Publications by authors named "Kim Nguyen"

278 Publications

Relationship between adverse drug reactions and unlicensed/off-label drug use in hospitalized children (EREMI): A study protocol.

Therapie 2021 Feb 4. Epub 2021 Feb 4.

Department of Pharmacotoxicology, Hospices civils de Lyon, 69003 Lyon, France; UMR 5558, CRNS, LBBE, EMET, Université Lyon, 69008 Lyon, France; Inserm CIC 1407, EPICIME-Clinical Investigation Center, 69003 Lyon, France.

Introduction: To date, few studies have shown a significant association between off-label drug use and adverse drug reactions (ADRs). The main aims of this study is to evaluate the relationship between adverse drug reactions and unlicensed or off-label drugs in hospitalized children and to provide more information on prescribing practice, the amplitude, consequences of unlicensed or off-label drug use in pediatric inpatients.

Methods: In this multicenter prospective study started from 2013, we use the French summaries of product characteristics in Theriaque (a prescription products guide) as a primary reference source for determining pediatric drug labeling. The detection of ADRs is carried out spontaneously by health professionals and actively by research groups using a trigger tool and patients' electronic health records. The causality between suspected ADRs and medication is evaluated using the Naranjo and the French methods of imputability independently by pharmacovigilance center. All suspected ADRs are submitted for a second evaluation by an independent pharmacovigilance experts.

Strength And Limitations Of This Study: For our best knowledge, EREMI is the first large multicenter prospective and objective study in France with an active ADRs monitoring and independent ADRs validation. This study identifies the risk factors that could be used to adjust preventive actions in children's care, guides future research in the field and increases the awareness of physicians in off-label drug use and in detecting and declaring ADRs. As data are obtained through extraction of information from hospital database and medical records, there is likely to be some under-reporting of items or missing data. In this study the field specialists detect all adverse events, experts in pharmacovigilance centers assess them and finally only the ADRs assessed by the independent committee are confirmed. Although we recruit a high number of patients, this observational study is subject to different confounders.
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http://dx.doi.org/10.1016/j.therap.2021.01.057DOI Listing
February 2021

Deep learning-enabled imaging flow cytometry for high-speed Cryptosporidium and Giardia detection.

Cytometry A 2021 Feb 6. Epub 2021 Feb 6.

Nanyang Environment and Water Research Institute, Nanyang Technological University, Singapore, Singapore.

Imaging flow cytometry has become a popular technology for bioparticle image analysis because of its capability of capturing thousands of images per second. Nevertheless, the vast number of images generated by imaging flow cytometry imposes great challenges for data analysis especially when the species have similar morphologies. In this work, we report a deep learning-enabled high-throughput system for predicting Cryptosporidium and Giardia in drinking water. This system combines imaging flow cytometry and an efficient artificial neural network called MCellNet, which achieves a classification accuracy >99.6%. The system can detect Cryptosporidium and Giardia with a sensitivity of 97.37% and a specificity of 99.95%. The high-speed analysis reaches 346 frames per second, outperforming the state-of-the-art deep learning algorithm MobileNetV2 in speed (251 frames per second) with a comparable classification accuracy. The reported system empowers rapid, accurate, and high throughput bioparticle detection in clinical diagnostics, environmental monitoring and other potential biosensing applications.
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http://dx.doi.org/10.1002/cyto.a.24321DOI Listing
February 2021

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

PLoS One 2021 5;16(2):e0246131. Epub 2021 Feb 5.

Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town and Durban, South Africa.

Background: Gamma-glutamyl transferase (GGT) has recently been reported as a biomarker for cardiovascular (CVD) risk in general populations. We investigated the associations of GGT with cardio-metabolic diseases and CVD risk in South Africans living with HIV.

Methods: In this cross-sectional study, HIV-infected adults were randomly recruited across 17 HIV clinics in the Western Cape Province. Homeostatic model assessment for insulin resistance (HOMA-IR), hypertension, diabetes, metabolic syndrome by Joint Interim Statement criteria (JIS-MS), a ≥5% and ≥10% predicted risk for a CVD event within 10 years by the Framingham risk score (10-years-CVD risk) were computed. Associations between GGT and cardio-metabolic trait were explored using linear and binomial logistic regressions adjusted for age, gender, lifestyle behaviours and HIV-related characteristics.

