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Chronic Diseases and Translational... Mar 2024[This corrects the article DOI: 10.1002/cdt3.13.].
Corrigendum: Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority phase III trail.
[This corrects the article DOI: 10.1002/cdt3.13.].
PubMed: 38450310
DOI: 10.1002/cdt3.93 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment...
PURPOSE
Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of glaucoma with the causative drugs using a spontaneous reporting system database.
METHODS
Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on reports of glaucoma caused by all drugs, we calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for glaucoma.
RESULTS
Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate. Among 207 reports involved in angle-closure glaucoma (86%, women), anticholinergic drug and antidepressants ranked high and showed signals. Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma.
CONCLUSION
A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it.
PubMed: 38050555
DOI: 10.2147/OPTH.S439255 -
Advances in Therapy Oct 2021Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD).... (Randomized Controlled Trial)
Randomized Controlled Trial
Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES).
INTRODUCTION
Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with end-stage kidney disease on dialysis for at least 4 months.
METHODS
Patients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0-12.0 g/dL during the treatment period (day 1 up to 52-104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28-36 without rescue therapy and hemoglobin CFB to the average of weeks 28-52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively.
RESULTS
Of 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat - ESA) for hemoglobin CFB to weeks 28-36 (without rescue therapy) and CFB to weeks 28-52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating non-inferiority of roxadustat to ESA (non-inferiority margin of - 0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28-36 were 84.2% (roxadustat) and 82.4% (ESA). Roxadustat was superior to ESA in decreasing LDL cholesterol from baseline to the average of weeks 12-28. Serious TEAEs occurred in 50.7% (roxadustat) and 45.0% (ESA) of patients. Common TEAEs in both treatment groups included hypertension, arteriovenous fistula thrombosis, headache, and diarrhea.
CONCLUSION
Roxadustat was non-inferior to ESAs in maintaining hemoglobin levels in this cohort of patients with anemia of CKD on dialysis for at least 4 months who were previously treated with ESAs. Observed TEAEs were consistent with previous studies.
Topics: Anemia; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Research Design
PubMed: 34537926
DOI: 10.1007/s12325-021-01904-6 -
Journal of Clinical Laboratory Analysis Apr 2022Some streptococci strains identified as Streptococcus pneumoniae (S. pneumoniae) by routine clinical methods exhibiting negative Quellung reaction results may belong to...
BACKGROUND
Some streptococci strains identified as Streptococcus pneumoniae (S. pneumoniae) by routine clinical methods exhibiting negative Quellung reaction results may belong to other species of viridans group streptococci or non-typeable S. pneumoniae. The purpose of this study was to investigate the identification and molecular characteristics of S. pneumoniae with negative Quellung reaction results.
METHODS
One hundred and five isolates identified as S. pneumoniae using routine microbiological methods with negative Quellung reaction results were included. Multilocus sequence analysis (MLSA) was used as a gold standard in species identification, and the capacity of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in identification was evaluated. Capsular genes and sequence types of S. pneumoniae isolates were determined by sequential multiplex PCR and multilocus sequence typing. Antimicrobial susceptibility patterns were determined via broth microdilution with a commercialized 96-well plate.
RESULTS
Among the isolates, 81 were identified as S. pneumoniae and 24 were S. pseudopneumoniae by MLSA. MALDI-TOF MS misidentified six S. pneumoniae isolates as S. pseudopneumoniae and nine S. pseudopneumoniae isolates as S. pneumoniae or S. mitis/S. oralis. Thirty-one sequence types (STs) were detected for these 81 S. pneumoniae isolates, and the dominant ST was ST-bj12 (16, 19.8%). The non-susceptibility rates of S. pseudopneumoniae were comparable to those of NESp strains.
CONCLUSIONS
Some S. pneumoniae isolates identified by routine methods were S. pseudopneumoniae. Most NESp strains have a different genetic background compared with capsulated S. pneumoniae strains. The resistance patterns of S. pseudopneumoniae against common antibiotics were comparable to those of NESp.
Topics: Darbepoetin alfa; Humans; Molecular Epidemiology; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptococcus; Streptococcus pneumoniae
PubMed: 35170080
DOI: 10.1002/jcla.24293 -
Clinical and Experimental Nephrology Sep 2022Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia of chronic kidney disease (CKD). This post hoc analysis of a Japanese,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia of chronic kidney disease (CKD). This post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in patients with non-dialysis-dependent (NDD) CKD evaluated disease state-related parameters among patients with and without diabetes mellitus who received roxadustat. In the 1517-CL-0310 study (NCT02988973), roxadustat was noninferior to darbepoetin alfa for change in average hemoglobin levels at Weeks 18-24 from baseline who received roxadustat.
METHODS
Patients enrolled in the 1517-CL-0310 study who received roxadustat were included in this post hoc analysis. Hematologic (hemoglobin, reticulocyte/erythrocyte ratio, mean corpuscular volume [MCV], and mean corpuscular hemoglobin [MCH]), iron-related (ferritin, total iron-binding capacity, transferrin, ceruloplasmin, and hepcidin), metabolic (HbA1c, glycated albumin, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), and renal (eGFR) parameters were summarized descriptively by visit through Week 52.
