Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis.

BACKGROUND: Pharmacological therapy for chronic obstructive pulmonary disease (COPD) is aimed at relieving symptoms, improving quality of life and preventing or treating exacerbations.Treatment tends to begin with one inhaler, and additional therapies are introduced as necessary. For persistent or worsening symptoms, long-acting inhaled therapies taken once or twice daily are preferred over short-acting inhalers. Several Cochrane reviews have looked at the risks and benefits of specific long-acting inhaled therapies compared with placebo or other treatments. However for patients and clinicians, it is important to understand the merits of these treatments relative to each other, and whether a particular class of inhaled therapies is more beneficial than the others. OBJECTIVES: To assess the efficacy of treatment options for patients whose chronic obstructive pulmonary disease cannot be controlled by short-acting therapies alone. The review will not look at combination therapies usually considered later in the course of the disease.As part of this network meta-analysis, we will address the following issues.1. How does long-term efficacy compare between different pharmacological treatments for COPD?2. Are there limitations in the current evidence base that may compromise the conclusions drawn by this network meta-analysis? If so, what are the implications for future research? SEARCH METHODS: We identified randomised controlled trials (RCTs) in existing Cochrane reviews by searching the Cochrane Database of Systematic Reviews (CDSR). In addition, we ran a comprehensive citation search on the Cochrane Airways Group Register of trials (CAGR) and checked manufacturer websites and reference lists of other reviews. The most recent searches were conducted in September 2013. SELECTION CRITERIA: We included parallel-group RCTs of at least 6 months' duration recruiting people with COPD. Studies were included if they compared any of the following treatments versus any other: long-acting beta2-agonists (LABAs; formoterol, indacaterol, salmeterol); long-acting muscarinic antagonists (LAMAs; aclidinium, glycopyrronium, tiotropium); inhaled corticosteroids (ICSs; budesonide, fluticasone, mometasone); combination long-acting beta2-agonist (LABA) and inhaled corticosteroid (LABA/ICS) (formoterol/budesonide, formoterol/mometasone, salmeterol/fluticasone); and placebo. DATA COLLECTION AND ANALYSIS: We conducted a network meta-analysis using Markov chain Monte Carlo methods for two efficacy outcomes: St George's Respiratory Questionnaire (SGRQ) total score and trough forced expiratory volume in one second (FEV1). We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (placebo). We assumed that treatment effects were similar within treatment classes (LAMA, LABA, ICS, LABA/ICS). We present estimates of class effects, variability between treatments within each class and individual treatment effects compared with every other.To justify the analyses, we assessed the trials for clinical and methodological transitivity across comparisons. We tested the robustness of our analyses by performing sensitivity analyses for lack of blinding and by considering six- and 12-month data separately. MAIN RESULTS: We identified 71 RCTs randomly assigning 73,062 people with COPD to 184 treatment arms of interest. Trials were similar with regards to methodology, inclusion and exclusion criteria and key baseline characteristics. Participants were more often male, aged in their mid sixties, with FEV1 predicted normal between 40% and 50% and with substantial smoking histories (40+ pack-years). The risk of bias was generally low, although missing information made it hard to judge risk of selection bias and selective outcome reporting. Fixed effects were used for SGRQ analyses, and random effects for Trough FEV1 analyses, based on model fit statistics and deviance information criteria (DIC). SGRQ SGRQ data were available in 42 studies (n = 54,613). At six months, 39 pairwise comparisons were made between 18 treatments in 25 studies (n = 27,024). Combination LABA/ICS was the highest ranked intervention, with a mean improvement over placebo of -3.89 units at six months (95% credible interval (CrI) -4.70 to -2.97) and -3.60 at 12 months (95% CrI -4.63 to -2.34). LAMAs and LABAs were ranked second and third at six months, with mean differences of -2.63 (95% CrI -3.53 to -1.97) and -2.29 (95% CrI -3.18 to -1.53), respectively. Inhaled corticosteroids were ranked fourth (MD -2.00, 95% CrI -3.06 to -0.87). Class differences between LABA, LAMA and ICS were less prominent at 12 months. Indacaterol and aclidinium were ranked somewhat higher than other members of their classes, and formoterol 12 mcg, budesonide 400 mcg and formoterol/mometasone combination were ranked lower within their classes. There was considerable overlap in credible intervals and rankings for both classes and individual treatments. Trough FEV1 Trough FEV1 data were available in 46 studies (n = 47,409). At six months, 41 pairwise comparisons were made between 20 treatments in 31 studies (n = 29,271). As for SGRQ, combination LABA/ICS was the highest ranked class, with a mean improvement over placebo of 133.3 mL at six months (95% CrI 100.6 to 164.0) and slightly less at 12 months (mean difference (MD) 100, 95% CrI 55.5 to 140.1). LAMAs (MD 103.5, 95% CrI 81.8 to 124.9) and LABAs (MD 99.4, 95% CrI 72.0 to 127.8) showed roughly equivalent results at six months, and ICSs were the fourth ranked class (MD 65.4, 95% CrI 33.1 to 96.9). As with SGRQ, initial differences between classes were not so prominent at 12 months. Indacaterol and salmeterol/fluticasone were ranked slightly better than others in their class, and formoterol 12, aclidinium, budesonide and formoterol/budesonide combination were ranked lower within their classes. All credible intervals for individual rankings were wide. AUTHORS' CONCLUSIONS: This network meta-analysis compares four different classes of long-acting inhalers for people with COPD who need more than short-acting bronchodilators. Quality of life and lung function were improved most on combination inhalers (LABA and ICS) and least on ICS alone at 6 and at 12 months. Overall LAMA and LABA inhalers had similar effects, particularly at 12 months. The network has demonstrated the benefit of ICS when added to LABA for these outcomes in participants who largely had an FEV1 that was less than 50% predicted, but the additional expense of combination inhalers and any potential for increased adverse events (which has been established by other reviews) require consideration. Our findings are in keeping with current National Institute for Health and Care Excellence (NICE) guidelines

