001) and miRNA-100 (odds ratio [95% CI]: 1.997 [1.994-2.001], P=0.047) were identified as significant predictors of treatment response.

Conclusion:

The miRNA-29a and miRNA-100 expression may serve as diagnostic and prognostic markers in pediatric AML.
Pulmonary Actinomycosis and Mucormycosis Coinfection in a Patient With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia Undergoing Chemotherapy
Authors: Fujisaki Toru , Inagaki Jiro , Kouroki Masahiko , Honda Yuko , Matsuishi Toshiya , Kamizono Junji , Yasui Masahiro
Published: April 2021

Mucormycosis is an opportunistic and progressive infection, while actinomycosis usually grows gradually and rarely develops in immunocompromised patients. Here we report a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia who developed a pulmonary actinomycosis and mucormycosis coinfection. Once the diagnosis of actinomycosis was confirmed by bronchoscopy, lobectomy performed before stem cell transplantation revealed mucormycosis. The patient successfully underwent transplantation using a therapeutic antifungal agent for mucormycosis. When an immunocompromised patient develops an infection of unknown etiology, physicians should consider these pathogens as the possible cause. In addition, surgical intervention should be considered as an important treatment option.
Predictors of nasogastric tube removal in patients with stroke and dysphagia
Authors: Lee Kun-Chang , Liu Chien-Ting , Tzeng I-Shiang , Chie Wei-Chu
Published: April 2021

Dysphagia is present in 25–50% of patients with stroke. Therefore, studying the probability of nasogastric tube removal in such patients before discharge from the rehabilitation ward is crucial. In this study, we developed a model to predict the outcome of dysphagia in patients with stroke. A retrospective study was performed from May 2015 to December 2018. We reviewed the medical charts of all patients with a diagnosis of stroke receiving nasogastric tube feeding. Patients were divided into weaned and nonweaned groups to compare baseline characteristics and functional status. The weaned and nonweaned groups comprised 55 and 65 patients, respectively. In the final logistic regression analysis model, the Barthel index at admission, lip closing status, ability to answer simple questions and functional independence before stroke were used to develop a predictive model (Logit = 0.8942 × functional independence before this stroke + 1.1279 × ability to answer simple question + 0.5345 × lip-close status + 0.0546 × Barthel index at admission − 2.2805). The optimal cutoff point based on Youden’s index was more than −0.8403 with a sensitivity and specificity of 85.45 and 73.85%, respectively. The positive predicted value was 73.44%. In patients with stroke and dysphagia, a high Barthel index, intact lip closing status, ability to answer simple questions and better functional status before stroke appeared to affect nasogastric tube removal before discharge from the rehabilitation ward. Based on the final regression model, the proposed equation will help physicians and speech pathologists in planning patient care.
Implications of weight gain with newer anti-retrovirals: 10-year predictions of cardiovascular disease and diabetes
Authors: McCann Kaitlyn , Shah Shahini , Hindley Laura , Hill Andrew , Qavi Ambar , Simmons Bryony , Serenata Celicia , Sokhela Simiso , Venter Willem D.F.
Published: April 2021

Objective:

To evaluate the long-term risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) secondary to weight gain and clinical obesity associated with the initiation of integrase strand transfer inhibitors and tenofovir alafenamide (TAF) in the ADVANCE trial using validated risk equation tools.

Design:

Retrospective data analysis.

Methods:

In ADVANCE, 1053 treatment-naive participants in South Africa (99% black, 59% female) were randomized to 96 weeks of TAF/emtricitabine + dolutegravir (TAF/FTC + DTG), tenofovir disoproxil fumarate/FTC + DTG (TDF/FTC + DTG), or TDF/FTC + efavirenz (TDF/FTC/EFV). The 5 and 10-year risks of CVD were calculated using D:A:D, QRISK and Framingham, and T2DM risk using QDiabetes, Cambridge Diabetes and Leicester Practice Risk scores. Participants were included in this analysis if they were above 30 years old at baseline.

Results:

A total of 217 (TAF/FTC + DTG), 218 (TDF/FTC + DTG), and 215 (TDF/FTC/EFV) participants had 96-week data available. Weight gain was +8.1, +4.2, and +2.4 kg on TAF/FTC + DTG, TDF/FTC + DTG, and TDF/FTC/EFV, respectively. Participants on TAF/FTC + DTG had greatest risk scores for CVD (using QRISK) and T2DM, driven by weight changes. Differences were statistically significant between TAF/FTC + DTG and TDF/FTC/EFV for CVD risk using the QRISK equation, equivalent to one extra case per 1000 people treated over 10 years, and between all treatment groups for T2DM risk. Six extra T2DM cases were predicted on TAF/FTC + DTG vs. TDF/FTC + DTG using QDiabetes.

