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1.
SAGE Open Med ; 12: 20503121231223467, 2024.
Article in English | MEDLINE | ID: mdl-38249955

ABSTRACT

Introduction: To decrease the risk of complications from ventilator-associated pneumonia, it is essential to implement preventative measures in all ICU patients. Since 2018, with the help of Japanese experts, we have applied a ventilator-associated pneumonia care bundle with 10 basic standards in patient care and monitoring. Therefore, we conducted a study to evaluate the results of applying 10 solutions to prevent ventilator-associated pneumonia over 24 months. Methods: A cross-sectional descriptive study with longitudinal follow-up for 24 months on 170 mechanically ventilated patients at the Center for Critical Care Medicine, Bach Mai Hospital. According to the Centers for Disease Control (CDC, 2021), the diagnosis of ventilator-associated pneumonia is when pneumonia appears 48 h after intubation by confirmation by at least two doctors. Evaluate compliance with each solution in the care bundle through camera monitoring, medical records, and directly on patients daily. Results: The rate of ventilator-associated pneumonia is 12.9%, the frequency of occurrence is 16.54 of 1000 days. The compliance rate for complete compliance with a 10-item ventilator-associated pneumonia was only 1.8%, while the average value was 84.1%. Average values of compliance with each solution for hand hygiene, head elevation 30-45 degrees, oral hygiene, stopping sedation, breathing circuit management, cuff pressure management, hypoplastic suction, Spontaneous breathing trial (SBT) daily and assessed extubation, mobilization and early leaving bed, ulcer and thrombosis prevention were 96.9%, 97.3%, 99.4%, 81.5%, 99.9%, 99.9%, 86.3%, 83.5%, 49.3%, and 46.4%, respectively. The time to appear ventilator-associated pneumonia in the high compliance group was 46.7 ± 5.0 days, higher than in the low compliance group, 10.3 ± 0.7 days, p < 0.001. Conclusions: A 10-item ventilator-associated pneumonia care bundle has helped reduce the incidence of ventilator-associated pneumonia. To reduce the risk of ventilator-associated pneumonia and shorten ICU and hospital stays, it is essential to fully adhere to subglottic secretion suction, daily SBT, and early mobilization and leaving the bed.

2.
Waste Biomass Valorization ; : 1-10, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37363338

ABSTRACT

Air pollution and infectious diseases (such as the COVID-19 pandemic) have attracted considerable attention from governments and scientists worldwide to find the best solutions to address these issues. In this study, a new simultaneous antibacterial and particulate matter (PM) filtering Ag/graphene-integrated non-woven polypropylene textile was fabricated by simply immersing the textile into a Ag/graphene-containing solution. The Ag/graphene nanocomposite was prepared by reducing Ag ions on the surface of graphene nanoplatelets (GNPs) using the leaf extract. The prepared Ag/graphene textile was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Energy Dispersive X-ray (EDX), and contact angle measurements. The results showed excellent integration of the Ag/GNP nanocomposite into the non-woven polypropylene textile matrix. The prepared textile exhibited superhydrophobicity with a contact angle of 152°. The maximum PM removal percentage of the Ag/GNP-integrated textile was determined to be 98.5% at an Ag/GNP content of 1.5% w/w and a silicon adhesive of 1% w/w. The Ag/GNP textile exhibited high antibacterial activity toward Escherichia coli with no sign of bacteria on the surface. Remarkably, the as-prepared Ag/GNP textile was highly durable and stable and could be reused many times after washing.

3.
Exp Gerontol ; 177: 112184, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37105504

ABSTRACT

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.


Subject(s)
Presbycusis , Animals , Mice , Disease Models, Animal , Presbycusis/prevention & control , Cochlea , Aging/physiology , Lymphocytes
4.
Indian J Dermatol Venereol Leprol ; 89(3): 378-384, 2023.
Article in English | MEDLINE | ID: mdl-36331855