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

First Observation of a Three-Resonance Structure in e+e−→e^+e^-\rightarrow{non-open} Charm Hadrons

We report the measurement of the cross sections for $e^+e^-$$\rightarrow${nOCH} (nOCH stands for non-open charm hadrons) with improved precision at center-of-mass energies from 3.645 to 3.871 GeV. We observe for the first time a three-resonance structure in the energy-dependent lineshape of the cross sections, which are $\mathcal R(3760)$, $\mathcal R(3780)$ and $\mathcal R(3810)$ with significances of $9.4\sigma$, $15.7\sigma$, and $9.8\sigma$, respectively. The $\mathcal R(3810)$ is observed for the first time. We found two solutions in analysis of the cross sections. For solution I [solution II], we measure the mass, the total width and the product of electronic width and nOCH decay branching fraction to be $(3805.8 \pm 1.1 \pm 2.7)$ [$(3805.8 \pm 1.1 \pm 2.7)$] MeV/$c^2$, $(11.6 \pm 2.6 \pm 1.9)$ [$(11.5 \pm 2.5 \pm 1.8)$] MeV, and $(10.8\pm 3.2\pm 2.3)$ [$(11.0\pm 2.9\pm 2.4)$] eV for the $\mathcal R(3810)$, respectively. In addition, we measure the branching fractions ${\mathcal B}({\mathcal R}(3760)$$\rightarrow${nOCH}$)=(24.5 \pm 13.4 \pm 27.4)\% [(6.8 \pm 5.4 \pm 7.6)\%]$ for the first time, and ${\mathcal B}(\mathcal R(3780)$$\rightarrow${nOCH}$)=(11.6 \pm 5.8 \pm 7.8)\% [(10.3 \pm 4.5 \pm 6.9)\%]$. Moreover, we determine the open-charm (OC) branching fraction ${\mathcal B}({\mathcal R}$$(3760)\rightarrow${OC}$)=(75.5 \pm 13.4 \pm 27.4)\% [(93.2 \pm 5.4 \pm 7.6)\%]$, which supports the interpretation of $\mathcal R(3760)$ as an OC pair molecular state, but contained a simple four-quark state component. The first uncertainties are from fits to the cross sections, and the second are systematic

Study of the doubly Cabibbo-suppressed decays Ds+→K+K+π−D^+_s\to K^+K^+\pi^- and Ds+→K+K+π−π0D^+_s\to K^+K^+\pi^-\pi^0