Conclusion:

Obesity, especially with TAF/FTC + DTG, drove increased risk of T2DM, with some evidence of greater CVD risk. However, predictive tools have not been validated in the HIV-positive and black African population.
Reconstruction of Soft Tissue Defects on the Face, Neck, and Chest by Expanded Cervico-Acromial Flap
Authors: Chen Sen , Li Yangqun , Ma Ning , Wang Weixin , Xu Lisi , Yang Zhe
Published: April 2021

Background:

Repairing the defects of face and neck remains a big challenge for plastic surgeons. Here we present a case series of pre-expanded cervico-acromial flaps in the repair of soft tissue defects.

Method:

This is a retrospective study that a total of 126 patients between 2001 and 2019 were included. One patient was excluded since he did not complete the treatment. All patients were followed for at least 0.5 years (range: 0.5–4 years, mean 2.50 years) after surgery.

Results:

All patients are satisfied with the appearance. The color and texture of expanded flaps were similar to surroundings. One patient (0.8%) had complete necrosis and received skin grafts. The size of cervico-acromial was 26-10 × 14-6 cm (mean, 15.389 ± 2.701× 8.341 ± 1.075 cm). The time of operation during stage 1 was 59.254 ± 9.895 minutes, 96.912 ± 18.936 minutes during stage 2, and 38.146 ± 9.478 minutes during stage 3. Surgical complication rate was 14.3%, given that 18 patients had complications following the surgery.

Conclusions:

The cercico-acromial flap is a reliable and multifunctional method for face, neck, and chest reconstruction.
Antemortem Heparin in Organ Donation After Circulatory Death Determination: A Systematic Review of the Literature
Authors: Honarmand Kimia , Alshamsi Fayez , Foroutan Farid , Rochwerg Bram , Belley-Cote Emilie , Mclure Graham , D’Aragon Frederick , Ball Ian M. , Sener Alp , Selzner Markus , Guyatt Gordon , Meade Maureen O.
Published: April 2021

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%–100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.
Atypical antipsychotics in the treatment of psychotic symptoms in Alzheimer’s disease: a systematic review
Authors: Vinaşi Ramona , Buciuta Andrei , Coman Horia George
Published: April 2021

With the advancement of Alzheimer’s disease as well as other types of dementia, in addition to the cognitive decline, psychiatric symptoms have been outlined, including psychotic symptoms. The aim of the study is to review the available results on the antipsychotic treatment of Alzheimer’s disease associated psychotic symptoms. The main objective of the study is to evaluate the efficacy of the treatment. The second objective is to assess the tolerability of this treatment. Double-blind, randomized, placebo-controlled trials, which took place over the course of at least 4 weeks, have been searched. Studies that compared one atypical antipsychotic to placebo, as well as more atypical antipsychotics, compared one to another, have been taken into account. In total 17 studies have been selected. The efficacy of the atypical antipsychotics has proven to be significant in most studies. Moreover, antipsychotic medication, such as risperidone, aripiprazole, olanzapine, quetiapine and pimavanserin, has been well tolerated. Atypical antipsychotics are the treatment of choice for psychotic symptoms in dementia. Despite the consistent results present in the literature up to this point, various antipsychotics remain insufficiently studied and would need more generous sample sizes for their outcomes to be substantiated.
Systematic review automation tool use by systematic reviewers, health technology assessors and clinical guideline developers: tools used, abandoned, and desired
Authors: Scott Anna Mae , Forbes Connor , Clark Justin , Carter Matt , Glasziou Paul , Munn Zachary
Published: April 2021

Objective

We investigated the use of systematic review automation tools by systematic reviewers, health technology assessors and clinical guideline developers.

Study design and settings

An online, 16-question survey was distributed across several evidence synthesis, health technology assessment and guideline development organisations internationally. We asked the respondents what tools they use and abandon, how often and when they use the tools, their perceived time savings and accuracy, and desired new tools. Descriptive statistics were used to report the results.

Results

253 respondents completed the survey; 89% have used systematic review automation tools – most frequently whilst screening (79%). Respondents’ ‘top 3’ tools include: Covidence (45%), RevMan (35%), Rayyan and GRADEPro (both 22%); most commonly abandoned were Rayyan (19%), Covidence (15%), DistillerSR (14%) and RevMan (13%). Majority thought tools saved time (80%) and increased accuracy (54%). Respondents taught themselves to how to use the tools (72%), and were most often prevented by lack of knowledge from their adoption (51%). Most new tool development was suggested for the searching and data extraction stages.