Results: Among 709 participants (561 women, mean age 38.6 years), log-GGT was positively associated with waist circumference (β=2.75; p<0.001), diastolic blood pressure (β=1.65; p=0.006), total cholesterol (β=0.21; p<0.001), low-density lipoprotein-cholesterol (β=0.16; p<0.001), high-density lipoprotein-cholesterol and log-triglycerides (both β=0.12; p<0.001), fasting plasma glucose (β=0.19; p=0.031), 2-hour-post-glucose-load plasma glucose (β=0.26; p=0.007), HOMA-IR (β=0.13; p=0.001), log-high-sensitivity C-reactive-protein (β=0.3; p<0.001) in linear regression analyses; with hypertension [OR=1.41 (95%CI, 1.13-1.75); p=0.001], JIS-MS [OR=1.33 (1.05-1.68); p=0.016], ≥5% 10-year-CVD risk [OR=1.55 (1.24-1.9400); p<0.001] and ≥10% 10-year-CVD risk [OR=1.56 (1.08-2.23); p=0.016] but not with diabetes [OR=1.24 (0.88-1.71), p=0.205] in logistic regression analyses.

Conclusions: In this study, GGT levels were associated with cardio-metabolic variables independent of HIV specific attributes. If confirmed in longitudinal studies, GGT evaluation maybe included in CVD risk monitoring strategies in people living with HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864415PMC
February 2021

A Magnetically Guided Self-Rolled Microrobot for Targeted Drug Delivery, Real-Time X-Ray Imaging, and Microrobot Retrieval.

Adv Healthc Mater 2021 Jan 27:e2001681. Epub 2021 Jan 27.

Korea Institute of Medical Microrobotics, 43-26, Cheomdangwagi-ro 208-beon-gil, Buk-gu, Gwangju, 61011, South Korea.

Targeted drug delivery using a microrobot is a promising technique capable of overcoming the limitations of conventional chemotherapy that relies on body circulation. However, most studies of microrobots used for drug delivery have only demonstrated simple mobility rather than precise targeting methods and prove the possibility of biodegradation of implanted microrobots after drug delivery. In this study, magnetically guided self-rolled microrobot that enables autonomous navigation-based targeted drug delivery, real-time X-ray imaging, and microrobot retrieval is proposed. The microrobot, composed of a self-rolled body that is printed using focused light and a surface with magnetic nanoparticles attached, demonstrates the loading of doxorubicin and an X-ray contrast agent for cancer therapy and X-ray imaging. The microrobot is precisely mobilized to the lesion site through automated targeting using magnetic field control of an electromagnetic actuation system under real-time X-ray imaging. The photothermal effect using near-infrared light reveals rapid drug release of the microrobot located at the lesion site. After drug delivery, the microrobot is recovered without potential toxicity by implantation or degradation using a magnetic-field-switchable coiled catheter. This microrobotic approach using automated control method of the therapeutic agents-loaded microrobot has potential use in precise localized drug delivery systems.
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http://dx.doi.org/10.1002/adhm.202001681DOI Listing
January 2021

Guide-wired Helical Microrobot for Percutaneous Revascularization in Chronic Total Occlusion in-vivo Validation.

IEEE Trans Biomed Eng 2020 Dec 22;PP. Epub 2020 Dec 22.

Objective: For the revascularization in small vessels such as coronary arteries, we present a guide-wired helical microrobot mimicking the corkscrew motion for mechanical atherectomy that enables autonomous therapeutics and minimizing the radiation exposure to clinicians.

Methods: The microrobot is fabricated with a spherical joint and a guidewire. A previously developed external electromagnetic manipulation system capable of high power and frequency is incorporated and an autonomous guidance motion control including driving and steering is implemented in the prototype. We tested the validity of our approach in animal experiments under clinical settings. For the in vivo test, artificial thrombus was fabricated and placed in a small vessel and atherectomy procedures were conducted.

Results: The devised approach enables us to navigate the helical robot to the target area and successfully unclog the thrombosis in rat models in vivo.

Conclusion: This technology overcomes several limitations associated with a small vessel environment and promises to advance medical microrobotics for real clinical applications while achieving intact operation and minimizing radiation exposures to clinicians.

Significance: Advanced microrobot based on multi-discipline technology could be validated in vivo for the first time and that may foster the microrobot application at clinical sites.
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http://dx.doi.org/10.1109/TBME.2020.3046513DOI Listing
December 2020

Change in Compliance of Staff at 4 Vietnam Universities after the Enactment of Smoke-free Environment Decree.

Environ Health Insights 2020 6;14:1178630220972957. Epub 2020 Dec 6.

University of Queensland, Saint Lucia, Australia.

Background: The Tobacco Control Law in Vietnam was adopted in 2012 and came into force from May 2013, followed by a number of guiding sub-law legal documents. Smoke-free campus policy in university is considered an important measure to protect people from secondhand smoking as well as staffs and students will be in favour of the policy. Furthermore, there has been evidence suggested that smoke-free policy had positive impact on active smoking as well as anti-smoking attitude.

Methods: A cross-sectional self-administered study of staff at 4 universities were conducted in 2 phases, Phase 1 as early introduction of the Law (n = 900) and Phase 2 as 1-year post (n = 885). Demographics, tobacco consumption, compliance status and compliance with awareness towards the campus smoking regulations were assessed in both phases.