ABSTRACT

Background Generalized pustular psoriasis (GPP) is a chronic disease associated with genetic factors related to mutations of the interleukin 36 receptor antagonist gene (IL36RN) and the caspase recruitment domain 14 gene (CARD14). However, the relevance of these mutations to the clinical features and severity of GPP remains unclear. Aims Our objective was to correlate the presence of IL36RN and CARD14 mutations with the clinical and laboratory findings in patients with GPP. Methods This cross-sectional descriptive study was conducted in 64 subjects with GPP. Clinical manifestations were recorded and the severity was graded as mild, moderate, or severe. Routine laboratory tests were performed and blood samples were collected for Sanger sequencing. The clinical data of patients were compared among the different mutation groups. Results The two main variants of IL36RN were c.115+6T > C (p.Arg10ArgfsX1) and c.227C > T (p.Pro76Leu). The major CARD14 mutations were c.2458C > T (p.Arg820Trp), c.1641C > T (p.Arg547Ser), and c.1753G > A transitions. Provocative factors were uncommon in the group with both IL36RN and CARD14 mutations. Drugs (unspecified), especially herbals, were the most common triggers. A history of psoriasis was frequent in patients with only CARD14 mutations, but fever was uncommon. The c.1641C > T mutation was associated with leukocytosis > 15000/mm3 and the c.1753G > A mutation was associated with hypoalbuminemia <3.8g/dL. Both the c.115+6T > C and c.227C > T variants of IL36RN were associated with fever ≥38.5°C while the c.115+6T > C variant was also associated with geographic tongue. No gene mutations were associated with the total severity and severity grades. Limitations Four patients without the two major IL36RN mutations were excluded from the study. Conclusion The presence of IL36RN and CARD14 mutations were associated with a history of psoriasis, various provocative factors, fever, leukocytosis, hypoalbuminemia, and geographic tongue. Further studies to explore the role of these mutations in therapeutic efficacy and disease outcomes are necessary.


Subject(s)
Glossitis, Benign Migratory , Hypoalbuminemia , Psoriasis , Humans , Interleukins/genetics , Cross-Sectional Studies , Leukocytosis , Psoriasis/diagnosis , Psoriasis/genetics , Psoriasis/drug therapy , Mutation/genetics , Chronic Disease , Guanylate Cyclase/genetics , Membrane Proteins/genetics , CARD Signaling Adaptor Proteins/genetics
5.
Catal Sci Technol ; 12(14): 4511-4523, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35924073

ABSTRACT

The promotional effects on photocatalytic hydrogen production of Cu x O clusters deposited using atomic layer deposition (ALD) on P25 TiO2 are presented. The structural and surface chemistry study of Cu x O/TiO2 samples, along with first principles density functional theory simulations, reveal the strong interaction of ALD deposited Cu x O with TiO2, leading to the stabilization of Cu x O clusters on the surface; it also demonstrated substantial reduction of Ti4+ to Ti3+ on the surface of Cu x O/TiO2 samples after Cu x O ALD. The Cu x O/TiO2 photocatalysts showed remarkable improvement in hydrogen productivity, with 11 times greater hydrogen production for the optimum sample compared to unmodified P25. With the combination of the hydrogen production data and characterization of Cu x O/TiO2 photocatalysts, we inferred that ALD deposited Cu x O clusters have a dual promotional effect: increased charge carrier separation and improved light absorption, consistent with known copper promoted TiO2 photocatalysts and generation of a substantial amount of surface Ti3+ which results in self-doping of TiO2 and improves its photo-activity for hydrogen production. The obtained data were also employed to modify the previously proposed expanding photocatalytic area and overlap model to describe the effect of cocatalyst size and weight loading on photocatalyst activity. Comparing the trend of surface Ti3+ content increase and the photocatalytically promoted area, calculated with our model, suggests that the depletion zone formed around the heterojunction of Cu x O-TiO2 is the main active area for hydrogen production, and the hydrogen productivity of the photocatalyst depends on the surface coverage by this active area. However, the overlap of these areas suppresses the activity of the photocatalyst.

6.
Dermatol Res Pract ; 2022: 9838867, 2022.
Article in English | MEDLINE | ID: mdl-35492738

ABSTRACT

Objective: To evaluate the efficacy and safety of the combination of metformin and methotrexate (MTX) versus MTX monotherapy in treating psoriasis in patients with metabolic syndrome. Materials and Methods: A prospective clinical trial was conducted using metformin and MTX to treat psoriasis patients with metabolic syndrome. A treatment group of 35 psoriasis patients with metabolic syndrome was treated with MTX and metformin. A control group of 31 psoriasis patients with metabolic syndrome was treated with MTX only. Results: Patients treated with the combined regimen showed measured improvement in disease status compared to those treated with MTX monotherapy. The Psoriasis Area and Severity Index (PASI) scores of psoriasis patients with metabolic syndrome using the metformin and MTX combination were significantly lower than those treated with MTX only (p < 0.05). The combination treatment group also showed a significant decrease in blood sugar and triglyceride levels after 3 months (p < 0.05). However, there were no significant differences in subclinical indexes between the treatment and control groups. Conclusion: In this treatment sample, a combination of metformin and MTX in psoriasis patients with metabolic syndrome showed positive responses and no serious side effects.

