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Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity, and facilitate patients’ compliance. This task is well-served by the following new form of therapy: inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. In adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment—regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach, or alternative second-line strategies—we propose that the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

In this article, the authors propose the study revealed that we need to search for the biographies and books of the remaining Mongolian lama. Luvsanjambaa is one of the Mongolian lamas (monks) who wrote many books and works in the Tibetan language and a disciple of the Dalai Günii Khüree, who lived from the last half of the 19th century to the beginning of the 20th century. The contents of his books indicate that Luvsanjambaa is a person who has the talent to write books and the ability to teach. He wrote his books for the Mongolian VIII Bogd Agvaan Luvsan Choijinnyam Danzin Vanchüg, Bigchüsumadi, Lama Luvsan Chimed Dorj, Namjal Sodnom Vanchüg , Dagva Luvsan, Tsorj lama Luvsan Tseveen Ravdan of the Western Monastery (Shangkh Monastery was located in Kharkhorin soum area of Ӧverkhangai province of present-day Mongolia) and respecting them as teachers. Among the books and works of these high lamas, the books of the VIII Bogd Agvaan Luvsan Choijinnyam Danzin Vanchüg, lama Luvsan Chimed Dorj and Namjal Sodnom Vanchüg, and the Tsorj lama Luvsan Tseveen Ravdan of the Western Monastery have now entered the circulation of current academic research. Also, it is clear that Luvsanjamba’s books written in the Tibetan language are valuable materials for the history of Mongolian religion, the study of religious rituals, and the study of Mongolian historical literature written in Tibetan.

Background: Assessment of long leg radiographs (LLRs) in pediatric orthopedic patients is an important but time-consuming routine task for clinicians. The goal of this study was to evaluate the performance of artificial intelligence (AI)-based leg angle measurement assistant software (LAMA) in measuring LLRs in pediatric patients, compared to traditional manual measurements. Methods: Eligible patients, aged 11 to 18 years old, referred for LLR between January and March 2022 were included. The study comprised 29 patients (58 legs, 377 measurements). The femur length, tibia length, full leg length (FLL), leg length discrepancy (LLD), hip–knee–ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle (mMPTA) were measured automatically using LAMA and compared to manual measurements of a senior pediatric orthopedic surgeon and an advanced practitioner in radiography. Results: Correct landmark placement with AI was achieved in 76% of the cases for LLD measurements, 88% for FLL and femur length, 91% for mLDFA, 97% for HKA, 98% for mMPTA, and 100% for tibia length. Intraclass correlation coefficients (ICCs) indicated moderate to excellent agreement between AI and manual measurements, ranging from 0.73 (95% confidence interval (CI): 0.54 to 0.84) to 1.00 (95%CI: 1.00 to 1.00). Conclusion: In cases of correct landmark placement, AI-based algorithm measurements on LLRs of pediatric patients showed high agreement with manual measurements. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location. [ABSTRACT FROM AUTHOR]

The sculpture "Arhat" (2114 ДВ) in the Buddhist collection of The Bohdan and Varvara Khanenko National Museum of Arts grasps the particular attention of the scholars taking into account its connection with the famous persons - the 13th Dalai Lama, Pyotr Kozlov, and most likely with Nicholas Roerich and his elder son George Roerich. According to the memorial sign on the sculpture, the art piece is the 13th Dalai Lama's present to Russian traveler Pyotr Kozlov in 1905 at Urga, capital of Mongolia. The "Arhat" was bought by the museum in 1969 as a part of a big collection of Buddhist art from Velichko V. S. (Moscow). The article touches on the historical events that forced the Tibetan ruler to arrive in Urga in 1905, and on the basis of documents and eyewitness accounts, sheds light on the circumstances of the Dalai Lama's meeting with Pyotr Kozlov. The authors provide some indirect arguments that "Velichko's collection" could belong to the Roerich family. The authors also give comments on the iconography of the sculpture, identifying it as an arhat or as a teacher. Arguments are also given on the sculpture's origin and dating - Tibet, the 19th century - not later than 1905. Besides, the results of x-ray fluorescence spectroscopy are revealed in the article. It was shown that the figure was made from two different types of metal - copper (torso, shoulders, and legs) and brass with a high percentage of zinc (hands and ears). Surface of the figure is artificially patinated. Collecting all data authors propose to make the corrections in the inventory information of the sculpture. [ABSTRACT FROM AUTHOR]