Results: Daily smoking prevalence decreased significantly ( < .05) 1 year after implementing the smoke-free policy, while a significant increase in occasional smoking ( < .01). Compliance of staff to the regulation the campus should be indoor smoke-free was significantly increase at Phase 2 compared to Phase 1, however participants reported there would be places on campus that smokers frequently violated the smoke-free regulations.

Conclusions: The study indicated a significant positive change in compliance of staff at the 4 universities after the implementation of the Tobacco Control Law, included the smoke-free policy. Although the prevalence of tobacco smoking in this study was low, the proportion of respondents who reported to reduce infringement the smoke-free policy suggests support for staff smokers would be beneficial. Raising awareness and enforcement is likely to enhance the long-term outcomes of the implementation of smoke-free environment.
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http://dx.doi.org/10.1177/1178630220972957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724396PMC
December 2020

Machine Learning-Based Pipeline for High Accuracy Bioparticle Sizing.

Micromachines (Basel) 2020 Dec 7;11(12). Epub 2020 Dec 7.

School of Electrical & Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore.

High accuracy measurement of size is essential in physical and biomedical sciences. Various sizing techniques have been widely used in sorting colloidal materials, analyzing bioparticles and monitoring the qualities of food and atmosphere. Most imaging-free methods such as light scattering measure the averaged size of particles and have difficulties in determining non-spherical particles. Imaging acquisition using camera is capable of observing individual nanoparticles in real time, but the accuracy is compromised by the image defocusing and instrumental calibration. In this work, a machine learning-based pipeline is developed to facilitate a high accuracy imaging-based particle sizing. The pipeline consists of an image segmentation module for cell identification and a machine learning model for accurate pixel-to-size conversion. The results manifest a significantly improved accuracy, showing great potential for a wide range of applications in environmental sensing, biomedical diagnostical, and material characterization.
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http://dx.doi.org/10.3390/mi11121084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762436PMC
December 2020

Multifunctional Biodegradable Microrobot with Programmable Morphology for Biomedical Applications.

ACS Nano 2021 01 8;15(1):1059-1076. Epub 2020 Dec 8.

Korea Institute of Medical Microrobotics (KIMIRo), 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju, 61011, Korea.

We described a magnetic chitosan microscaffold tailored for applications requiring high biocompatibility, biodegradability, and monitoring by real-time imaging. Such magnetic microscaffolds exhibit adjustable pores and sizes depending on the target application and provide various functions such as magnetic actuation and enhanced cell adhesion using biomaterial-based magnetic particles. Subsequently, we fabricated the magnetic chitosan microscaffolds with optimized shape and pore properties to specific target diseases. As a versatile tool, the capability of the developed microscaffold was demonstrated through laboratory tasks and therapeutic applications for liver cancer therapy and knee cartilage regeneration. We anticipate that the optimal design and fabrication of the presented microscaffold will advance the technology of biopolymer-based microscaffolds and micro/nanorobots.
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http://dx.doi.org/10.1021/acsnano.0c07954DOI Listing
January 2021

Decentralised, small-scale coagulation-membrane treatment of wastewater from metal recycling villages - a case study from Vietnam.

Water Sci Technol 2020 Nov;82(10):2125-2133

Le Quy Don Technical University, Hanoi, Vietnam E-mail:

Effective treatment of wastewaters laden with heavy metals is critical to the sustainable social and economic growth of metal recycling villages in Vietnam. Currently, most wastewaters from metal recycling villages in Vietnam are directly discharged, posing great threats to the environment and human health. In this study, a small-scale combined coagulation-membrane filtration treatment of wastewater collected from a metal recycling village in Vietnam was experimentally investigated. The experimental results manifested the technical viability of the combined coagulation-membrane filtration process for the treatment of the heavily polluted metal recycling wastewater for beneficial reuse. In this combined treatment process, coagulation using ferric chloride (FeCl) served as a pre-treatment prior to the microfiltration (MF)/reverse osmosis (RO) process. Under the optimised conditions, coagulation at the dosage of 0.2 g FeCl per 1,000 ml wastewater removed more than 90% of heavy metals (i.e. most notably including aluminium and chromium) from the wastewater, reducing the aluminium and chromium concentrations in the wastewater from 548.0 to 52.3 mg/L to 32.6 and 1.7 mg/L, respectively. The MF treatment of the wastewater following the coagulation further removed suspended solids and organic matters, rendering the wastewater safe for the subsequent RO filtration with respect to membrane fouling. Given the efficient pre-treatment of coagulation and MF, the RO process at the controlled water recovery of 50% was able to effectively treat the wastewater to potable water.
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http://dx.doi.org/10.2166/wst.2020.493DOI Listing
November 2020

A Bump-Hole Strategy for Increased Stringency of Cell-Specific Metabolic Labeling of RNA.