Conclusion

Automation tools are likely to take on an increasingly important role in high quality and timely reviews. Further work is required in training and dissemination of automation tools and ensuring they meet the desirable features of those conducting systematic reviews.
Real world evidence of calcifediol use and mortality rate of COVID-19 hospitalized in a large cohort of 16,401 Andalusian patients
Authors: Loucera Carlos , Peña-Chilet María , Esteban-Medina Marina , Muñoyerro-Muñiz Dolores , Villegas Román , Lopez-Miranda Jose , Rodriguez-Baño Jesus , Túnez Isaac , Bouillon Roger , Dopazo Joaquin , Gomez Jose Manuel Quesada
Published: April 2021

Background

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19.

Methods

We present a retrospective survival study that includes all Andalusian patients hospitalized between January and November 2020 because of COVID-19 infection. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of treatment with vitamin D metabolites for other indication previous to the hospitalization was studied with respect to patient survival by means of Kaplan-Meyer survival curves and Log Hazard Ratios, using a propensity score to compensate the disbalance of compared classes and the confounding factors. The availability of detailed patient data in the BPS allowed to obtain Real-World Evidence (RWE) of the effects of prior use of vitamin D or its metabolites on the mortality due to COVID-19 infection.

Findings

A retrospective cohort of 16.401patients was extracted from the BPS, which includes all the patients hospitalized with COVID-19 diagnosis between January and November 2020 in Andalusia, one of the largest regions in Europe with the size of an average median country. A total of 358 patients were found with cholecalciferol, and 193 with calcifediol, prescriptions 15 days before hospitalization. For a period extended to 30 days before hospitalization, the numbers increase to 416 and 210 and, respectively. Kaplan-Meyer survival curves and hazard ratios support an association between consumption of these metabolites and patient survival. Such association was stronger in calcifediol (Log Hazard Ratio, LHR = -1.27±0.32) than in cholecalciferol (LHR= -0.56±0.15), when prescribed 15 days before hospitalization This effect decreases when a larger 30 days period is considered (calcifediol LHR= -1.01±0.27 and cholecalciferol LHR= -0.27±0.12), suggesting that the closer was the treatment to the hospitalization the stronger the association.

Conclusions

A significant reduction in mortality in patients hospitalized with COVID-19 is associated with the prescription of vitamin D, especially calcifediol, within 15-30 days prior to hospitalization.
From first to second wave: follow-up of the prospective Covid-19 cohort (KoCo19) in Munich (Germany)
Authors: Radon Katja , Bakuli Abhishek , Pütz Peter , Gleut Ronan Le , Guggenbuehl Noller Jessica Michelle , Olbrich Laura , Saathoff Elmar , Garí Mercè , Schälte Yannik , Frahnow Turid , Wölfel Roman , Pritsch Michael , Rothe Camilla , Pletschette Michel , Rubio-Acero Raquel , Beyerl Jessica , Metaxa Dafni , Forster Felix , Thiel Verena , Castelletti Noemi , Rieß Friedrich , Diefenbach Maximilian N. , Fröschl Günter , Bruger Jan , Winter Simon , Frese Jonathan , Puchinger Kerstin , Brand Isabel , Kroidl Inge , Wieser Andreas , Hoelscher Michael , Hasenauer Jan , Fuchs Christiane
Published: April 2021

Background

In the 2ndyear of the Covid-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021.

Methods

The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4,433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys®Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N=2768) as well as leisure time activities (N=1263) were collected in summer 2020.

Results

Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2021 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences.

Conclusion

The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2ndwave of the pandemic. Antibodies remained present in the majority of baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.
Mapping the plague through natural language processing
Authors: Krauer Fabienne , Schmid Boris V.
Published: April 2021