Copyright of Trabalhos em Lingüística Aplicada is the property of Universidade Estadual de Campinas - Portal de Periodicos Eletronicos Cientificos and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Assessment of long leg radiographs (LLRs) in pediatric orthopedic patients is an important but time-consuming routine task for clinicians. The goal of this study was to evaluate the performance of artificial intelligence (AI)-based leg angle measurement assistant software (LAMA) in measuring LLRs in pediatric patients, compared to traditional manual measurements. Methods: Eligible patients, aged 11 to 18 years old, referred for LLR between January and March 2022 were included. The study comprised 29 patients (58 legs, 377 measurements). The femur length, tibia length, full leg length (FLL), leg length discrepancy (LLD), hip–knee–ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle (mMPTA) were measured automatically using LAMA and compared to manual measurements of a senior pediatric orthopedic surgeon and an advanced practitioner in radiography. Results: Correct landmark placement with AI was achieved in 76% of the cases for LLD measurements, 88% for FLL and femur length, 91% for mLDFA, 97% for HKA, 98% for mMPTA, and 100% for tibia length. Intraclass correlation coefficients (ICCs) indicated moderate to excellent agreement between AI and manual measurements, ranging from 0.73 (95% confidence interval (CI): 0.54 to 0.84) to 1.00 (95%CI: 1.00 to 1.00). Conclusion: In cases of correct landmark placement, AI-based algorithm measurements on LLRs of pediatric patients showed high agreement with manual measurements.

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting β2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile.

Juan José Soler-Cataluña,1– 3 José Luis Izquierdo,4,5 Mónica Juárez Campo,6 Antoni Sicras-Mainar,7 Javier Nuevo6 1Pneumology Department, Hospital Arnau de Vilanova-Lliria, Valencia, Spain; 2Medicine Department, Universitat de València, Valencia, Spain; 3CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 4Medicine and Medical Specialties Department, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain; 5Respiratory Medicine Department, Hospital Universitario de Guadalajara, Guadalajara, Spain; 6Medical Department, AstraZeneca MC, Madrid, Spain; 7Health Economics and Outcomes Research Department, Atrys Health SA, Barcelona, SpainCorrespondence: Juan José Soler-Cataluña, Pneumology Department, Hospital Arnau de Vilanova-Lliria, Carrer de Sant Clement, 12, València, 46015, Spain, Tel +34 961 97 60 00, Fax +34 963868580, Email jjsoler@telefonica.netPurpose: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity and mortality, with a considerable consumption of healthcare resources (HRU). This study aims to obtain real world evidence regarding the consequences of COPD exacerbations and to provide updated data on the burden of this disease and its treatment.Patients and Methods: A retrospective study in seven Spanish regions was conducted among COPD patients diagnosed between 1/01/2010 and 31/12/2017. The index date was the diagnosis of COPD and patients were followed until lost to follow-up, death or end of the study, whichever occurred first. Patients were classified by patient pattern (incident or prevalent), type and severity of exacerbations, and treatments prescribed. Demographic and clinical characteristics were evaluated, together with the incidence of exacerbations, comorbidities, and the use of HRU, during the baseline (12 months before the index date) and the follow-up periods by incident/prevalent and treatment prescribed. Mortality rate was also measured.Results: The study included 34,557 patients with a mean age of 70 years (standard deviation: 12). The most frequent comorbidities were diabetes, osteoporosis, and anxiety. Most patients received inhaled corticosteroids (ICS) with long-acting beta agonists (LABA), or long-acting muscarinic agonists (LAMA), followed by LABA with LAMA. Incident patients (N=8229; 23.8%) had fewer exacerbations than prevalent patients (N=26328; 76.2%), 0.3 vs 1.2 exacerbations per 100 patient-years. All treatment patterns present a substantial disease burden, which seems to increase with the evolution of the disease (ie moving from initial treatments to combination therapies). The overall mortality rate was 40.2 deaths/1000 patient-years. General practitioner visits and tests were the HRU most frequently required. The frequency and severity of exacerbations positively correlated with the use of HRU.Conclusion: Despite receiving treatment, patients with COPD suffer a considerable burden mainly due to exacerbations and comorbidities, which require a substantial use of HRU.Keywords: COPD, real-world evidence, clinical practice, triple therapy, ICS, LABA, LAMA

What is this summary about? Inhaled corticosteroids (ICS) are a type of medication delivered via an inhaler device that are commonly used in the treatment of asthma. ICS can also be used to treat chronic obstructive pulmonary disease (COPD), a progressive respiratory condition in which the lungs become worse over time. However, unlike in asthma, ICS are only effective in a small proportion of people with COPD. ICS can cause significant side effects in people with COPD, including pneumonia. Because of this, guidelines written by COPD experts recommend that ICS should largely be prescribed to people with COPD whose symptoms flare up frequently and become difficult to manage (episodes known as exacerbations). Despite this guidance, records collected from routine clinical practice suggest that many healthcare professionals prescribe ICS to people with COPD who do not have frequent exacerbations, putting them at unnecessary risk of side effects. The over-prescription of ICS in COPD may partly be due to the recent introduction of single-inhaler combination therapies, which combine ICS with other medicines (bronchodilators). This ‘one inhaler for all’ approach is a concerning trend as it goes against global COPD treatment guidelines, which recommend ICS use in only a small proportion of people. This is a plain language summary of a review article originally published in the journal NPJ Primary Care Respiratory Medicine. In this review, we investigate the benefits and risks of ICS use in COPD. Using data from both randomized controlled trials (RCTs) and observational studies, we explain which people benefit from ICS use, and why health regulatory bodies have concluded that ICS do not help people with COPD to live longer. Lastly, we provide practical guidance for doctors and people with COPD regarding when ICS should be prescribed and when they should be withdrawn.