ACS Chem Biol 2020 12 21;15(12):3099-3105. Epub 2020 Nov 21.

Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California 92697, United States.

Profiling RNA expression in a cell-specific manner continues to be a grand challenge in biochemical research. Bioorthogonal nucleosides can be utilized to track RNA expression; however, these methods currently have limitations due to background and incorporation of analogs into undesired cells. Herein, we design and demonstrate that uracil phosphoribosyltransferase can be engineered to match 5-vinyluracil for cell-specific metabolic labeling of RNA with exceptional specificity and stringency.
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http://dx.doi.org/10.1021/acschembio.0c00755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814973PMC
December 2020

FANCM c5791C>T stopgain mutation (rs144567652) is a familial colorectal cancer risk factor.

Mol Genet Genomic Med 2020 12 29;8(12):e1532. Epub 2020 Oct 29.

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Purpose: While familial aggregation of colorectal cancer (CRC) is recognized, the majority of the germline predisposition factors remain unidentified, and many high-risk CRC pedigrees remain unexplained by known risk variants. Fanconi Anemia genes have been recognized to be associated with cancer risk. Notably, FANCM (OMIM 609644) variants have been reported to confer risk for CRC and breast cancer.

Methods: Exome sequencing of CRC-affected cousins in a set of 47 independent extended high-risk CRC pedigrees identified a candidate set of rare, shared variants. Variants were tested for association with risk in 744 Utah CRC cases and 1525 controls, and for segregation with CRC in affected relatives.

Results: A FANCM stopgain variant was observed in two CRC-affected cousin pairs, each from an independent Utah high-risk pedigree, and yielded a nonsignificant, but elevated OR = 2.05 in a set of Utah cases and controls. Segregation of the variant to other related CRC-affected cases was observed in the two extended pedigrees.

Conclusion: A rare stopgain variant in FANCM (rs144567652) that is recognized as a breast cancer predisposition variant, and that has previously been proposed, but not confirmed, as a CRC predisposition variant, is validated here as a risk factor for familial CRC.
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http://dx.doi.org/10.1002/mgg3.1532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767553PMC
December 2020

Three new diphenyl ethers from the lichen (Nyl.) Hale (Parmeliaceae).

Nat Prod Res 2020 Oct 27:1-7. Epub 2020 Oct 27.

Faculty of Chemistry, Graduate University of Science and Technology, Academy of Science and Technology, Hanoi, Vietnam.

Three new diphenyl ethers, named praesorethers E, F and G (, and ), were isolated from the lichen . Their chemical structures were elucidated on the basis of extensively spectroscopic analysis including HR-ESI-MS and NMR as well as comparison with previously published data. These compounds were evaluated for the cytotoxicity against three human cancer cell lines (HeLa, NCI-H460 and MCF-7) using SRB assay. As results, and exhibited weak cytotoxic activity against three tested cancer cell lines with the inhibitive percentage of 64-79.9% at the concentration of 100 μg/mL while was inactive.
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http://dx.doi.org/10.1080/14786419.2020.1837818DOI Listing
October 2020

Human adipose-derived mesenchymal stem cell-based medical microrobot system for knee cartilage regeneration in vivo.

Sci Robot 2020 01;5(38)

Korea Institute of Medical Microrobotics (KIMIRo), 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Korea.

Targeted cell delivery by a magnetically actuated microrobot with a porous structure is a promising technique to enhance the low targeting efficiency of mesenchymal stem cell (MSC) in tissue regeneration. However, the relevant research performed to date is only in its proof-of-concept stage. To use the microrobot in a clinical stage, biocompatibility and biodegradation materials should be considered in the microrobot, and its efficacy needs to be verified using an in vivo model. In this study, we propose a human adipose-derived MSC-based medical microrobot system for knee cartilage regeneration and present an in vivo trial to verify the efficacy of the microrobot using the cartilage defect model. The microrobot system consists of a microrobot body capable of supporting MSCs, an electromagnetic actuation system for three-dimensional targeting of the microrobot, and a magnet for fixation of the microrobot to the damaged cartilage. Each component was designed and fabricated considering the accessibility of the patient and medical staff, as well as clinical safety. The efficacy of the microrobot system was then assessed in the cartilage defect model of rabbit knee with the aim to obtain clinical trial approval.
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http://dx.doi.org/10.1126/scirobotics.aay6626DOI Listing
January 2020

Heavy Metal Tolerance of Novel Yeast Isolated from Vietnamese Mangosteen.

Mycobiology 2020 Jun 2;48(4):296-303. Epub 2020 Jun 2.

Institute of Biotechnology, Hue University, Hue, Viet Nam.

