scholarly journals Efficacy of tiotropium and olodaterol combination therapy on dynamic lung hyperinflation evaluated by hyperventilation in COPD: an open-label, comparative before and after treatment study

2019 ◽  
Vol Volume 14 ◽  
pp. 1167-1176 ◽  
Author(s):  
Shohei Kawachi ◽  
Keisaku Fujimoto
Keyword(s):  
Combination Therapy ◽  
Open Label ◽  
Lung Hyperinflation ◽  
Before And After ◽  
Dynamic Lung Hyperinflation

Influence of lung Hyperinflation on Respiratory Muscles Pressures During a Submaximal test in Patients with COPD: a Clinical Perspective

2020 ◽  
Vol 16 ◽  
Author(s):  
Elias Ferreira Porto ◽  
Sabrina Clares ◽  
Ana Maria Jora Ferracioli ◽  
Marcio Ricardo Pereira de Sousa ◽  
José Renato de Oliveira Leite ◽  
...  
Keyword(s):  
Respiratory Muscles ◽  
Diaphragm Muscle ◽  
Dynamic Hyperinflation ◽  
Expiratory Flow Limitation ◽  
Walking Test ◽  
Lung Hyperinflation ◽  
Submaximal Exercise Test ◽  
Copd Patients ◽  
Before And After ◽  
Dynamic Lung Hyperinflation

Background and objective:: Reduction of exercise tolerance is associated with expiratory flow-limitation (EFL) and lung hyperinflation; those are only partially reversible to bronchodilator. Lung hyperinflation lowers the diaphragm muscle provoking a mechanical disadvantage that, eventually, reduces maximal inspiratory (MIP) and expiratory (MEP) pressures. We aimed to assess the influence of the dynamic lung hyperinflation on respiratory pressures changes at rest and after a submaximal exercise test in COPD patients with and without bronchodilator. Methods:: We prospectively analyzed 16 COPD patients (FEV1 36.4±10% pred.; age 61.0±8 years, height 165±12 cm and BMI 25.9±6 kg/m2). MIP and MEP were measured before and after performing the six minutes walking test (6MWT) with and without bronchodilator (400 mcg of albuterol). Results:: Nine of 16 patients increased IC more than 150 ml after bronchodilator use. Right after the 6MWT accomplished without bronchodilator IC decreased 7.05% compared to the 6MWT baseline value (p<0.01). Nine patients decreased IC more than 150ml. After bronchodilator use patients performed the 6MWT without any IC significant reduction (p>0.05). Twelve patients increased the MIP (ranging from 70±11cmH2O to 77±10cmH2O, p = 0.0043) using 400mcg of albuterol. Thirteen patients reduced MIP after the 6MWT without bronchodilator use (p <0.007). There was no significant reduction (p> 0.05) in MIP when patients performed the 6MWT after bronchodilator use. We also found a significant correlation between MIP and inspiratory capacity (IC) and MEP and the IC before and after the 6MWT (r=0.61, p=0.0054; r=0.60, p=0.0031, respectively). Conclusions:: Dynamic pulmonary hyperinflation directly interferes with the ability of respiratory muscles to generate inspiratory and expiratory pressures. The previous use of bronchodilator in patients with COPD reduced dynamic hyperinflation when accomplishing a sub-maximal exercise.

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

scholarly journals MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors

2021 ◽  
Author(s):  
Ying Meng ◽  
Christopher B Pople ◽  
Suganth Suppiah ◽  
Maheleth Llinas ◽  
Yuexi Huang ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Specific Protein ◽  
Rank Test ◽  
Open Label ◽  
Isocitrate Dehydrogenase 1 ◽  
Serious Adverse Events ◽  
Before And After ◽  
Bbb Opening

Abstract Background Liquid biopsy is promising for early detection, monitoring of response and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy. Methods Nine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening alone (NCT03739905). Results Brain regions averaging 7.8±6.0 cm 3 (range 0.8–23.1 cm 3) were successful treated within 111±39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6±1.2 fold, p&lt;0.01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2±1.9 fold, p&lt;0.01), and brain specific protein S100b (1.4±0.2 fold, p&lt;0.01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease and post-BBB opening specific, in keeping with our hypothesis. We also found cfDNA mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbour the tumor mutation. Conclusions This first-in-human proof-of concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.

scholarly journals LGG-49. SAFETY AND EFFICACY OF TRAMETINIB (T) MONOTHERAPY AND DABRAFENIB + TRAMETINIB (D+T) COMBINATION THERAPY IN PEDIATRIC PATIENTS WITH BRAF V600-MUTANT LOW-GRADE GLIOMA (LGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii375-iii375
Author(s):  
Eric Bouffet ◽  
James A Whitlock ◽  
Christopher Moertel ◽  
Birgit Geoerger ◽  
Isabelle Aerts ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Pediatric Patients ◽  
Objective Response ◽  
Safety Data ◽  
Dose Finding ◽  
Combination Group ◽  
Clinical Activity ◽  
Low Grade ◽  
Open Label ◽  
Independent Review

