scholarly journals Enhanced airway sensory nerve reactivity in non-eosinophilic asthma

2021 ◽  
Vol 8 (1) ◽  
pp. e000974
Author(s):  
Hajar Ali ◽  
Collin Brooks ◽  
Julian Crane ◽  
Richard Beasley ◽  
Stephen Holgate ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Geometric Mean ◽  
Sensory Nerve ◽  
Airway Hyperreactivity ◽  
Neural Mechanisms ◽  
Sputum Induction ◽  
Eosinophilic Asthma ◽  
Sputum Eosinophils ◽  
The Difference ◽  
Blood Eosinophils

BackgroundNeural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.MethodsThirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.ResultsNon-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed.ConclusionNEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.

scholarly journals Enhanced sensory nerve reactivity in non-eosinophilic asthma

2021 ◽  
Author(s):  
Hajar Ali ◽  
Collin Brooks ◽  
Julian Crane ◽  
Richard Beasley ◽  
Stephen Holgate ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Sensory Nerve ◽  
Airway Hyperreactivity ◽  
Neural Mechanisms ◽  
Sputum Eosinophil ◽  
Sputum Induction ◽  
Eosinophilic Asthma ◽  
Significant Difference ◽  
Sputum Eosinophils ◽  
Blood Eosinophils

ABSTRACT Background: Neural mechanisms may play an important role in non-eosinophilic asthma. This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic and non-eosinophilic asthma and non-asthmatics. Methods: Thirty-eight asthmatics and nineteen non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), atopy, and spirometry tests, followed by capsaicin challenge. Eosinophilic (EA) and non-eosinophilic asthma (NEA) were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity (AHR) was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. Results: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared to non-asthmatics (n=19) (geometric mean C5: 58.3μM, 95% confidence interval 24.1-141.5 vs 193.6μM, 82.2-456.0; p<0.05). There was a similar (but non-significant) difference in capsaicin sensitivity in NEA compared with EA (n=18), (58.3μM, 24.1-141.5 vs 191.0μM, 70.9-514.0; p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control, or treatment were observed. Conclusion: Non-eosinophilic asthma, but not eosinophilic asthma, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of non-eosinophilic asthma.

scholarly journals Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: A randomized, placebo controlled trial

1998 ◽  
Vol 5 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Mark O Turner ◽  
Patrick R Johnston ◽  
Emilio Pizzichini ◽  
Marcia MM Pizzichini ◽  
Pat A Hussack ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Geometric Mean ◽  
Beta Agonist ◽  
Airflow Limitation ◽  
Clinical Test ◽  
Clinical Parameters ◽  
Sputum Eosinophils ◽  
Anti Inflammatory ◽  
Long Acting ◽  
Blood Eosinophils

BACKGROUND: Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma.OBJECTIVE: To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property.PATIENTS AND METHODS: Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 µg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 µg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis.RESULTS: Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters.CONCLUSIONS: These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist.

COMPARATIVE EVALUATION OF MULTIPARAMETRIC ENDORECTAL ULTRASOUND AND ENHANCED IMAGING COLONOSCOPY IN THE DIAGNOSIS OF EARLY COLORECTAL CANCER

2020 ◽  
Vol 19 (3) ◽  
pp. 49-64
Author(s):  
E. M. Bogdanova ◽  
Yu. L. Trubacheva ◽  
O. M. Yugai ◽  
S. V. Chernyshov ◽  
E. G. Rybakov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Statistical Significance ◽  
Muscle Layer ◽  
Endorectal Ultrasound ◽  
Diagnostic Methods ◽  
Early Colorectal Cancer ◽  
Morphological Examination ◽  
Optical Magnification ◽  
The Difference ◽  
Enhanced Imaging

AIM: to compare multiparametric endorectal ultrasound (ERUS) and enhanced imaging colonoscopy in the diagnosis of early colorectal cancer.PATIENTS AND METHODS: the study included 78 patients with epithelial rectal tumor. All the patients underwent multiparametric ERUS and colonoscopy with examination by narrow beam imaging (NBI) at optical magnification. All the patients were operated.RESULTS: a morphological examination removed specimens revealed adenomas in 48 cases, in 19 specimens – adenocarcinomas in situ and T1, and in 11 specimens – adenocarcinomas with invasion of the muscle layer or deeper. When calculating the accuracy indicators of diagnostic methods for groups of patients with adenoma, Tis-T1 adenocarcinoma, and T2-T3 adenocarcinoma, the difference in the sensitivity and specificity of the methods in none of the presented groups did not reach the level of statistical significance (p>0.05).ROC analysis showed that ultrasound has a prognostic value comparable to colonoscopy. The area difference was 0.013 (p=0.85).CONCLUSION: endoscopy and ultrasound have similar value in the diagnosis of malignant transformation of rectal adenomas.

Clinical Study of Qingpeng Ointment Treatment of Shoulder-Hand Syndrome After Cerebral Hemorrhage During the Rehabilitation Period

2020 ◽  
Vol 23 ◽  
Author(s):  
Ruihuan Pan ◽  
Shanshan Ling ◽  
Haodong Yang ◽  
Yan Huang ◽  
Lechang Zhan ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cerebral Hemorrhage ◽  
Clinical Medicine ◽  
External Rotation ◽  
Statistical Significance ◽  
Hand Function ◽  
Tibetan Medicine ◽  
Controlled Study ◽  
Control Group ◽  
The Difference

Background: Shoulder-hand syndrome (SHS) refers to a syndrome causing sudden edema, shoulder pain and limited hand function. Qingpeng ointment, a kind of Tibetan medicine, can reduce swelling, relieve pain, tonify stagnation and clear the meridians, which is consistent with the pathological mechanism of SHS after stroke. Therefore, if clinical trials can be used to explore the effectiveness of Qingpeng ointment for treatment of poststroke SHS and promote its application in clinical medicine, this is of specific significance for the treatment of poststroke SHS. Objective: To investigate the clinical efficacy and safety of Qingpeng ointment in the treatment of poststroke SHS. To provide an objective basis for a better therapeutic treatment for poststroke SHS． Method: A prospective, randomized, controlled study was conducted. This study recruited 120 patients with poststroke SHS who met the inclusion criteria. They were randomized into the treatment group and the control group, with 60 patients allocated to each group. The treatment group received routine medical treatment and rehabilitative care after using the Qingpeng ointment, while the patients in the control group received only routine treatment without the ointment. All patients received clinical assessment with the Visual Analogue Scale (VAS), measurement of the range of motion (ROM) of the upper-limb joints, the Fugl-Meyer Assessment of Upper Extremity (FMA-U) and the Modified Barthel Index Score (MBI) before and after the whole treatment. Results: After 4 weeks of treatment, the VAS scores of both groups were decreased significantly (P＜0.05), and the difference between the two groups was statistically significant (P < 0.05). There is no statistical significance for the difference between the treatment group and control group in terms of the FMA-U and MBI scores and the forward bend, backward, outstretch, external rotation and pronation angles after treatment. The increases in the values of VAS, FMA-M and MBI in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). The increases in the values of the forward bend, outreach and external rotation angles in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). Conclusion: The treatment group showed better results than the control group in terms of the relief of pain symptoms, the improvement of motor function and the improvement of the activities of daily living for patients with shoulder-hand syndrome after cerebral hemorrhage. Qingpeng ointment is effective and safe in treating poststroke SHS.

scholarly journals Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

2020 ◽  
Author(s):  
Elena V Esaulenko ◽  
Aleksey A Yakovlev ◽  
Genady A Volkov ◽  
Anastasia A Sukhoruk ◽  
Kirill G Surkov ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Geometric Mean ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Antigen Vaccine ◽  
Single Antigen ◽  
Antibody Titers ◽  
The Russian Federation ◽  
The Difference ◽  
Mean Concentration

Abstract Background This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. Methods We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: &gt; − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). Results Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was &gt;97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

scholarly journals Reporting stAndards for research in PedIatric Dentistry (RAPID): an expert consensus-based statement

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jayakumar Jayaraman ◽  
Vineet Dhar ◽  
Kevin J. Donly ◽  
Ekta Priya ◽  
Daniela P. Raggio ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Pediatric Dentistry ◽  
Reporting Guidelines ◽  
Expert Consensus ◽  
Reporting Standards ◽  
Weighted Mean ◽  
Care Needs ◽  
Research Reporting ◽  
The Difference ◽  
Executive Group

Abstract Background Reporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process. Methods The development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes. Results The final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05). Conclusions The RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported.

scholarly journals Cyclic fatigue resistance of 2Shape, Twisted File and EndoSequence Xpress nickel-titanium rotary files at intracanal temperature

2018 ◽  
Vol 12 (4) ◽  
pp. 283-287 ◽  
Author(s):  
Gülşah Uslu ◽  
Taha Özyürek ◽  
Mustafa Gündoğar ◽  
Koray Yılmaz
Keyword(s):  
Fatigue Resistance ◽  
Statistical Significance ◽  
Cyclic Fatigue ◽  
Nickel Titanium ◽  
Bonferroni Correction ◽  
Significant Difference ◽  
Inner Diameter ◽  
The Difference ◽  
Number Of Cycles ◽  
Analyze Data