Three yeast strains (Hue-1, Hue-8, and Hue-19) with strong heavy metal tolerance were isolated from mangosteen from Hue city, Vietnam. They exhibited identical phenotype and phylogeny. Sequence analysis of the D1/D2 region of the LSU rRNA gene and the internal transcribed spacer (ITS) region demonstrated that the closest relative of these strains is sp. with 2.12% and 3.55-3.7% divergence in the D1/D2 domain, and ITS domain, respectively. Based on the physiological, biochemical, and molecular data, the three strains belong to a novel species of genus, for which the name sp. nov. is proposed. These strains are highly tolerant of heavy metals compared to other yeasts, being able to grow in the presence of 2 mM Pb (II), 2 mM Cd (II), and up to 5 mM Ni (II), but no growth was observed in the presence of 1 mM As (III).
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http://dx.doi.org/10.1080/12298093.2020.1767020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476527PMC
June 2020

Telemedicine During COVID-19 and Beyond: A Practical Guide and Best Practices Multidisciplinary Approach for the Orthopedic and Neurologic Pain Physical Examination.

Pain Physician 2020 08;23(4S):S205-S238

LSU Health Science Center, New Orleans.

Background: The COVID pandemic has impacted almost every aspect of human interaction, causing global changes in financial, health care, and social environments for the foreseeable future. More than 1.3 million of the 4 million cases of COVID-19 confirmed globally as of May 2020 have been identified in the United States, testing the capacity and resilience of our hospitals and health care workers. The impacts of the ongoing pandemic, caused by a novel strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have far-reaching implications for the future of our health care system and how we deliver routine care to patients. The adoption of social distancing during this pandemic has demonstrated efficacy in controlling the spread of this virus and has been the only proven means of infection control thus far. Social distancing has prompted hospital closures and the reduction of all non-COVID clinical visits, causing widespread financial despair to many outpatient centers. However, the need to treat patients for non-COVID problems remains important despite this pandemic, as care must continue to be delivered to patients despite their ability or desire to report to outpatient centers for their general care. Our national health care system has realized this need and has incentivized providers to adopt distance-based care in the form of telemedicine and video medicine visits. Many institutions have since incorporated these into their practices without financial penalty because of Medicare's 1135 waiver, which currently reimburses telemedicine at the same rate as evaluation and management codes (E/M Codes). Although the financial burden has been alleviated by this policy, the practitioner remains accountable for providing proper assessment with this new modality of health care delivery. This is a challenge for most physicians, so our team of national experts has created a reference guide for musculoskeletal and neurologic examination selection to retrofit into the telemedicine experience.

Objectives: To describe and illustrate musculoskeletal and neurologic examination techniques that can be used effectively in telemedicine.

Study Design: Consensus-based multispecialty guidelines.

Setting: Tertiary care center.

Methods: Literature review of the neck, shoulder, elbow, wrist, hand, lumbar, hip, and knee physical examinations were performed. A multidisciplinary team comprised of physical medicine and rehabilitation, orthopedics, rheumatology, neurology, and anesthesia experts evaluated each examination and provided consensus opinion to select the examinations most appropriate for telemedicine evaluation. The team also provided consensus opinion on how to modify some examinations to incorporate into a nonhealth care office setting.

Results: Sixty-nine examinations were selected by the consensus team. Household objects were identified that modified standard and validated examinations, which could facilitate the examinations.The consensus review team did not believe that the modified tests altered the validity of the standardized tests.

Limitations: Examinations selected are not validated for telemedicine. Qualitative and quantitative analyses were not performed.

Conclusions: The physical examination is an essential component for sound clinical judgment and patient care planning. The physical examinations described in this manuscript provide a comprehensive framework for the musculoskeletal and neurologic examination, which has been vetted by a committee of national experts for incorporation into the telemedicine evaluation.
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August 2020

The Performance of the New 2019-EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus in Children and Young Adults.

Arthritis Care Res (Hoboken) 2020 Aug 25. Epub 2020 Aug 25.

Division of Rheumatology, Cincinnati Children's Hospital Medical Center Cincinnati, OH, United States.

Objective: To compare the diagnostic usefulness of the 2019 European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) to that of the 1997-ACR classification criteria for SLE (1997-ACR) when applied to youths (≤ 21 years) with SLE.

Methods: Data were extracted from electronic health records of patients followed at a large academic pediatric hospital. The treating rheumatologist's diagnosis of SLE served as the standard criterion for identifying SLE patients (cases). Controls were patients with juvenile dermatomyositis (JDM), juvenile scleroderma (jSc) or juvenile systemic sclerosis (jSSc). The 2019-EULAR/ACR criteria and the 1997-ACR criteria were tested against the standard criterion.