RESULTS
Among 201 included patients, 105 (52.2%) and 96 (47.8%) were in the Diabetes and No Diabetes subgroups, respectively. There were no clinically meaningful differences through Week 52 for most hematologic, iron-related, metabolic, or renal parameters between patients in the Diabetes and No Diabetes subgroups. MCV and MCH remained lower and HbA1c and glycated albumin remained higher in patients in the Diabetes subgroup through Week 52. Both subgroups experienced a similar benefit from roxadustat in maintaining hemoglobin levels in the target range of 10-12 g/dL.
CONCLUSION
Roxadustat maintained hemoglobin levels in the target range with similar clinical parameters irrespective of diabetes mellitus presence at baseline.
Topics: Anemia; Cholesterol; Diabetes Mellitus; Glycated Hemoglobin; Glycine; Hemoglobins; Humans; Iron; Isoquinolines; Japan; Renal Insufficiency, Chronic
PubMed: 35462610
DOI: 10.1007/s10157-022-02225-w -
Kidney International Reports Jul 2021Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with...
INTRODUCTION
Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (noninferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis.
METHODS
Erythropoiesis-stimulating agent (ESA)-naïve patients and ESA-treated patients were randomized at a 1:1 ratio to receive enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks for 24 weeks, respectively. Subjects in each arm had dose adjustments every 4 weeks to maintain their hemoglobin (Hb) level within the target range (10 to 12 g/dl). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as weeks 20 to 24 (noninferiority margin: -0.75 g/dl).
RESULTS
The mean Hb level during the evaluation period in the enarodustat arm was 10.96 g/dl (95% confidence interval [CI]: 10.84 to 11.07 g/dl) with a difference of 0.09 g/dl (95% CI: -0.07 to 0.26 g/dl) between arms, establishing its noninferiority to DA. Nearly 90% of subjects in both arms maintained a mean Hb level within the target range. Compared with DA, enarodustat was associated with decreased hepcidin and ferritin, and increased total iron-binding capacity. There were no apparent differences in the incidence of adverse events between arms (65.4% [enarodustat], 82.6% [DA]).
CONCLUSIONS
The efficacy of enarodustat was comparable to DA in anemic patients with CKD not requiring dialysis. No new safety concerns were identified compared with DA.
PubMed: 34307978
DOI: 10.1016/j.ekir.2021.04.037 -
Cureus Jan 2023Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases...
Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases as vaccines. Though various biologic drugs are already available, they are still not within reach of the common man due to financial constraints. Through many search engines, studies evaluating the cost variation of different brands of biologics were investigated; however, only a few studies that address this problem were found. Hence, this study was planned with the objective of addressing the cost variation of various brands of biologic medicines available in the Indian market. Methods The website for the Current Index of Medical Specialties (CIMS) for India's location was used to obtain the prices of the different brands of biologic medicines in Indian National Rupee (INR) currency, which different manufacturers market with identical forms in strength and dosage. The percentage cost variation and cost ratio were calculated with the help of the minimum and maximum prices of various brands of biologic drugs. Results The prices of biologics belonging to six different classes that are available in 23 formulations were analyzed. The highest cost variability was shown by pegfilgrastim 6 mg at 1,022.92%, and the minimum-cost variation was shown by darbepoetin alfa 200 mcg at 13.07%. Conclusion Our research found a vast variance in the costs of various brands of biologic medicines in India. The government should address this cost variation problem by developing various policies, such as breaking the monopoly of manufacturers, providing tax incentives to nonprofit generic medicine manufacturers, and incorporating more biologic drugs under the protection of the Drugs Prices Control Order (DPCO).
PubMed: 36820122
DOI: 10.7759/cureus.33943 -
International Journal of Infectious... Jul 2022Nonencapsulated Streptococcus pneumoniae (NESp) is emerging after the introduction of pneumococcal conjugate vaccines (PCVs). This study aimed to elucidate the genetic...
OBJECTIVES
Nonencapsulated Streptococcus pneumoniae (NESp) is emerging after the introduction of pneumococcal conjugate vaccines (PCVs). This study aimed to elucidate the genetic characteristics of penicillin-binding proteins (PBPs; PBP1a, 2b, and 2x) associated with penicillin nonsusceptibility in emergent NESp.
METHODS
A total of 71 NESp isolates that were identified in our previous study during the PCV era in Japan (2011-2019) were analyzed for their amino acid sequences of transpeptidase domain in PBP 1a, 2b, and 2x.
RESULTS
Overall, we identified 21 different PBP profiles (1a-2b-2x), all of which represent novel PBP profiles. The dominant PBP profiles were 13-16-ne1 (32.4%, n = 23), ne1-16-ne2 (14.1%, n = 10), and 13-7-ne4 (7.0%, n = 5) (novel PBP type was numbered with "ne" denoting "nonencapsulated"), accounting for 53.5% of all isolates. All isolates with the PBP profiles 13-16-ne1 and 13-7-ne4 and those having PBP1a type-13 and -131, PBP2b type-7, -ne1, and -ne2 showed nonsusceptibility to penicillin. A high degree of genetic diversity was found in PBP2x, with most of them (81.7%) being new types.