7.
J Am Soc Nephrol ; 33(4): 850-866, 2022 04.
Article in English | MEDLINE | ID: mdl-35361724

ABSTRACT

BACKGROUND: Concerns regarding cardiovascular safety with current treatments for anemia in patients with dialysis-dependent (DD)-CKD have encouraged the development of alternatives. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis by increasing endogenous erythropoietin and iron availability. METHODS: In this open-label phase 3 study, patients with DD-CKD and anemia were randomized 1:1 to oral roxadustat three times weekly or parenteral epoetin alfa per local clinic practice. Initial roxadustat dose depended on erythropoiesis-stimulating agent dose at screening for patients already on them and was weight-based for those not on them. The primary efficacy end point was mean hemoglobin change from baseline averaged over weeks 28‒52 for roxadustat versus epoetin alfa, regardless of rescue therapy use, tested for noninferiority (margin, -0.75 g/dl). Adverse events (AEs) were assessed. RESULTS: Among 2133 patients randomized (n=1068 roxadustat, n=1065 epoetin alfa), mean age was 54.0 years, and 89.1% and 10.8% were on hemodialysis and peritoneal dialysis, respectively. Mean (95% confidence interval) hemoglobin change from baseline was 0.77 (0.69 to 0.85) g/dl with roxadustat and 0.68 (0.60 to 0.76) g/dl with epoetin alfa, demonstrating noninferiority (least squares mean difference [95% CI], 0.09 [0.01 to 0.18]; P<0.001). The proportion of patients experiencing ≥1 AE and ≥1 serious AE was 85.0% and 57.6% with roxadustat and 84.5% and 57.5% with epoetin alfa, respectively. CONCLUSIONS: Roxadustat effectively increased hemoglobin in patients with DD-CKD, with an AE profile comparable to epoetin alfa. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis. CLINICALTRIALS: gov Identifier: NCT02174731.


Subject(s)
Anemia , Renal Insufficiency, Chronic , Anemia/drug therapy , Anemia/etiology , Epoetin Alfa/therapeutic use , Glycine/analogs & derivatives , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases , Isoquinolines , Middle Aged , Renal Dialysis , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/therapy
8.
Invest Ophthalmol Vis Sci ; 63(3): 25, 2022 03 02.
Article in English | MEDLINE | ID: mdl-35348589

ABSTRACT

Purpose: To evaluate changes in the retinal microvasculature of young adults over 24 hours using optical coherence tomography angiography (OCT-A). Methods: Participants (n = 44, mean age 23.2 ± 4.1 years, 24 myopes and 20 nonmyopes) with normal ophthalmological findings were recruited. Two macular OCT-A and OCT scans, systemic blood pressure, intraocular pressure (IOP), and biometry measurements were taken every four hours over 24 hours. Superficial and deep retinal layer en face images were analyzed to extract magnification-corrected vascular indexes using image analysis including foveal avascular zone metrics, vessel density, and perfusion density for the foveal, parafoveal, and perifoveal zones. Results: Significant diurnal variations (P < 0.001) were observed in the vessel and perfusion density in the three superficial retinal layer regions, with acrophase between 4:30 PM and 8:30 PM. Only foveal and parafoveal regions of the deep retinal layer exhibited significant diurnal variations with acrophase between 9 AM and 3 PM. Myopes and nonmyopes had different acrophases but not amplitudes in the parafoveal perfusion density of superficial retinal layer (P = 0.039). Significant correlations were observed between diurnal amplitudes or acrophases of superficial retinal layer indexes and systemic pulse pressure, IOP, axial length and retinal thickness. Conclusions: This study shows, for the first time, that significant diurnal variation exists in OCT-A indexes of macular superficial and deep retinal layer over 24 hours and were related to variations in various ocular and systemic measurements. Myopes and nonmyopes showed differences in the timing but not in amplitude of the superficial retinal layer parafoveal perfusion density variations but not in deep retinal layer.