Results: A total of 112 SLE patients aged 2-21 years and 105 controls aged 1-19 years (66% JDM, 34% jSc or jSSc) were available for analysis. The 2019-EULAR/ACR criteria had significantly higher sensitivity (85% vs 72%; p=0.023) and similar specificity (83% vs 87%; p=0.456) than the 1997-ACR criteria. The mean±SD 2019-EULAR/ACR classification summary scores were significantly higher among non-White than White cases (22.41±10.04 vs. 17.59±9.19; p<0.01). The sensitivity of the 2019-EULAR/ACR criteria in non-White/White cases was 92%/80% (p=0.08) vs 83%/64% (p<0.02) for the 1997-ACR criteria. The sensitivity of the 2019-EULAR/ACR criteria was not affected by age or gender.

Conclusion: The 2019-EULAR/ACR criteria efficiently classify youths with SLE, irrespective of age, gender and race. Compared to the 1997-ACR criteria, the new criteria are significantly more sensitive and similarly specific in youths with SLE.
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http://dx.doi.org/10.1002/acr.24430DOI Listing
August 2020

Trends in hydrocodone combination product exposures reported to California Poison Control System (CPCS) following DEA rescheduling.

Clin Toxicol (Phila) 2020 Aug 25:1-7. Epub 2020 Aug 25.

Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.

Context: On October 6, 2014, the United States Drug Enforcement Administration (DEA) implemented a regulatory change for hydrocodone combination products (HCPs), moving them from Schedule III to II, in an effort to decrease drug overdoses. Existing research suggests this regulatory action reduced HCP prescribing and dispensing; however, there is limited research assessing its possible effects on overdoses and accidental exposures.

Objective: To analyze the changes in opioid exposures reported to the California Poison Control System (CPCS) before and after DEA rescheduling of HCPs.

Methods: We collected monthly exposure data reported to CPCS from 2012 to 2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Additional analyses were done to assess any changes in exposures resulting in severe outcomes (moderate or major health effects). For HCPs, we also conducted logistic regressions to identify characteristics of exposures resulting in severe outcomes before and after rescheduling.

Results: Overall monthly opioid exposures reported to CPCS decreased after DEA rescheduling of HCPs. These decreases were significant for HCP, tramadol, and morphine ( < 0.001). Exposures significantly increased for heroin and fentanyl ( < 0.001). There were no significant changes in the share of severe outcomes attributed to HCP exposures after rescheduling.

Discussion: The DEA rescheduling of HCPs was associated with a significant decrease in HCP exposures and prescription opioid exposures overall, but was associated with increased fentanyl and heroin exposures. While other initiatives may have contributed to this decrease, our findings suggest that rescheduling may be a useful regulatory strategy to reduce drug exposures.

Conclusion: DEA rescheduling of HCPs was associated with a significant reduction in prescription opioid exposures, suggesting that rescheduling high-risk drugs may be an effective strategy to improve public health.
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http://dx.doi.org/10.1080/15563650.2020.1803350DOI Listing
August 2020

Ambulatory Erector Spinae Plane Continuous Nerve Catheter for Acute Pain Management Following Rib Resection for Slipping Rib Syndrome in an Adolescent: A Case Report.

A A Pract 2020 Apr;14(6):e01210

From the *Department of Pediatric Anesthesiology †Division of Pediatric Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago Illinois.

Continuous regional analgesia techniques for ambulatory management of postoperative thoracic and abdominal wall pain are limited. We report the placement of an erector spinae plane (ESP) catheter in a pediatric patient who underwent rib resection for slipping rib syndrome and was discharged on postoperative day 1 with an elastomeric pump for continued regional analgesia in the ambulatory setting. The patient required minimal opioids while the catheter was in place and experienced a functional level that surpassed her preoperative state. Ambulatory ESP peripheral nerve catheters are a feasible and potentially effective option for the treatment of acute postsurgical pain in children.
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http://dx.doi.org/10.1213/XAA.0000000000001210DOI Listing
April 2020

Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study.

Hum Psychopharmacol 2020 11 1;35(6):1-7. Epub 2020 Aug 1.

Institute of Mental Health, Singapore, Singapore.

Objective: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

Methods: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.

Results: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

Conclusions: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.
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http://dx.doi.org/10.1002/hup.2752DOI Listing
November 2020

Ultrasound-guided maxillary nerve block via the pterygopalatine fossa: maxillary artery is the key.

Reg Anesth Pain Med 2020 Dec 9;45(12):1029-1030. Epub 2020 Jun 9.

Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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http://dx.doi.org/10.1136/rapm-2020-101705DOI Listing
December 2020

A new triterpenoid saponin from .

Nat Prod Res 2020 Jun 5:1-6. Epub 2020 Jun 5.

Department of Chemistry, HCMC University of Education, Ho Chi Minh City, Vietnam.