Based on 7.33 fb$^{-1}$ of $e^+e^-$ collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, the experimental studies of the doubly Cabibbo-suppressed decays $D^+_s\to K^+K^+\pi^-$ and $D^+_s\to K^+K^+\pi^-\pi^0$ are reported. We determine the absolute branching fraction of $D^+_s\to K^+K^+\pi^-$ to be (${1.23^{+0.28}_{-0.25}}({\rm stat})\pm0.06({\rm syst})$) $\times 10^{-4}$. No significant signal of $D^+_s\to K^+K^+\pi^-\pi^0$ is observed and the upper limit on its decay branching fraction at 90\% confidence level is set to be $1.7\times10^{-4}$.Comment: 10 pages, 4 figures, 4 table

Search for an invisible muon philic scalar X0X_{0} or vector X1X_{1} via J/ψ→μ+μ−+invisibleJ/\psi\to\mu^+\mu^-+\rm{invisible} decay at BESIII

A light scalar $X_{0}$ or vector $X_{1}$ particles have been introduced as a possible explanation for the $(g-2)_{\mu}$ anomaly and dark matter phenomena. Using $(8.998\pm 0.039)\times10^9$ \jpsi events collected by the BESIII detector, we search for a light muon philic scalar $X_{0}$ or vector $X_{1}$ in the processes $J/\psi\to\mu^+\mu^- X_{0,1}$ with $X_{0,1}$ invisible decays. No obvious signal is found, and the upper limits on the coupling $g_{0,1}'$ between the muon and the $X_{0,1}$ particles are set to be between $1.1\times10^{-3}$ and $1.0\times10^{-2}$ for the $X_{0,1}$ mass in the range of $1<M(X_{0,1})<1000$~MeV$/c^2$ at 90$\%$ confidence level.Comment: 9 pages 7 figure

Study of the decay J/ψ→ϕπ0ηJ/\psi \to \phi \pi^{0}\eta

Based on $(10.09 \pm 0.04) \times 10^9$ $J/\psi$ events collected with the BESIII detector operating at the BEPCII collider, a partial wave analysis of the decay $J/\psi \to \phi \pi^{0}\eta$ is performed. We observe for the first time two new structures on the $\phi\eta$ invariant mass distribution, with statistical significances of $24.0\sigma$ and $16.9\sigma$; the first with $J^{\rm PC}$ = $1^{+-}$, mass M = (1911 $\pm$ 6 (stat.) $\pm$ 14 (sys.))~MeV/$c^{2}$, and width $\Gamma =$ (149 $\pm$ 12 (stat.) $\pm$ 23 (sys.))~MeV, the second with $J^{\rm PC}$ = $1^{--}$, mass M = (1996 $\pm$ 11 (stat.) $\pm$ 30 (sys.))~MeV/$c^{2}$, and width $\Gamma$ = (148 $\pm$ 16 (stat.) $\pm$ 66 (sys.))~MeV. These measurements provide important input for the strangeonium spectrum. In addition, the $f_0(980)-a_0(980)^0$ mixing signal in $J/\psi \to \phi f_0(980) \to \phi a_0(980)^0$ and the corresponding electromagnetic decay $J/\psi \to \phi a_0(980)^0$ are measured with improved precision, providing crucial information to understand the nature of $a_0(980)^0$ and $f_0(980)$

Improved measurement of the decays η′→π+π−π+(0)π−(0)\eta' \to \pi^{+}\pi^{-}\pi^{+(0)}\pi^{-(0)} and search for the rare decay η′→4π0\eta' \to 4\pi^{0}

Using a sample of 10 billion $J/{\psi}$ events collected with the BESIII detector, the decays $\eta' \to \pi^{+}\pi^{-}\pi^{+}\pi^{-}$, $\eta' \to \pi^{+}\pi^{-}\pi^{0}\pi^{0}$ and $\eta' \to 4 \pi^{0}$ are studied via the process $J/{\psi}\to\gamma\eta'$. The branching fractions of $\eta' \to \pi^{+}\pi^{-}\pi^{+}\pi^{-}$ and $\eta' \to \pi^{+}\pi^{-}\pi^{0}$ $\pi^{0}$ are measured to be $( 8.56 \pm 0.25({\rm stat.}) \pm 0.23({\rm syst.}) ) \times {10^{ - 5}}$ and $(2.12 \pm 0.12({\rm stat.}) \pm 0.10({\rm syst.})) \times {10^{ - 4}}$, respectively, which are consistent with previous measurements but with improved precision. No significant $\eta' \to 4 \pi^{0}$ signal is observed, and the upper limit on the branching fraction of this decay is determined to be less than $1.24 \times {10^{-5}}$ at the $90\%$ confidence level. In addition, an amplitude analysis of $\eta' \to \pi^{+}\pi^{-}\pi^{+}\pi^{-}$ is performed to extract the doubly virtual isovector form factor $\alpha$ for the first time. The measured value of $\alpha=1.22 \pm 0.33({\rm stat.}) \pm 0.04({\rm syst.})$, is in agreement with the prediction of the VMD model

Search for hidden-charm tetraquark with strangeness in e+e−→K+Ds∗−D∗0+c.c.e^{+}e^{-}\rightarrow K^+ D_{s}^{*-} D^{*0}+c.c.

