LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis.

BACKGROUND: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting ß2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. METHODS: We searched several databases and manufacturers' websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. RESULTS: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79-1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90-1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81-1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86-1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52-64 weeks). CONCLUSION: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

Base on concept of traditional Chinese medicine: Experimental studies on efficacy of BIOCERAMIC Resonance to alleviate drug withdrawal symptoms.

Those who are challenged by dependency on prescription drugs or suffer drug addictions have few options available to them for recovery, such as psychotherapy and physiotherapy. Here we present a new approach with clinical examples involving stimulant addiction or overdose of hypnotic drugs that were received BIOCERAMIC Resonance, which was developed based on concept of 12 meridian channels of traditional Chinese medicine, and has successful withdrawal or dose reduction benefits. We describe the whole process and the clinical outcome. And by help of our previous publication on functional MRI, we discuss the possible brain locations response to BIOCERAMIC Resonance that may be corresponding to the beneficial effects of relief of depression, sleep deprivation and other mental symptoms that associate with substance abuse and withdrawal effects. We suggest this could be potentially widely application on substances abuse.

Whole genome gene expression changes and hematological effects of rikkunshito in patients with advanced non-small cell lung cancer receiving first line chemotherapy.

It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09-1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24.

Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: A systematic review and meta-analysis of randomized controlled trials.

Several long-acting bronchodilators have been developed and are widely used as first-line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers' websites to identify relevant randomized clinical trials for meta-analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1 ), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74-0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86-0.97, P = 0.005). There were no significant differences in trough FEV1 , TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.

Evaluation of Reflexology by "BIOCERAMIC Resonance" Operation producing Weak Force Field during Simultaneous Acupoint Stimulation of Urinary Bladder Point on Subject's Ear Resulting in Electric Current Change on Urinary Bladder reflex Point on Subject's Hands, and Related New Research Finding.

OBJECTIVE: It was postulated in our previous publications that the meridian channels as conceived in Traditional Chinese Medicine (TCM) are various standing waves arising from harmonic rhythmic sound frequencies originating from the human heart beat. BIOCERAMIC is an artificial material able to produce a weak force field causing different biophysical and systemic health benefits, with the key characteristics of hydrogen bonds weakening and microcirculation enhancement. Since discovering that the effects of a BIOCERAMIC field can be transmitted via sound waves propagation, we then also developed a BIOCERAMIC Resonance device to produce weak force field throughout the body, and achieve resonance with the body's meridian channels to reinforce microcirculation. METHODS: Since our previous research proved BIOCERAMIC can produces changes in ectodermal current levels, the present evaluation on reflexology is done by the application of Electric Current Detection (ECD) to the palmar surface of the hands matching correlative organs and glands loci to reflex points according to standard reflexology. The procedure will compare changes in the electrical current observed before and after a session of BIOCERAMIC Resonance treatment on the soles of the subjects' feet. We also conducted a procedure using corona discharge (Kirlian) photography of the hands to examine whether the coronal intensities could be affected by application of the BIOCERAMIC patch. Intensities are shown on the screen of a computer using special software that categorizes intensities into five zones. RESULTS: Under the continuous treatment of BIOCERAMIC Resonance on soles of the feet and simultaneous stimulation on the specific point on the surface of the ear representing the urinary bladder. The electrical current (Aji ampere) on the areas in the hands are decreased from the beginning of the experiment, but only the specific area on the surface of the ear representing the urinary bladder was exhibited increased of the electrical current (Aji ampere), with statistically significant difference (p<0.05). To the other study we evaluated the validity of reflexology and corona discharge (Kirlian) photography by applying BIOCERAMIC Resonance and small adhesive patches made from the BIOCERAMIC material. Significant differences were evident on four out of five different zones of the computerized images. CONCLUSION: Our findings suggest the existence of presupposed virtual channels or reflex points on the skin surface of the feet, hands, and ears that connect or somehow reflect back to specific internal organs, as mapped out on standard charts found in reflexology. Furthermore, the depicted corona intensities from five zones shown on a computer screen of corona discharge photography seem to indicate that the volunteer subjects are affected by the BIOCERAMIC patches. This study demonstrates the operation of the BIOCERAMIC Resonance device is able to produce weak force field through the body, which is objectively measurable and thereby scientifically integrating the concepts of reflexology, meridian channels and biofield therapy.

Inspiratory muscle training in bronchiectasis patients: a prospective randomized controlled study.

OBJECTIVE: To investigate the efficacy and feasibility of home-based inspiratory muscle training in patients with bronchiectasis. DESIGN: A prospective, single-blind, randomized, controlled study. SETTING: Outpatient clinic of a tertiary care medical centre. METHODS: Twenty-six patients with bronchiectasis were randomly divided into inspiratory muscle training and control groups. In the inspiratory muscle training group (n = 13), the training programme started with an intensity of 30% maximal inspiratory pressure (MIP), which was increased by 2 cmH(2)O each week, for 30 minutes daily, 5 days a week for eight weeks. The control group (n = 13) did not receive inspiratory muscle training. Main outcome measures included spirometry, resting oxyhaemoglobin saturation by pulse oximetry (SpO(2)), lowest SpO(2) and Borg Scale during 6-minute walking tests, 6-minute walking distance (6MWD), 6-minute walking work (6M(work)), MIP, maximal expiratory pressure (MEP) and St George's Respiratory Questionnaire. RESULTS: There were significant differences in change from baseline in 6MWD (411.9 (133.5) vs. 473.2 (117.2) m, P = 0.021), 6M(work) (21 051.0 (8286.7) vs. 23 915.5 (8343.0) kg-m, P = 0.022), MIP (60.8 (21.8) vs. 84.6 (29.0) cmH(2)O, P = 0.004), and MEP (72.3 (31.1) vs. 104.2 (35.7) cmH(2)O, P = 0.004) in the inspiratory muscle training group. Significant improvements in both MIP (23.8 (25.3) vs. 2.3 (16.4) cmH(2)O, adjusted P-value = 0.005) and MEP (31.9 (30.8) vs. 11.5 (20.8) cmH(2)O, adjusted P-value = 0.038) levels after adjusting for age by linear regression analysis were observed between groups. CONCLUSIONS: An eight-week home-based inspiratory muscle training is feasible and effective in improving both inspiratory and expiratory muscle strength, but has no effect on respiratory function and quality of life in patients with bronchiectasis.