From the ethanol extract of , collected at Phu Yen province, Viet Nam, one new triterpenoid saponin () and four known compounds () were isolated. By means of NMR and HR-ESI-MS analyses, their structure was elucidated as 3--(β-D-xylopyranosyl-(1→3)-β-D-xylopyranosyl)spergulagenin A or glinusopposide V (), glinusopposide L (), spergulin B (), vitexin () and astralagin (). Two compounds () showed weak inhibitory activity against .
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http://dx.doi.org/10.1080/14786419.2020.1774756DOI Listing
June 2020

TBC1D24 regulates recycling of clathrin-independent cargo proteins mediated by tubular recycling endosomes.

Biochem Biophys Res Commun 2020 07 29;528(1):220-226. Epub 2020 May 29.

Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. Electronic address:

Many plasma membrane proteins enter cells by clathrin-independent endocytosis (CIE). Rab family small GTPases play pivotal roles in CIE and following intracellular trafficking of cargo proteins. Here, we provide evidence that TBC1D24, which contains an atypical Rab GAP domain, facilitates formation of tubular recycling endosomes (TREs) that are a hallmark of the CIE cargo trafficking pathway in HeLa cells. Overexpression of TBC1D24 in HeLa cells dramatically increased TREs loaded with CIE cargo proteins, while deletion of TBC1D24 impaired TRE formation and delayed the recycling of CIE cargo proteins back to the plasma membrane. We also found that TBC1D24 binds to Rab22A, through which TBC1D24 regulates TRE-mediated CIE cargo recycling. These findings provide insight into regulatory mechanisms for CIE cargo trafficking.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.007DOI Listing
July 2020

Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region.

Asia Pac Psychiatry 2020 Dec 29;12(4):e12393. Epub 2020 May 29.

Institute of Mental Health, Buangkok Green Medical Park, Singapore, Singapore.

Introduction: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.

Methods: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region.

Results: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications.

Discussion: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.
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http://dx.doi.org/10.1111/appy.12393DOI Listing
December 2020

Value of reflectance confocal microscopy for the monitoring of rosacea during treatment with topical ivermectin.

J Dermatolog Treat 2020 Mar 19:1-9. Epub 2020 Mar 19.

Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.

: Reflectance confocal microscopy (RCM) enables noninvasive mite detection in rosacea. Objective scoring of rosacea severity is currently lacking. To determine the value of RCM for monitoring , inflammation and vascular parameters in rosacea during treatment. In 20 rosacea patients, clinical and RCM examination were performed before, during, and 12 weeks after a 16-week treatment course with topical ivermectin. Using RCM, number of mites and inflammatory cells, epidermal thickness, and vascular density and diameter were measured. RCM features were correlated with clinical assessment. Treatment resulted in clinical reduction of inflammatory lesions. Mites were detected in 80% of patients at baseline, 30% at week 16, and 63% at week 28. The number of mites reduced significantly during treatment, but no changes in inflammatory cells, epidermal thickness or vascular parameters were observed. Correlation between number of inflammatory lesions and mites was low. None of the RCM variables were significant predictors for clinical success.: RCM enables anti-inflammatory effect monitoring of topical ivermectin by determining mite presence. Quantifying exact mite number, and inflammatory and vascular characteristics is challenging due to device limitations. In its current form, RCM seems of limited value for noninvasive follow-up of rosacea in clinical practice.
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http://dx.doi.org/10.1080/09546634.2020.1741501DOI Listing
March 2020

A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk.

Br J Clin Pharmacol 2020 08 14;86(8):1642-1653. Epub 2020 Apr 14.

Center for Research and Innovation in Clinical Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Lausanne University Hospital and University of Lausanne, University of Geneva, Switzerland.

Background And Objectives: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed.

Methods: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation.

Results: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average.

Conclusion: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.
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http://dx.doi.org/10.1111/bcp.14278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373710PMC
August 2020

A Robotic Biopsy Endoscope with Magnetic 5-DOF Locomotion and a Retractable Biopsy Punch.

Micromachines (Basel) 2020 Jan 17;11(1). Epub 2020 Jan 17.

Department of Mechanical Engineering, Chonnam National University, Gwangju 61186, Korea.

Capsule endoscopes (CEs) have emerged as an advanced diagnostic technology for gastrointestinal diseases in recent decades. However, with regard to robotic motions, they require active movability and multi-functionalities for extensive, untethered, and precise clinical utilization. Herein, we present a novel wireless biopsy CE employing active five degree-of-freedom locomotion and a biopsy needle punching mechanism for the histological analysis of the intestinal tract. A medical biopsy punch is attached to a screw mechanism, which can be magnetically actuated to extrude and retract the biopsy tool, for tissue extraction. The external magnetic field from an electromagnetic actuation (EMA) system is utilized to actuate the screw mechanism and harvest biopsy tissue; therefore, the proposed system consumes no onboard energy of the CE. This design enables observation of the biopsy process through the capsule's camera. A prototype with a diameter of 12 mm and length of 30 mm was fabricated with a medical biopsy punch having a diameter of 1.5 mm. Its performance was verified through numerical analysis, as well as in-vitro and ex-vivo experiments on porcine intestine. The CE could be moved to target lesions and obtain sufficient tissue samples for histological examination. The proposed biopsy CE mechanism utilizing punch biopsy and its wireless extraction-retraction technique can advance untethered intestinal endoscopic capsule technology at clinical sites.
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http://dx.doi.org/10.3390/mi11010098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020148PMC
January 2020