We report a search for a heavier partner of the recently observed $Z_{cs}(3985)^{-}$ state, denoted as $Z_{cs}^{\prime -}$, in the process $e^{+} e^{-}\rightarrow K^{+}D_{s}^{*-}D^{* 0}+c.c.$, based on $e^+e^-$ collision data collected at the center-of-mass energies of $\sqrt{s}=4.661$, 4.682 and 4.699 GeV with the BESIII detector. The $Z_{cs}^{\prime -}$ is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate $K^+$ recoil-mass spectra, which are probed for a potential contribution from $Z_{cs}^{\prime -}\to D_{s}^{*-}D^{* 0}$ ($c.c.$). We find an excess of $Z_{cs}^{\prime -}\rightarrow D_{s}^{*-}D^{*0}$ ($c.c.$) candidates with a significance of $2.9\sigma$, after considering systematic uncertainties, at a mass of $(4123.5 \pm 0.7_{\mathrm{stat.}} \pm 1.1_{\mathrm{syst.}}) \mathrm{MeV}/c^{2}$. As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross section and the branching fraction of $Z_{cs}^{\prime-}\rightarrow D_{s}^{*-}D^{* 0}$, $\sigma^{\rm Born}\cdot\mathcal{B}$ at the three energy points, under different assumptions of the $Z_{cs}^{\prime -}$ mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV. Under various mass and width assumptions, the upper limits of $\sigma^{\rm Born}\cdot\mathcal{B}$ are found to lie in the range of $2\sim6$, $3\sim7$ and $3\sim6$ pb at $\sqrt{s}=4.661$, 4.682 and 4.699 GeV, respectively. The larger data samples that will be collected in the coming years will allow a clearer picture to emerge concerning the existence and nature of the $Z_{cs}^{\prime -}$ state.Comment: 17 pages, 7 figure

Production of doubly-charged Δ\Delta baryon in e+e−e^{+}e^{-} annihilation at energies from 2.3094 to 2.6464 GeV

The processes $e^{+}e^{-} \to \Delta^{++}\bar{\Delta}^{--}$ and $e^{+}e^{-}\to \Delta^{++} \bar{p} \pi^{-} + c.c.$ are studied for the first time with $179~{\rm pb}^{-1}$ of $e^{+}e^{-}$ annihilation data collected with the BESIII detector at center-of-mass energies from $2.3094$ GeV to $2.6464$ GeV. No significant signal for the $e^{+}e^{-}\to \Delta^{++}\bar{\Delta}^{--}$ process is observed and the upper limit of the Born cross section is estimated at each energy point. For the process $e^{+}e^{-} \to \Delta^{++} \bar{p} \pi^{-} + c.c.$, a significant signal is observed at center-of-mass energies near 2.6454 GeV and the corresponding Born cross section is reported.Comment: 10 pages, 4 figure

Measurement of the C ⁣PC\!P-even fraction of D0→K+K−π+π−D^0\to K^+K^-\pi^+\pi^-

A determination of the $C\!P$-even fraction $F_+$ in the decay $D^0 \to K^+K^-\pi^+\pi^-$ is presented. Using $2.93$ fb$^{-1}$ of $e^+e^-\to\psi(3770)\to D\bar{D}$ data collected by the BESIII detector, one charm meson is reconstructed in the signal mode and the other in a $C\!P$ eigenstate or the decay $D\to K_{S, L}^0\pi^+\pi^-$. Analysis of the relative rates of these double-tagged events yields the result $F_+ = 0.730 \pm 0.037 \pm 0.021$, where the first uncertainty is statistical and the second is systematic. This is the first model-independent measurement of $F_+$ in $D^0 \to K^+K^-\pi^+\pi^-$ decays.Comment: 13 pages, 5 figure