Subject(s)
Macula Lutea , Tomography, Optical Coherence , Adult , Fluorescein Angiography/methods , Fovea Centralis/blood supply , Humans , Macula Lutea/blood supply , Retinal Vessels , Tomography, Optical Coherence/methods , Young Adult
9.
Nanotechnology ; 33(6)2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34654008

ABSTRACT

Highly responsive methanol sensors working at low temperatures are developed using hierarchical ZnO nanorods decorated by Pt nanoparticles. The sensing materials are fabricated following a 3-step process: electrospinning of ZnO nanofibers, hydrothermal growth of hierarchical ZnO nanorods on the nanofibers and UV-assisted deposition of Pt nanoparticles. The morphology, structure and properties of the materials are examined by field-effect scanning electron microscopy, transmission electron microscope, x-ray diffraction, x-ray photoelectron spectroscopy, UV-Vis absorption spectroscopy, and electrical measurements. The methanol sensing performance is investigated at different working temperatures in the range of 110 °C-260 °C. It is observed that the surface modification of the ZnO hierarchical nanorods by Pt nanoparticles results in a remarkable enhancement of the sensing response toward methanol, which can reach approximately 19 500 times higher than that of the unmodified ZnO nanorods-based sensor. In addition, this modification enables lower working temperatures with an optimum range of 140 °C-200 °C. Based on the achieved results, a methanol sensing mechanism of the Pt/ZnO structure is proposed.

10.
Sci Rep ; 11(1): 18924, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34556710

ABSTRACT

Sepsis is the most common cause of in-hospital deaths, especially from low-income and lower-middle-income countries (LMICs). This study aimed to investigate the mortality rate and associated factors from sepsis in intensive care units (ICUs) in an LMIC. We did a multicenter cross-sectional study of septic patients presenting to 15 adult ICUs throughout Vietnam on the 4 days representing the different seasons of 2019. Of 252 patients, 40.1% died in hospital and 33.3% died in ICU. ICUs with accredited training programs (odds ratio, OR: 0.309; 95% confidence interval, CI 0.122-0.783) and completion of the 3-h sepsis bundle (OR: 0.294; 95% CI 0.083-1.048) were associated with decreased hospital mortality. ICUs with intensivist-to-patient ratio of 1:6 to 8 (OR: 4.533; 95% CI 1.621-12.677), mechanical ventilation (OR: 3.890; 95% CI 1.445-10.474) and renal replacement therapy (OR: 2.816; 95% CI 1.318-6.016) were associated with increased ICU mortality, in contrast to non-surgical source control (OR: 0.292; 95% CI 0.126-0.678) which was associated with decreased ICU mortality. Improvements are needed in the management of sepsis in Vietnam such as increasing resources in critical care settings, making accredited training programs more available, improving compliance with sepsis bundles of care, and treating underlying illness and shock optimally in septic patients.


Subject(s)
Intensive Care Units/statistics & numerical data , Sepsis/mortality , Aged , Cross-Sectional Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Risk Assessment/statistics & numerical data , Risk Factors , Sepsis/therapy , Vietnam/epidemiology
11.
Anim Reprod Sci ; 232: 106825, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34418612

ABSTRACT

There was examination of effects of accessory corpus lutea (CLs) formation and regression during pregnancy on circulating progesterone (P4) concentrations and pregnancy maintenance in beef heifers. Heifers (Experiment 1, n = 75; Experiment 2, n = 496) were randomly assigned to either a human chorionic gonadotropin (hCG) treatment or untreated group 5 days post-estrus, followed by embryo transfer (ET) on Days 6-8 (Day 0 = Estrus). In Experiment 1, blood samples were collected from pregnant heifers on Days 33, 40, and 47 for conducting P4 assays. Plasma P4 concentrations were greater in hCG-treated heifers than in untreated heifers on Day 33. In hCG-treated heifers with accessory CL regression between Days 33 and 47, plasma P4 decreased to concentrations similar to those of untreated heifers after Day 40. In hCG-treated pregnant heifers in Experiment 2, CL regression by Day 50 of gestation was more frequent when CLs were contralateral (49.3 %) rather than ipsilateral (4.4 %, P < 0.001) to the original CL. The hCG treatment resulted in a greater pregnancy percentages on Days 30 (80.5 % and 68.6 %, P = 0.002) and 50 (76.2 % and 65.3 %, P = 0.007) compared with untreated heifers. There, however, were no differences in either pregnancy percentages on Days 30 and 50 or pregnancy losses between hCG-treated heifers with ipsilateral and contralateral accessory CLs. These results indicate accessory CL formation improves pregnancy percentages resulting from ET. Furthermore, plasma P4 decreases associated with accessory CL regression does not affect pregnancy loss in beef heifers.