Transferring Racial/Ethnic Marketing Strategies From Tobacco to Food Corporations: Philip Morris and Kraft General Foods.

Am J Public Health 2020 03 16;110(3):329-336. Epub 2020 Jan 16.

All of the authors are with the Philip R. Lee Institute for Health Policy Studies, School of Medicine, University of California San Francisco (UCSF), San Francisco.

To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a "fully integrated" minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.
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http://dx.doi.org/10.2105/AJPH.2019.305482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002936PMC
March 2020

Technical considerations for approaches to the ultrasound-guided maxillary nerve block via the pterygopalatine fossa: a literature review.

Reg Anesth Pain Med 2020 04 9;45(4):301-305. Epub 2020 Jan 9.

Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background And Objectives: Blockade of the trigeminal nerve and its branches is an effective diagnostic tool and potential treatment of facial pain. Ultrasound-guided injections in the pterygopalatine fossa (PPF) to block the trigeminal nerve divisions and sphenopalatine ganglion have been described but a consensus has yet to be reached over the ideal approach. We sought to delineate and compare the various approaches to the ultrasound-guided trigeminal divisions blockade via the PPF.

Methods: The literature search was performed by searching the National Library of Medicine's PubMed database, the Cochrane Database of Systematic Reviews and Google Scholar within the date range of January 2009-March 2019 for keywords targeted toward "trigeminal nerve," "maxillary nerve," or "pterygopalatine fossa," "ultrasound," and "nerve block," using an English language restriction. Six papers were included in the final review: one prospective double-blinded randomized controlled trial, one prospective descriptive study, one case series, two case reports, and one cadaveric study.

Results: There are three main approaches to the ultrasound-guided trigeminal nerve branches blockade via the PPF: anterior infrazygomatic in-plane, posterior infrazygomatic in-plane, and suprazygomatic out-of-plane approaches. Each showed injectate spread to the PPF in cadaver, adult and pediatric patients, respectively.1-5 Injectate used varied from 3 to 5 mL to 0.15 mL/kg.

Conclusions: These studies demonstrated that the PPF is a readily accessible target for the ultrasound-guided maxillary nerve block via three main approaches.2 The ideal approach is yet to be determined and must be further explored.
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http://dx.doi.org/10.1136/rapm-2019-100569DOI Listing
April 2020

Workplace stress and resilience in the Australian nursing workforce: A comprehensive integrative review.

Int J Ment Health Nurs 2020 Feb;29(1):5-34

Hunter New England Local Health District, Newcastle, New South Wales, Australia.

This integrative review aimed to identify and synthesize evidence on workplace stress and resilience in the Australian nursing workforce. A search of the published literature was conducted using EMBASE, MEDLINE, CINAHL (EBSCO), PsycINFO, Web of Science, and Scopus. The search was limited to papers published in English from January 2008 to December 2018. The review integrated both qualitative and quantitative data into a single synthesis. Of the 41 papers that met the inclusion criteria, 65.85% (27/41) used quantitative data, 29.26% (12/41) used qualitative data, and 4.87% (2/41) used mixed methods. About 48.78% (20/41) of the papers addressed resilience issues, 46.34% (19/41) addressed workplace stress, and 4.87% (2/41) addressed both workplace stress and resilience. The synthesis indicated that nurses experience moderate to high levels of stress. Several individual attributes and organizational resources are employed by nurses to manage workplace adversity. The individual attributes include the use of work-life balance and organizing work as a mindful strategy, as well as self-reliance, passion and interest, positive thinking, and emotional intelligence as self-efficacy mechanisms. The organizational resources used to build resilience are support services (both formal and informal), leadership, and role modelling. The empirical studies on resilience largely address individual attributes and organizational resources used to build resilience, with relatively few studies focusing on workplace interventions. Our review recommends that research attention be devoted to educational interventions to achieve sustainable improvements in the mental health and wellbeing of nurses.
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http://dx.doi.org/10.1111/inm.12662DOI Listing
February 2020

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes.

Proc Natl Acad Sci U S A 2020 01 23;117(1):563-572. Epub 2019 Dec 23.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB-up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.
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http://dx.doi.org/10.1073/pnas.1915770117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955337PMC
January 2020