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OBJECTIVES: Although guidelines recommend antiviral therapy for outpatients with COVID-19 who are at high risk of progressing to severe conditions, such as older adults, many patients do not receive appropriate treatment. Little is known, however, about the physician factors associated with the prescription of guideline-recommended antiviral therapy for patients with COVID-19. DESIGN: A cross-sectional study. SETTING: Data including outpatient visits in primary care clinics in Japan from April to August 2023. PARTICIPANTS: We analysed 30 953 outpatients aged ≥65 years treated with COVID-19 (mean (SD) age, 75.0 (7.6) years; 17 652 women (57.0%)) in 1394 primary care clinics. OUTCOME MEASURES: The primary outcome was the prescription of guideline-recommended antivirals (ie, nirmatrelvir-ritonavir or molnupiravir), adjusted for patient characteristics, months of visits and regions. RESULTS: Antiviral prescriptions were concentrated among a small proportion of physicians; for example, the top 10% of physicians that had the largest number of nirmatrelvir-ritonavir prescriptions accounted for 92.4% of all nirmatrelvir-ritonavir prescriptions. After adjusting for potential confounders, physicians with higher patient volumes were more likely to prescribe guideline-recommended antivirals to their patients (adjusted OR (aOR) for high vs low volume, 1.76; 95% CI 1.31 to 2.38; adjusted p<0.001). We found no evidence that the likelihood of guideline-recommended antiviral prescription differed based on physicians' gender (aOR for women vs men, 1.24; 95% CI 0.88 to 1.74; adjusted p=0.48) or age (aOR for 45-59 vs <45 years, 1.16; 95% CI 0.87 to 1.54; adjusted p=0.48; aOR for ≥60 vs <45 years, 0.88; 95% CI 0.66 to 1.16; adjusted p=0.48). These patterns were similar when examining nirmatrelvir-ritonavir and molnupiravir separately. CONCLUSIONS: Our findings suggest that provider-level factors, such as the clinical experience of treating the patients with COVID-19, play an important role in the appropriate prescription of antiviral medications for COVID-19 in the primary care setting.
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COVID-19 , Citidina/análogos & derivados , Hidroxilaminas , Lactamas , Leucina , Nitrilos , Prolina , Masculino , Humanos , Femenino , Anciano , Japón/epidemiología , Estudios Transversales , Ritonavir/uso terapéutico , Antivirales/uso terapéuticoRESUMEN
This cross-sectional study assesses the characteristics of patients and physicians associated with antibiotic prescription for COVID-19.
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COVID-19 , Pacientes Ambulatorios , Humanos , Japón , Atención Primaria de SaludRESUMEN
For plasma spectroscopy, Stokes spectropolarimetry is used as a method to spatially invert the viewing-chord-integrated spectrum on the basis of the correspondence between the given magnetic field profile along the viewing chord and the Zeeman effect appearing on the spectrum. Its application to fusion-related toroidal plasmas is, however, limited owing to the low spatial resolution as a result of the difficulty in distinguishing between the Zeeman and Doppler effects. To resolve this issue, we increased the relative magnitude of the Zeeman effect by observing a near-infrared emission line on the basis of the greater wavelength dependence of the Zeeman effect than of the Doppler effect. By utilizing the increased Zeeman effect, we are able to invert the measured spectrum with a high spatial resolution by Monte Carlo particle transport simulation and by reproducing the measured spectra with the semiempirical adjustment of the recycling condition at the first walls. The inversion result revealed that when the momentum exchange collisions of atoms are negligible, the velocity distribution of core-fueling atoms is mainly determined by the initial distribution at the time of recycling. The inversion result was compared with that obtained using a two-point emission model used in previous studies. The latter approximately reflects the parameters of atoms near the emissivity peak.
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PURPOSE: To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). STUDY DESIGN: Open-label, multicenter, Phase 3 study (NCT02822729). METHODS: Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16- < 22 mmHg (Group 1) or ≥ 22- ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients (N = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. RESULTS: Significant reductions in mean diurnal IOP from baseline occurred at every visit (P < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was -3.7 ± 0.3 mmHg (Group 1), -5.6 ± 0.5 mmHg (Group 2), and -8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. CONCLUSIONS: In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia.
