Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.

BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.

Relationship of transcutaneous oxygen tension with age and skin elasticity in Korean women.

BACKGROUND: Oxygen has several positive effects on the skin, including improving collagen synthesis and accelerating wound healing. However, only a few studies have investigated the relationship between skin oxygenation and skin aging parameters. Therefore, this study aimed to assess the correlation between skin oxygenation and skin aging parameters-elasticity, hydration, sebum, color (lightness, redness), and blood perfusion-in Korean women. MATERIALS AND METHODS: We evaluated the transcutaneous partial pressure of oxygen, also known as transcutaneous oxygen tension (TcPO2 ), and skin aging parameters, including elasticity, hydration, sebum, color (lightness or redness), and blood perfusion, in the cheek of 34 healthy women (aged 20-69 years) and assessed the correlation between TcPO2 and other skin aging parameters using IBM SPSS Statistics 25 software (SPSS Inc). RESULTS: Facial TcPO2 was negatively correlated with age (P < .05). There were positive correlations between facial TcPO2 and elasticity parameters (P < .01). We noted no correlation between facial TcPO2 and skin lightness; however, skin lightness tended to slightly improve with increasing TcPO2 . Skin aging parameters, including hydration, sebum, skin redness, and blood perfusion, showed no correlations with TcPO2 . CONCLUSION: In Korean women, facial TcPO2 tends to decrease with increasing age and is positively correlated with gross, net, and biological skin elasticity. Therefore, this study demonstrated that oxygen tension of facial skin can be a major causative factor of skin aging.

Effects of levetiracetam monotherapy on the cognitive function of epilepsy patients.

AIMS: To estimate the effect of levetiracetam (LEV) on cognitive function and mood status in newly diagnosed epilepsy patients. METHODS: Fifty-five drug-naïve epilepsy patients (M:F ratio = 31:24; mean age = 30.9 years) were included. All patients underwent two neuropsychological (NP) tests, one before receiving LEV and then another 12.9 ± 5.0 months after starting LEV monotherapy. We evaluated general cognitive function, verbal/visual attention and memory, linguistic and visuospatial functions, frontal lobe function, and mood status. Repeated-measures regression and generalized estimating equation models were applied to assess the effects of all the confounding variables such as seizure control, average LEV dose, duration of epilepsy, inter-test interval, and subtype of epilepsy syndrome. RESULTS: LEV monotherapy over 1 year revealed significant improvements in the following domains of NP tests with the correction of possible confounding variables: verbal and visual attention, psychomotor speed, mental flexibility, executive function, verbal fluency and word generation. No NP domains showed any significant decrease. CONCLUSION: Our study suggested that LEV monotherapy had no harmful effect on cognitive function in drug-naïve patients with epilepsy.

Efficacy and Safety of Regdanvimab (CT-P59): A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial in Outpatients With Mild-to-Moderate Coronavirus Disease 2019.

Background: Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods: Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n = 100), regdanvimab 80 mg/kg (n = 103), or placebo (n = 104). The primary end points were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary end points included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results: Median (95% CI) time to negative conversion of RT-qPCR was 12.8 (9.0-12.9) days with regdanvimab 40 mg/kg, 11.9 (8.9-12.9) days with regdanvimab 80 mg/kg, and 12.9 (12.7-13.9) days with placebo. Median (95% CI) time to clinical recovery was 5.3 (4.0-6.8) days with regdanvimab 40 mg/kg, 6.2 (5.5-7.9) days with regdanvimab 80 mg/kg, and 8.8 (6.8-11.6) days with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6%-9.8%]) and regdanvimab 80 mg/kg (4.9% [2.1%-10.9%]) vs placebo (8.7% [4.6%-15.6%]). No serious treatment-emergent adverse events or deaths occurred. Conclusions: Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19. Clinical trial registration : NCT04602000 and EudraCT 2020-003369-20.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

[Observation on therapeutic effect of acupuncture at "experienced ten acupoints" for postprandial distress syndrome].

OBJECTIVE: To observe the clinical effect of acupuncture at "experienced ten acupoints" for postprandial distress syndrome. METHODS: A total of 62 patients with postprandial distress syndrome were randomly divided into an observation group (31 cases, 5 cases dropping off) and a control group (31 cases, 6 cases dropping off ). Acupuncture was applied at Baihui (GV 20), Zhongwan (CV 12), Qihai (CV 6), Tianshu (ST 25), Neiguan (PC 6), Zusanli (ST 36), Gongsun (SP 4), Danzhong (CV 17) in the observation group. In the control group, 6 non-acupoint points were intervened with shallow puncture. The treatment was given 20 min each time, once every other day, 3 times a week for a total of 4 weeks in the two groups. Symptom index of dyspepsia (SID) and Nepean dyspepsia index (NDI) scores were compared before and after treatment, and the efficacy was evaluated in the two groups. RESULTS: The effective rate in the observation group was 76.9% (20/26), which was higher than 28.0% in the control group (7/25, P<0.01). After treatment, the SID and NDI scores in the two groups were lower than those before treatment (P<0.01, P<0.05), and the SID and NDI scores in the observation group were lower than those in the control group (P<0.01, P<0.05). CONCLUSION: Acupuncture at "experienced ten acupoints" can significantly reduce the symptoms of dyspepsia and improve the quality of life in patients with postprandial distress syndrome.

Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia.

STUDY OBJECTIVE: To investigate the structural changes in patients with chronic primary insomnia and the relationships with clinical features of insomnia. DESIGN: Statistical parametric mapping 8-based voxel-based morphometry was used to identify differences in regional gray and white matter between patients with chronic primary insomnia and normal controls. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Twenty-seven patients and 27 age/sex-matched controls. INTERVENTIONS: Regional differences were compared using two-sample t-tests with age, sex, and intracranial volume as covariates. MEASUREMENTS AND RESULTS: The patients were a mean age of 52.3 y and had a mean history of insomnia of 7.6 y. Patients displayed cognitive deficits in attention, frontal/executive function, and nonverbal memory. Patients also displayed significantly reduced gray matter concentrations (GMCs) in dorsolateral prefrontal and pericentral cortices, superior temporal gyrus, and cerebellum and decreased gray matter volumes in medial frontal and middle temporal gyri compared with control patients with the cluster threshold ≥ 50 voxels at the level of uncorrected P < 0.001. Negative correlations were found between GMC of the prefrontal cortex and insomnia severity and the wakefulness after sleep onset, and between GMC of pericentral cortex and sleep latencies. None of the findings continued to be significant after correction for multiple comparisons. CONCLUSIONS: We found gray matter deficits in multiple brain regions including bilateral frontal lobes in patients with psychophysiologic insomnia. Gray matter deficit of the pericentral and lateral temporal areas may be associated with the difficulties in sleep initiation and maintenance. It is still unclear whether gray matter reductions are a preexisting abnormality or a consequence of insomnia. CITATION: Joo EY; Noh HJ; Kim JS; Koo DL; Kim D; Hwang KJ; Kim JY; Kim ST; Kim MR; Hong SB. Brain gray matter deficits in patients with chronic primary insomnia. SLEEP 2013;36(7):999-1007.