CONCLUSIONS
Our current study identified the 21 novel PBP profiles and remarkable mutations in the PBPs, which may be potentially associated with penicillin nonsusceptibility in NESp.
Topics: Aminoacyltransferases; Bacterial Proteins; Darbepoetin alfa; Humans; Japan; Microbial Sensitivity Tests; Penicillin Resistance; Penicillin-Binding Proteins; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 35470022
DOI: 10.1016/j.ijid.2022.04.033 -
Journal of Bone and Mineral Research :... Sep 2022Pseudohypoparathyroidism type Ib (PHP1B) is characterized predominantly by resistance to parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. These...
Targeted Long-Read Sequencing Identifies a Retrotransposon Insertion as a Cause of Altered GNAS Exon A/B Methylation in a Family With Autosomal Dominant Pseudohypoparathyroidism Type 1b (PHP1B).
Pseudohypoparathyroidism type Ib (PHP1B) is characterized predominantly by resistance to parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. These laboratory abnormalities are caused by maternal loss-of-methylation (LOM) at GNAS exon A/B, which reduces in cis expression of the stimulatory G protein α-subunit (Gsα). Paternal Gsα expression in proximal renal tubules is silenced through unknown mechanisms, hence LOM at exon A/B reduces further Gsα protein in this kidney portion, leading to PTH resistance. In a previously reported PHP1B family, affected members showed variable LOM at exon A/B, yet no genetic defect was found by whole-genome sequencing despite linkage to GNAS. Using targeted long-read sequencing (T-LRS), we discovered an approximately 2800-bp maternally inherited retrotransposon insertion nearly 1200 bp downstream of exon XL not found in public databases or in 13,675 DNA samples analyzed by short-read whole-genome sequencing. T-LRS data furthermore confirmed normal methylation at exons XL, AS, and NESP and showed that LOM comprising exon A/B is broader than previously thought. The retrotransposon most likely causes the observed epigenetic defect by impairing function of a maternally derived NESP transcript, consistent with findings in mice lacking full-length NESP mRNA and in PHP1B patients with deletion of exon NESP and adjacent intronic sequences. In addition to demonstrating that T-LRS is an effective strategy for identifying a small disease-causing variant that abolishes or severely reduces exon A/B methylation, our data demonstrate that this sequencing technology has major advantages for simultaneously identifying structural defects and altered methylation. © 2022 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Chromogranins; DNA Methylation; Darbepoetin alfa; Exons; GTP-Binding Protein alpha Subunits, Gs; Mice; Pseudohypoparathyroidism; Retroelements
PubMed: 35811283
DOI: 10.1002/jbmr.4647 -
Clinical Journal of the American... Dec 2019Erythropoiesis-stimulating agents correct anemia of CKD but may increase cardiovascular risk. We compared cardiovascular outcomes and all-cause mortality associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD: A Randomized Noninferiority Trial.
BACKGROUND AND OBJECTIVES
Erythropoiesis-stimulating agents correct anemia of CKD but may increase cardiovascular risk. We compared cardiovascular outcomes and all-cause mortality associated with monthly methoxy polyethylene glycol-epoetin beta with those of the shorter-acting agents epoetin alfa/beta and darbepoetin alfa in patients with anemia of CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a multicenter, open-label, noninferiority trial in which patients were randomized to receive methoxy polyethylene glycol-epoetin beta or reference erythropoiesis-stimulating agents, stratified by maintenance or correction treatment status and C-reactive protein level. The trial had a prespecified noninferiority margin of 1.20 for the hazard ratio (HR) for the primary end point (a composite of all-cause mortality, nonfatal myocardial infarction or stroke, adjudicated by an independent blinded committee). This trial is registered with ClinicalTrials.gov, number NCT00773513.
RESULTS
In total, 2818 patients underwent randomization, received methoxy polyethylene glycol-epoetin beta or a reference agent, and were followed for a median of 3.4 years (maximum, 8.4 years). In the modified intention-to-treat analysis, a primary end point event occurred in 640 (45.4%) patients in the methoxy polyethylene glycol-epoetin beta arm, and 644 (45.7%) in the reference arm (HR 1.03; 95% confidence interval [95% CI], 0.93 to 1.15, =0.004 for noninferiority). All-cause mortality was not different between treatment groups (HR 1.06; 95% CI, 0.94 to 1.19). Results in patient subgroups on dialysis or treated in the correction or maintenance settings were comparable to the primary analysis.
CONCLUSIONS
In patients with anemia of CKD, once-monthly methoxy polyethylene glycol-epoetin beta was noninferior to conventional, shorter-acting erythropoiesis-stimulating agents with respect to rates of major adverse cardiovascular events or all-cause mortality.
Topics: Aged; Anemia; Cardiovascular Diseases; Cause of Death; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Polyethylene Glycols; Renal Insufficiency, Chronic
PubMed: 31420350
DOI: 10.2215/CJN.01380219