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Glaucoma de Ángulo Abierto , Hipertensión Ocular , Antihipertensivos/efectos adversos , Método Doble Ciego , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glicina/análogos & derivados , Humanos , Presión Intraocular , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Pirazoles , Piridinas , Timolol/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the efficacy and safety of omidenepag isopropyl (OMDI), a selective, non-prostaglandin, prostanoid EP2 receptor agonist, in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). DESIGN: Phase III, randomized, investigator-masked, active-controlled, parallel-group, noninferiority study (ClinicalTrials.govNCT02623738). METHODS: After a washout period of 1-4 weeks, eligible patients were randomized (1:1) to OMDI 0.002% or latanoprost 0.005% once daily for 4 weeks. Intraocular pressure (IOP) was measured at 9:00 AM, 1:00 PM, and 5:00 PM at weeks 1, 2, and 4. The primary endpoint was the change from baseline in mean diurnal IOP at week 4. The noninferiority margin for OMDI versus latanoprost was 1.5 mm Hg. Adverse events (AEs) were recorded. RESULTS: Of the 190 patients randomized, 189 had at least 1 post-baseline IOP measurement. At baseline, patients who received OMDI or latanoprost had a mean ± SD diurnal IOP of 23.78 ± 1.73 mm Hg and 23.40 ± 1.51 mm Hg, respectively. At week 4, least-squares mean ± SE reduction in IOP from baseline with OMDI (-5.93 ± 0.23 mm Hg) was noninferior to that of latanoprost (-6.56 ± 0.22 mm Hg; 95% confidence interval between groups: 0.01-1.26). The most frequently reported treatment-related ocular AEs (OMDI vs latanoprost) were conjunctival hyperemia (23/94 patients [24.5%] vs 10/96 patients [10.4%]), corneal thickening (11/94 patients [11.7%] vs 1/96 patients [1.0%]), and punctate keratitis (0/94 patients vs 5/96 patients [5.2%]). No serious AEs were observed in either group, and there were no discontinuations related to the study drug. CONCLUSIONS: OMDI 0.002% was noninferior to latanoprost 0.005% in reducing IOP in patients with OHT or POAG and was well tolerated.
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Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glicina/análogos & derivados , Presión Intraocular/efectos de los fármacos , Latanoprost/administración & dosificación , Hipertensión Ocular/tratamiento farmacológico , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Glicina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/fisiopatología , Soluciones Oftálmicas/administración & dosificación , Método Simple Ciego , Resultado del TratamientoRESUMEN
PURPOSE: Omidenepag isopropyl (OMDI) is the prodrug of omidenepag, a selective, non-prostaglandin, prostanoid EP2 receptor agonist, which has been shown to lower intraocular pressure (IOP) in patients with glaucoma and ocular hypertension (OHT). This study evaluated the efficacy and safety of OMDI ophthalmic solution 0.002% in patients with primary open-angle glaucoma or OHT who were non-/low responders to latanoprost. STUDY DESIGN: Open-label, multicenter, Phase 3 study (NCT02822742). METHODS: Following 1-4-week washout, patients were treated with latanoprost ophthalmic solution 0.005% during an 8-week run-in period. Patients with ≤15% IOP reduction at the end of the run-in (indicating non-/low response) received OMDI 0.002% (one drop once daily for 4 weeks). The primary endpoint was the change from baseline in mean diurnal IOP at Week 4. RESULTS: In total, 26 patients were treated with OMDI; two withdrew owing to lack of efficacy. The mean diurnal IOP at baseline (end of latanoprost run-in) was 23.1 mmHg (7.6% IOP reduction from end of washout) indicating non-/low response to latanoprost. After 4 weeks of OMDI treatment, mean diurnal IOP was significantly reduced from baseline (-2.99 mmHg; P < 0.0001). No serious adverse events were reported. Adverse events occurred in five patients (19.2%); adverse drug reactions (anterior chamber cell, conjunctival hyperemia, and erythema of eyelid) occurred in two patients (7.7%) and were mild in severity. CONCLUSIONS: In this study, OMDI 0.002% demonstrated a clinically significant reduction in IOP and was well tolerated in patients with primary open-angle glaucoma and OHT who were non-/low responders to latanoprost.
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Antihipertensivos/uso terapéutico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glicina/análogos & derivados , Presión Intraocular/efectos de los fármacos , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Subtipo EP2 de Receptores de Prostaglandina E/agonistas , Administración Oftálmica , Anciano , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Glicina/uso terapéutico , Humanos , Presión Intraocular/fisiología , Latanoprost/uso terapéutico , Masculino , Persona de Mediana Edad , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Soluciones Oftálmicas , Microscopía con Lámpara de Hendidura , Tonometría Ocular , Resultado del TratamientoRESUMEN
PRéCIS:: Three randomized, multicenter studies demonstrated the stable intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in patients with primary open-angle glaucoma and ocular hypertension; 0.002% was identified as the optimal dose for further investigation. PURPOSE: The purpose of this study was to assess the safety and efficacy of omidenepag isopropyl, a selective EP2 agonist, and to determine the optimal dose for further investigation. PATIENTS AND METHODS: Three randomized, controlled, masked, multicenter studies were conducted in United States (study 1, NCT01868126; study 2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the observed mean diurnal intraocular pressure (IOP) and IOP at each time point on the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at week 4 (study 3). RESULTS: IOP-lowering effects of omidenepag isopropyl 0.0003% to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% resulted in clinically relevant mean diurnal IOP reductions from baseline that were similar to those of latanoprost and superior to placebo (P<0.005). Maximum reductions had already been achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months. Most adverse events (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the incidence of which increased dose-dependently. The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs in the 0.002% group. CONCLUSIONS: Omidenepag isopropyl demonstrated stable IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal dose for phase 3 investigation.
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Antihipertensivos/administración & dosificación , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glicina/análogos & derivados , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Subtipo EP2 de Receptores de Prostaglandina E/agonistas , Anciano , Paquimetría Corneal , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Glicina/administración & dosificación , Humanos , Presión Intraocular/efectos de los fármacos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Oftalmoscopía , Microscopía con Lámpara de Hendidura , Tonometría OcularRESUMEN
PURPOSE: We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. PATIENTS AND METHODS: A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. RESULTS: According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. CONCLUSION: The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye.