A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

Introduction: Comparative data on the efficacies of long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) combinations for the treatment of moderate-to-very-severe chronic obstructive pulmonary disease (COPD) are limited. The aim of this Bayesian network meta-analysis (NMA) is to assess the relative efficacies of available open combinations (delivered via separate inhalers) and fixed-dose combinations (FDCs, delivered via a single inhaler). Methods: We conducted a systematic literature review with the aim of identifying randomized controlled trials (RCTs) of =8-week duration in adults aged =40 years with COPD that compared LAMA + LABA combinations with each other, with tiotropium (TIO), or with placebo. Data on changes from baseline in trough forced expiratory volume in 1 s (FEV1) and on St George’s Respiratory Questionnaire (SGRQ) total score, the Transition Dyspnea Index (TDI) focal score, and rescue medication use at 12 and 24 weeks were extracted from these RCTs and analyzed using a NMA in a Bayesian framework. Results: Data from 44 RCTs were included in the NMA. All FDCs showed improvements relative to placebo in terms of trough FEV1, SGRQ total score, and TDI focal score above clinically relevant thresholds, with the exception of TIO/olodaterol and aclidinium/formoterol, both of which failed to show clinically relevant improvements in SGRQ score at 24 weeks. All FDCs demonstrated reduced rescue medication use versus placebo. Open combinations demonstrated improved efficacy in all outcomes versus placebo, but these improvements did not consistently exceed clinically relevant thresholds for SGRQ and TDI scores. All once-daily FDCs showed improved efficacy versus TIO, but improvements were less consistently observed versus TIO with open dual combinations and combinations containing formoterol or salmeterol administered twice daily. Relative probabilities of improvement between FDCs highlighted potential between-class differences for trough FEV1 but suggested little potential for differences in patient-reported outcomes. Conclusion: LAMA + LABA combinations generally showed improved outcomes versus placebo and TIO. FDCs appeared to perform better than open dual combinations. A potential effectiveness gradient was observed between FDCs for objectively assessed functional outcomes, although further prospective trials are required to confirm these findings. Funding: GSK

Momentum-transfer model of valence-band photoelectron diffraction

Recent instrumental progress of valence-band photoemission in the X-ray range allows uncovering bulk- and surface-related electronic properties. Four-dimensional recording of energy and momentum-vector gives access to the complete spectral-density function. Systematic measurements for a number of transition metals between 15 eV-6 keV reveal unexpected strong intensity modulations due to photoelectron diffraction. Here, we present a graphical model that illustrates the role of momentum-conservation in Fermi’s Golden-Rule in an intuitive way. Intensity enhancement or reduction by factors >5 are confined to small energy- and momentum-intervals (widths 0.03 Å−1 and 200 meV). Laue-type diffraction involves the photon momentum and is intrinsic in the photoemission process, in accordance with Pendry’s final-state-model. At higher energies, Kikuchi-diffraction imprints additional modulations on valence-band-patterns and quasi-elastic background. The absence of photon-momentum transfer uncovers the extrinsic nature of Kikuchi-diffraction. For Re at 30 K and 3.4 keV the relative weight of the Kikuchi-branch is comparable to the Laue-branch, whereas at 6 keV the Kikuchi-branch prevails

Clinical studies of dental erosion and erosive wear

Item does not contain fulltextWe define erosion as a partial demineralisation of enamel or dentine by intrinsic or extrinsic acids and erosive tooth wear as the accelerated loss of dental hard tissue through the combined effect of erosion and mechanical wear (abrasion and attrition) on the tooth surface. Most experts believe that during the last decade there has been a significant increase in the prevalence and severity of erosive tooth wear, particularly in adolescents. Even when erosive wear occurs in its milder forms, this is a matter of concern, as it may compromise the integrity of an otherwise healthy dentition in later life. The erosive wear process is complicated and modified by many chemical, behavioural and associated processes in the mouth. If interventions are to be developed it is therefore important that in vivo methods are developed to assess the outcomes of the erosion and erosive wear processes and the effects of interventions upon them. This paper discusses potential methods of investigating erosion and erosive wear in vivo and the difficulties associated with clinical studies