Background. The aim of this study was to compare the cyclic fatigue resistance of 2Shape, Twisted File (TF) and EndoSequence Xpress (ESX) nickel-titanium rotary files at intracanal temperature (35°C). Methods. Twenty 2Shape TS1 (25/.04), 20 TF (25/.04) and 20 ESX (25/.04) files were tested for cyclic fatigue at intracanal temperature (35°C). All the instruments were rotated in artificial canals which were made of stainless steel with an inner diameter of 1.5 mm, 60° angle of curvature and a radius curvature of 5 mm until fracture occurred; the time to fracture was recorded in seconds using a digital chronometer and the number of cycles to fracture (NCF) for each file was calculated. Kruskal-Wallis test with Bonferroni correction was performed to statistically analyze data using SPSS 21.0. Statistical significance was set at P<0.05. Results. NCF values revealed that the 2Shape had significantly the highest cyclic fatigue resistance, followed by TF and ESX at intracanal temperature (P<0.05). The difference was significant between the TF and ESX groups (P<0.05). There was no significant difference among the 2Shape, TF and ESX files with respect to the lengths of the fractured file fragments (P>.05). Conclusion. Within the limitations of present study, it was concluded that the cyclic fatigue resistance of 2Shape files at the intracanal temperature is higher than that of TF and ESX files.

Neurovascular changes after four-layer compression bandaging in people with chronic venous leg ulcers

2007 ◽  
Vol 22 (2) ◽  
pp. 49-55 ◽  
Author(s):  
R Ogrin ◽  
P Darzins ◽  
Z Khalil
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Statistical Significance ◽  
Sensory Nerve ◽  
Compression Therapy ◽  
Clinical Problem ◽  
Leg Ulcers ◽  
Venous Leg Ulcers ◽  
Perfusion Measurement ◽  
Compression Bandaging

Objectives: Venous leg ulcers represent a major clinical problem, with poor rates of healing. Ideal treatment is compression bandaging. The effect of compression on neurovascular tissues involved in wound repair is unclear. This study aims to assess the effect of four-layer compression therapy (40 mmHg) on neurovascular function and wound healing in people with chronic venous leg ulcers – 15 people (55 years or older) with venous leg ulcers for more than six weeks. Methods: Basal microvascular perfusion measurement (MPM), oxygen tension (tc pO2) measured at sensor temperatures of 39°C and 44°C and sensory nerve function using electrical cutaneous perception thresholds (ECPT) at 5, 250 and 2000 Hz (corresponding to C, A δ and A β fibres) were assessed adjacent to the ulcer site, and at a mirror location on the non-ulcerated limb. Testing was undertaken before and after therapy for 5–12 weeks of four-layer compression bandaging. Results: There was significant improvement in tc pO2 at 44°C and ECPT at 2000 Hz ( P<0.05) compared with pre-intervention. Changes in basal MPM, tc pO2 at 39°C and ECPT at 5 and 250 Hz after compression therapy did not reach statistical significance. Conclusion: Four-layer compression bandaging in people with venous leg ulcers improved some components of neurovascularture in people with chronic venous leg ulcers. Whether this improvement has contributed to wound healing in this study requires further investigation.

Dichotomization, Partial Correlation, and Conditional Independence

1996 ◽  
Vol 21 (3) ◽  
pp. 264-282 ◽  
Author(s):  
András Vargha ◽  
Tamás Rudas ◽  
Harold D. Delaney ◽  
Scott E. Maxwell
Keyword(s):  
Conditional Independence ◽  
Partial Correlation ◽  
Statistical Significance ◽  
Conventional Wisdom ◽  
Predictor Variables ◽  
Lower Power ◽  
Partial Correlations ◽  
Current Article ◽  
The Difference ◽  
The Relationship

It was recently demonstrated that performing median splits on both of two predictor variables could sometimes result in spurious statistical significance instead of lower power. Not only is the conventional wisdom that dichotomization always lowers power incorrect, but the current article further demonstrates that inflation of apparent effects can also occur in certain cases where only one of two predictor variables is dichotomized. In addition, we show that previously published formulas claiming that correlations are necessarily reduced by bivariate dichotomization are incorrect. While the magnitude of the difference between the correct and incorrect formulas is not great for small or moderate correlations, it is important to correct the misunderstanding of partial correlations that led to the error in the previous derivations. This is done by considering the relationship between partial correlation and conditional independence in the context of dichotomized predictor variables.

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