Pandemic diseases such as plague have produced a vast amount of literature providing information about the spatiotemporal extent of past epidemics, circumstances of transmission, symptoms, or countermeasures. However, the manual extraction of such information from running text is a tedious process, and much of this information has therefore remained locked into a narrative format. Natural Language processing (NLP) is a promising tool for the automated extraction of epidemiological data from texts, and can facilitate the establishment of datasets. In this paper, we explore the utility of NLP to assist in the creation of a plague outbreak dataset. We first produced a gold standard list of toponyms by manual annotation of a German plague treatise published by Sticker in 1908. We then investigated the performance of five pre-trained NLP libraries (Google NLP, Stanford CoreNLP, spaCy, germaNER and Geoparser.io) for the automated extraction of location data from a compared to the gold standard. Of all tested algorithms, spaCy performed best (sensitivity 0.92, F1 score 0.83), followed closely by Stanford CoreNLP (sensitivity 0.81, F1 score 0.87). Google NLP had a slightly lower performance (F1 score 0.72, sensitivity 0.78). Geoparser and germaNER had a poor sensitivity (0.41 and 0.61) From the gold standard list we produced a plague dataset by linking dates and outbreak places with GIS coordinates. We then evaluated how well automated geocoding services such as Google geocoding, Geonames and Geoparser located these outbreaks correctly. All geocoding services performed poorly and returned the correct GIS information only in 60.4%, 52.7% and 33.8% of all cases. The rate of correct matches was particularly low when it came to historical regions and places. Finally, we compared our newly digitized plague dataset to a re-digitized version of the plague treatise by Biraben and provide an update of the spatio-temporal extent of the second pandemic plague outbreaks. We conclude that NLP tools have their limitations, but they are potentially useful to accelerate the collection of data and the generation of a global plague outbreak database.
COVID-19 Outcomes and Genomic characterization of SARS-CoV-2 isolated from Veterans in New England States
Authors: Lee Megan , Sallah Ya Haddy , Petrone Mary E. , Ringer Matthew , Cosentino Danielle , Vogels Chantal B.F. , Fauver Joseph R. , Alpert Tara , Grubaugh Nathan D. , Gupta Shaili
Published: April 2021

In an older cohort of veterans with a high comorbidity burden, age was the largest predictor of hospitalization, peak disease severity, and mortality. Most infections in six New England states until September, 2020, were from SARS-CoV-2 B.1 lineage, dominated by spike protein D614G substitution in 97.3% of samples.
Citrullination of glucokinase linked to autoimmune diabetes
Authors: Yang Mei-Ling , Horstman Sheryl , Gee Renelle , Guyer Perrin , Lam TuKiet T. , Kanyo Jean , Perdigoto Ana L. , Speake Cate , Greenbaum Carla J. , Overbergh Lut , Kibbey Richard G. , Herold Kevan C. , James Eddie A. , Mamula Mark J.
Published: April 2021

Inflammation, including reactive oxygen species and inflammatory cytokines in tissue microenvironments amplify the appearance of various post-translational modifications (PTMs) of self-proteins. Previously, a number of PTMs have been identified as autoimmune biomarkers in the initiation and progression of Type 1 diabetes (T1D). Herein, we have identified the citrullination of glucokinase (GK) as a result of inflammation, triggering autoimmunity and affecting its biological functions. Glucokinase is predominantly expressed in hepatocytes to regulate glycogen synthesis, and in pancreatic beta cells, where it acts as a glucose sensor to initiate glycolysis and insulin signaling. Herein, we demonstrate that glucokinase is citrullinated in inflamed non-obese diabetic (NOD) islets as well as in human GK. Autoantibodies against both native and citrullinated GK arise in both spontaneous human T1D and murine models. Likewise, autoreactive CD4+T cells to both native and citrullinated glucokinase epitopes are present in the circulation of T1D patients. Finally, citrullination alters GK biologic activity and suppresses glucose-stimulated insulin secretion. Our studies define glucokinase as a T1D biomarker, providing new insights into altering glucose metabolism, creating neoautoantigens, and better define the broad impact of PTMs on the tissue pathology of T1D.
AGENT: the Arabidopsis Gene Regulatory Network Tool for Exploring and Analyzing GRNs
Authors: Lau Vincent , Woo Rachel , Pereira Bruno , Pasha Asher , Esteban Eddi , Provart Nicholas J.
Published: April 2021

Gene regulatory networks (GRNs) are complex networks that capture multi-level regulatory events between one or more regulatory macromolecules, such as transcription factors (TFs), and their target genes. Advancements in screening technologies such as enhanced yeast-one-hybrid screens have allowed for high throughput determination of GRNs. However, visualization of GRNs in Arabidopsis has been limited toad hocnetworks and are not interactive. Here, we describe the Arabidopsis GEne Network Tool (AGENT) that houses curated GRNs and provides tools to visualize and explore them. AGENT features include expression overlays, subnetwork motif scanning, and network analysis. We show how to use AGENT’s multiple built-in tools to identify key genes that are involved in flowering and seed development along with identifying temporal multi-TF control of a key transporter in nitrate signaling. AGENT can be accessed athttps://bar.utoronto.ca/AGENT.