Subject(s)
Cattle/physiology , Corpus Luteum/physiology , Pregnancy, Animal , Progesterone/blood , Animals , Cattle/blood , Chorionic Gonadotropin/pharmacology , Embryo Transfer , Female , Pregnancy , Pregnancy, Animal/blood , Pregnancy, Animal/physiology , Progesterone/metabolism
12.
PLoS One ; 16(8): e0256589, 2021.
Article in English | MEDLINE | ID: mdl-34415963

ABSTRACT

BACKGROUND: The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. METHODS: Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. RESULTS: Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. CONCLUSION: There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.


Subject(s)
Body Mass Index , Waist Circumference , Adult , Aged , Asian People , Female , Humans , Male , Middle Aged , Risk Factors , Sex Characteristics
13.
J Cutan Aesthet Surg ; 14(1): 101-106, 2021.
Article in English | MEDLINE | ID: mdl-34084016

ABSTRACT

BACKGROUND: Melasma is an acquired and treatment-resistant aging facial skin condition prevalent among the older Asian females. The Q-switched toning laser is the most widely used for the treatment of moderate to severe melasma in Asia. Recently, the picosecond laser has been introduced for various pigmentary disorders such as melasma. We evaluated the efficacy and safety of dual toning combined with 1064 nm Nd:YAG picosecond and quasi-long-pulsed laser in the treatment of severe melasma. SUBJECTS AND METHODS: Twenty Vietnamese females, mean age 41.9 ± 6.4 years, Fitzpatrick skin type IV, with clinical diagnosis of severe dermal and mixed-type melasma were treated by at least eight sessions picosecond Nd:YAG 1064 nm reducing Melasma Area and Severity Index (MASI) to less than 15%. Then they were treated with 3 sessions of dual toning combined picosecond Nd:YAG 1064 nm laser having an energy and spot size of 0.6-0.8 J/cm2 and 8 mm with micropulsed mode Nd:YAG 1064 nm laser (350 µs) having an energy and spot size of 2.6 J/cm2 and 15 mm with ICD off. Mild and even erythema was the endpoint (40-42°C using the infrared thermometer). Treatments were given every 4 weeks. Improvement was rated by MASI at the baseline (T1), after eight sessions of picotoning (T2), and three sessions of dual toning (T3). RESULTS: The mean MASI score of 20 patients at baseline (T1) was 16.24 ± 4.88 (min 6.0; max 28.8); after at least eight picotoning sessions, the mean MASI was 15.12 ± 4.69, representing a 7.44 ± 4.41% reduction in MASI score. The MASI score of the dual toning laser continued to decrease after three dual toning sessions from 15.12 ± 4.6 to 9.77 ± 3.86 (MASI score reduced by a mean of 5.35 ± 2.64), achieving 35.15 ± 13.51% reduction from T2 and 40.17 ± 12.14% reduction from baseline MASI (T1). There were no unexpected side effects in any patients. CONCLUSION: The dual toning method using the 1064 nm Nd:YAG picosecond and microsecond laser was safe and effective and well tolerated by all patients without downtime. However, larger number of studies should be conducted with more objective measurement techniques to confirm the results of this preliminary study.

14.
J Neuroimmunol ; 357: 577628, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34130076

ABSTRACT

We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4+ T cell fractions, namely, naturally occurring regulatory T cells (Treg), interleukin 1 receptor type 2-expressing T cells (I1R2), and non-Treg non-I1R2 (nTnI) cells, which comprised Treg and I1R2-deleted CD4+ T cells. Inoculation of the nTnI fraction into a ARHL murine model, not only prevented the development of ARHL and the degeneration of spiral ganglion neurons, but also suppressed serum nitric oxide, a source of oxidative stress. Further investigations on CD4+ T cell fractions could provide novel insights into the prevention of aging, including presbycusis.


Subject(s)
CD4-Positive T-Lymphocytes/transplantation , Presbycusis/immunology , Presbycusis/prevention & control , T-Lymphocyte Subsets/transplantation , Animals , CD4-Positive T-Lymphocytes/immunology , Disease Models, Animal , Disease Progression , Mice , Receptors, Interleukin-1 Type II/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology
15.
J Am Soc Nephrol ; 32(6): 1537-1538, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33849916
16.
J Am Soc Nephrol ; 32(3): 737-755, 2021 03.
Article in English | MEDLINE | ID: mdl-33568383

