Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons

Background: This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in patients with COPD and moderate-to-very severe airflow limitation, using evidence from direct (head-to-head) and indirect treatment comparisons. Methods: Two systematic literature reviews were conducted to identify direct comparisons (head-to-head randomized controlled trials [RCTs]) and indirect comparisons (network meta-analyses [NMAs]; indirect treatment comparisons; meta-analyses) in patients with COPD with moderate-to-very severe airflow limitation. Study/Analysis characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted from relevant publications. The review of indirect comparisons focused on NMAs reporting efficacy outcomes at 12 and 24 weeks of treatment (established durations of symptomatic studies in COPD recommended by regulators). Results: Direct comparisons: Four RCTs that provided head-to-head comparisons of LAMA/LABA FDCs were identified, and these varied in their study design, included patient population and reported endpoints. While some differences in lung function outcomes were noted, where assessed, LAMA/LABA FDCs had comparable efficacy in improving symptoms, health status, exacerbations, and comparable safety profiles. However, the differences in study methodology and patient characteristics between these studies made it difficult to draw generalizable conclusions regarding the comparative effectiveness of LAMA/LABA FDCs from the direct comparisons alone. Indirect comparisons: Six NMAs were identified that reported indirect comparisons between LAMA/LABA FDCs; five of these were within the pre-defined scope of this review. Although the scope of each NMA varied, all five concluded that LAMA/LABA FDCs were generally comparable in terms of lung function improvements, patient-reported outcomes, and safety (where assessed). Conclusion: Although there were some inconsistencies between the outcomes of RCTs and NMAs for lung function, the totality of lung function, symptoms, exacerbations, and safety data suggests that currently available LAMA/LABA FDCs have comparable efficacy and safety in patients with COPD and moderate-to-very severe airflow limitation

Measurement and analysis of needle penetration forces in industrial high-speed sewing machine

The industrial manufacturing of sewn products has always been one of the critical processes of the textile chain concerning quality assurance. Assuring the appropriate set-up and operation of all the machines, and thus the final seam quality, is a very complex task. Traditionally, this task is accomplished through empirical methods, with the machine setting and quality control relying on the skills of operators and technicians. This work presents an approach to a more knowledge-based and integrated process planning and control. A system was developed to measure and analyze the most important mechanical effects occurring during high-speed sewing. The paper will focus mainly on the measurement and evaluation of needle penetration and withdrawal force. After an overview of the system, the most important experimental results obtained in a series of experiments will be described

End of organised atheism. The genealogy of the law on freedom of conscience and its conceptual effects in Russia

In the current climate of the perceived alliance between the Russian Orthodox Church and the state, atheist activists in Moscow share a sense of juridical marginality that they seek to mitigate through claims to equal rights between believers and atheists under the Russian law on freedom of conscience. In their demands for their constitutional rights, including the right to political critique, atheist activists come across as figures of dissent at risk of the state's persecution. Their experiences constitute a remarkable (and unexamined in anthropology) reversal of political and ideological primacy of state-sponsored atheism during the Soviet days. To illuminate the legal context of the atheists’ current predicament, the article traces an alternative genealogy of the Russian law on freedom of conscience from the inception of the Soviet state through the law's post-Soviet reforms. The article shows that the legal reforms have paved the way for practical changes to the privileged legal status of organized atheism and brought about implicit conceptual effects that sideline the Soviet meaning of freedom of conscience as freedom from religion and obscure historical references to conscience as an atheist tenet of Soviet ethics

Automatic detection of airborne pollen: an overview

Pollen monitoring has traditionally been carried out using manual methods frst developed in the early 1950s. Although this technique has been recently standardised, it sufers from several drawbacks, notably data usually only being available with a delay of 3–9 days and usually delivered at a daily resolution. Several automatic instruments have come on to the market over the past few years, with more new devices also under development. This paper provides a comprehensive overview of all available and developing automatic instruments, how they measure, how they identify airborne pollen, what impacts measurement quality, as well as what potential there is for further advancement in the feld of bioaerosol monitoring.</p

An attemp to use a pulsed CO2 laser for decontamination of radioactive metal surfaces

There is a growing interest in laser radioactive decontamination of metal surfaces. It offers advantages over conventional methods: improved safety, reduction of secondary waste, reduced waste volume, acceptable cost. The main mechanism of cleaning by lasers is ablation. A pulsed TEA CO2 laser was used in this work for surface cleaning in order to show that ablation of metal surfaces is possible even at relatively low pulse energies, and to suggest that it could be competitive with other lasers because of much higher energy efficiencies. A brief theoretical analysis was made before the experiments. The laser beam was focused using a KBr-lens onto a surface contaminated with 137Cs (b-, t1/2 = 30.17 y). Three different metals were used: stainless steel, copper and aluminium. The ablated material was pumped out in an air atmosphere and transferred to a filter. The presence of activity on the filter was shown by a germanium detector-multichannel analyzer. The activity levels were measured by a GM counter. The calculated decontamination factors and collection factors showed that ablation occurs with a relatively high efficiency of decontamination. This investigation suggests that decontamination using a CO2 laser should be seriously considered

Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence

Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug-drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The AerosphereTM inhaler, formulated using co-suspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery

The impact of inhaler device regimen in patients with asthma or COPD

Many inhaler devices with varying handling requirements for optimal use are available for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Patients may be prescribed different device types for reliever and maintenance medications, which may lead to confusion and suboptimal device use. We aimed to understand whether simplifying inhaler regimens by employing a single device type in patients who use multiple devices or prescribing a device with which a patient was already experienced could improve clinical and economic outcomes in asthma and COPD management. A targeted literature search was performed and additional articles were identified through hand searching citations within screened publications. A total of 114 articles were included in the final review. Findings suggest that simplifying inhaler regimens by applying the same type of inhaler for concomitant inhaled medications over time minimizes device misuse, leading to improved clinical outcomes and reduced health care use in patients with asthma or COPD. Physicians should consider a patient's suitability for a device and training needs when prescribing an inhaled medication and before changing the medication type or dose, especially when suboptimal treatment outcomes are observed. Further research is required to determine whether consistent use of the same device type is associated with better treatment adherence and persistence in patients with asthma or COPD. Nevertheless, this literature review identified clinical benefits and reduced health care use with simplified inhaler regimens

Editorial: Interactions of nanoparticles with and within living organisms-What can we learn to improve efficacy of nanomedicine?

[no abstract available