Abstract BACKGROUND Children with BRAF V600-mutant LGG have suboptimal response to standard chemotherapy. Previously, D (BRAF V600 inhibitor) monotherapy has demonstrated clinical benefit in this population. We report interim analysis results of pediatric patients with recurrent/refractory BRAF V600-mutant LGG treated with either T (MEK1/2 inhibitor) monotherapy or D+T combination therapy. METHODS This is a 4-part, open-label, multicenter, phase I/II study (NCT02124772) in pediatric patients (&lt;18 y) with refractory/recurrent tumors. The dose-finding phase, including dose confirmation stratified by age, was followed by disease-specific cohorts at recommended dose levels. Efficacy was determined by both investigator and independent review using RANO criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03. RESULTS Of 49 pediatric patients with BRAF V600-mutant LGG (T, n=13; D+T, n=36) enrolled, pooled efficacy data was available for both treatments while safety data was available for 30 patients (T, n=10; D+T, n=20). Most patients (n=8/10) receiving T monotherapy withdrew/discontinued the treatment in contrast to 3/20 in the D+T group. Pyrexia occurred in 50% of patients (n=5/10) in the monotherapy group and was a frequent AE in the combination group (75%; n=15/20). Objective response rate per independent review was 15% (95% CI, 2%–45%) with T monotherapy and 25% (95% CI, 12%–42%) with D+T combination therapy. Seven patients (54%) on monotherapy and 33 patients (92%) on combination therapy had stable disease or better. CONCLUSION In pediatric patients with previously treated BRAF V600-mutant LGG, T monotherapy and D+T combination therapy demonstrated clinical activity, with pyrexia being a common AE.

scholarly journals An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Roger Hesselstrand ◽  
Jörg H. W. Distler ◽  
Gabriela Riemekasten ◽  
Dirk M. Wuttge ◽  
Marie Törngren ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Type I ◽  
Type I Ifn ◽  
Open Label ◽  
Reactive Protein ◽  
Before And After ◽  
Modified Rodnan Skin Score ◽  
Skin Biopsies ◽  
Rank 2

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

scholarly journals Are Three Weeks of Oral Anticoagulation Sufficient for Safe Cardioversion in Atrial Fibrillation?

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 554
Author(s):  
Stefan Naydenov ◽  
Nikolay Runev ◽  
Emil Manov
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Left Atrial Volume ◽  
Open Label ◽  
Before And After ◽  
Individualized Approach ◽  
Baseline Factors ◽  
And Function

Background and Objectives: Patients with atrial fibrillation (AF), lasting >48 h, considered for cardioversion, are recommended ≥3 weeks of oral anticoagulation before sinus rhythm restoration because of high risk of development of left atrial thrombosis (LAT) and stroke. However, the optimal duration of anticoagulation in the presence of overt LAT is unknown. Materials and Methods: An open-label study aimed to investigate the prevalence of spontaneous echo contrast (SEC) and LAT before and after 3 weeks of direct oral anticoagulant (DOAC) treatment. We included 51 consecutive patients (50.9% males), mean age 69.3 ± 7.4 years with paroxysmal/unknown duration of AF, considered for cardioversion, who agreed to have transesophageal echocardiography at enrollment and 3 weeks later. Results: At baseline SEC was present in 26 (50.9%) and LAT in 10 (19.6%) of 51 patients. After 3 weeks on DOAC, SEC persisted in 12 (25.0%) and LAT in 7 (14.5%) of 48 patients, p < 0.05 vs. baseline. Factors, associated most strongly with persistence of SEC/LAT, were left atrial appendage (LAA) emptying velocity <20 cm/s (OR = 2.82), LAA lobes >2 (OR = 1.84), and indexed left atrial volume ≥34 mL/m2 (OR = 1.37). Conclusions: In our study the incidence of SEC/LAT, particularly in AF with unknown duration, was not as low as we expected. The prevalence of SEC/LAT seemed to be dependent on factors not routinely evaluated in AF patients planned for cardioversion (indexed LA volume, LAA morphology and number of lobules, LAA emptying velocity, etc.). Our data suggested an individualized approach for DOAC duration in AF patients before an attempt for restoration of sinus rhythm is made, taking into consideration the LAA morphology and function.

scholarly journals Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses

2021 ◽  
Vol 11 (4) ◽  
pp. 508
Author(s):  
Michael Schaefer ◽  
Julian Hellmann-Regen ◽  
Sören Enge
Keyword(s):  
Stress Responses ◽  
Acute Stress ◽  
Stress Test ◽  
Self Report ◽  
Control Group ◽  
Relaxation Techniques ◽  
Open Label ◽  
Before And After ◽  
Cortisol Responses ◽  
Negative Feelings

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.

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