ABSTRACT

BACKGROUND: Current anemia therapies for patients with non-dialysis-dependent CKD may require injection and medical visits. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis and improves iron homeostasis. METHODS: In this double-blind phase 3 study, we randomized patients with non-dialysis-dependent CKD stages 3-5 and hemoglobin <10.0 g/dl (1:1) to thrice-weekly 70-mg oral roxadustat or placebo. Doses were titrated throughout the study based on hemoglobin levels. The primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52 versus placebo, irrespective of rescue therapy use. We assessed patients for adverse events. RESULTS: The study included 2781 patients, 1393 who received roxadustat and 1388 who received placebo. Mean baseline hemoglobin was 9.1 g/dl for both groups. The mean change in hemoglobin from baseline was 1.75 g/dl (95% confidence interval [95% CI], 1.68 to 1.81) with roxadustat versus 0.40 g/dl (95% CI, 0.33 to 0.47) with placebo, (P<0.001). Among 411 patients with baseline elevated high-sensitivity C-reactive protein, mean change in hemoglobin from baseline was 1.75 g/dl (95% CI, 1.58 to 1.92) with roxadustat versus 0.62 g/dl (95% CI, 0.44 to 0.80) with placebo, (P<0.001). Roxadustat reduced the risk of red blood cell transfusion by 63% (hazard ratio, 0.37; 95% CI, 0.30 to 0.44). The most common adverse events with roxadustat and placebo, respectively, were ESKD (21.0% versus 20.5%), urinary tract infection (12.8% versus 8.0%), pneumonia (11.9% versus 9.4%), and hypertension (11.5% versus 9.1%). CONCLUSIONS: Roxadustat effectively increased hemoglobin in patients with non-dialysis-dependent CKD and reduced the need for red blood cell transfusion, with an adverse event profile comparable to that of placebo. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With CKD, Not on Dialysis, NCT02174627.


Subject(s)
Anemia/drug therapy , Anemia/etiology , Glycine/analogs & derivatives , Hematinics/therapeutic use , Isoquinolines/therapeutic use , Prolyl-Hydroxylase Inhibitors/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Aged , Anemia/blood , Double-Blind Method , Endpoint Determination , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/metabolism , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Isoquinolines/adverse effects , Male , Middle Aged , Prolyl-Hydroxylase Inhibitors/adverse effects , Renal Insufficiency, Chronic/blood , Safety
18.
Eye (Lond) ; 35(3): 973-978, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32518400

ABSTRACT

BACKGROUND: To compare functional staging classifications in Vietnamese patients with primary open angle glaucoma (POAG) and chronic primary angle closure glaucoma (PACG). METHODS: A retrospective cross-section study was conducted at a national setting. Two hundred seven eyes of 207 patients were recruited. Patients were tested with standard automated perimetry. Field loss was generally classified in four stages (normal, early, moderate, and severe), using four classification strategies: (1) Hodapp-Parrish-Anderson (HPA), (2) enhanced Glaucoma Staging System (eGSS), (3) modified Glaucoma Staging System (mGSS) and (4) the Advanced Glaucoma Intervention Study (AGIS). AGIS as a standard method was used to judge the staging performance of the other three classifications in terms of agreement (Cohen Kappa-K) and association (Chi-Square Test-Cramer's V). RESULTS: The agreement between AGIS and mGSS (K = 0.687; p < 0.001) and HPA (K = 0.686; p < 0.001) was substantial while that between AGIS and eGSS was slight (K = 0.103; p < 0.001). The association between AGIS and mGSS (V = 0.748; p < 0.001) and HPA (V = 0.748; p < 0.001) was greater than eGSS (V = 0.594; p < 0.001). CONCLUSIONS: MGSS and HPA showed stronger agreement and closer association with AGIS than eGSS. We recommend mGSS should be used in managing a glaucoma clinic because of its simplicity and convenience over HPA and AGIS.


Subject(s)
Glaucoma, Angle-Closure , Glaucoma, Open-Angle , Glaucoma , Asian People , Humans , Intraocular Pressure , Retrospective Studies , Vision Disorders , Visual Field Tests , Visual Fields
19.
Exp Cell Res ; 398(1): 112390, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33227314

ABSTRACT

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.


Subject(s)
Antineoplastic Agents/pharmacology , Gamma Rays , Phenylurea Compounds/pharmacology , Protein Kinase Inhibitors/pharmacology , Quinolines/pharmacology , Thyroid Neoplasms/therapy , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Combined Modality Therapy , Female , Humans , Mice , Mice, Congenic , Mice, Nude , Neoplasms, Experimental/pathology , Neoplasms, Experimental/therapy , Thyroid Neoplasms/pathology , Tumor Cells, Cultured
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