Copyright of Humanities & Educational Sciences Journal is the property of Humanities & Educational Sciences Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Clinical Trial Registration: ECR/159/Inst/WB/2013/RR-20 Background: Glycopyrronium bromide (a long-acting antimuscarinic agent: LAMA) appears pharmacokinetically suitable for testing bronchodilator responsiveness as salbutamol (short-acting β2-agonist: SABA). Exploring the feasibility, acceptability, degree of reversibility with glycopyrronium, and its comparison with that of salbutamol may be intriguing. Methods: New, consecutive, and willing outpatient attendees in the same season of the two consecutive years with chronic obstructive pulmonary disease (FEV1/FVC

In South America inhabit an endemic group of ungulates adapted to extreme environments: the South American camelids (SAC), a key component of the Andean biocultural heritage. Until today, SAC are the most important factor of Andean economies and social and ritual life. SAC include two wild species, the guanaco (Lama guanicoe) and the vicuña (Vicugna vicugna), and two domestic species, the llama (Lama glama) and the alpaca (Vicugna pacos). Endoparasitosis are one of the most common diseases in SAC, and have great economic and health relevance. Despite this, there is a lack of knowledge on this concern. The main objective of this work was to conduct the first systematic review of the diversity of gastrointestinal parasites of SAC throughout the entire native range of distribution and to identify several gaps in knowledge. The PRISMA protocol was performed and a total of 101 documents were summarized. At least 36 parasitic helminths and five Eimeria spp. were registered. This work highlights the need for a greater number of works to know with more certainty the parasitic fauna of camelids in the past and present, in order to achieve predictions that allow proper management of camelids for their future conservation. Furthermore, concerted research efforts are needed to understand the biology, epidemiology, diagnosis and distribution of the parasitosis of SAC along the entire distribution range to guide conservation decisions.

Abstract Background Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes. Methods A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted. Results Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities. Conclusions LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.

Background: Glycopyrronium bromide (a long‑acting antimuscarinic agent: LAMA) appears pharmacokinetically suitable for testing bronchodilator responsiveness as salbutamol (short‑acting β2‑agonist: SABA). Exploring the feasibility, acceptability, degree of reversibility with glycopyrronium, and its comparison with that of salbutamol may be intriguing. Methods: New, consecutive, and willing outpatient attendees in the same season of the two consecutive years with chronic obstructive pulmonary disease (FEV1 /FVC <0.07; FEV1 <80% of predicted) were subjected to serial responsiveness with inhalation of salbutamol first followed by 50 µg dry powder glycopyrronium [Salbutamol‑ Glycopyrronium] (phase‑1) in the first year and glycopyrronium followed by salbutamol [Glycopyrronium‑ Salbutamol] (phase‑2) in the following year. We looked for the acceptability, adverse reactions, and degree of changes in FEV1, FVC, FEV1/FVC, and FEF25‑75 with comparison between the two groups. Results: The [Salbutamol‑ Glycopyrronium] group (n = 86) were similar in age, body mass index, and FEV1 to the [Glycopyrronium‑ Salbutamol] group (n = 88). Both the agents could make a significant (P <.0001) improvement in the parameters independently or as add‑on when used serially in alternate orders. The intergroup difference at no stage was significant. The sensitive patients to salbutamol (n = 48), glycopyrronium (n = 44), and both (n = 12) have improvement of 165, 189, and 297 mL while a both‑insensitive group (n = 70) had barely 44 mL of improvement. The protocol was universally accepted without any adverse events. Conclusion: Serial testing of salbutamol and glycopyrronium responsiveness in alternate orders provides an insight regarding the independent and the add‑on effects of these two agents. About 40% of our chronic obstructive pulmonary disease patients had no clinically appreciable difference in FEV1 with the salbutamol + glycopyrronium combination inhalation. [ABSTRACT FROM AUTHOR]

BackgroundSmoking is a major risk factor for COPD and may impact the efficacy of COPD treatments; however, a large proportion of COPD patients continue to smoke following diagnosis.MethodsThis post-hoc analysis of pooled data from the replicate 12-week, placebo-controlled GEM1 and GEM2 studies assessed the impact of smoking status on the efficacy and safety of glycopyrrolate 15.6 μg twice daily vs placebo in patients with moderate-to-severe COPD. Data from 867 patients enrolled in GEM1 and GEM2 were pooled for analysis and grouped by smoking status (57% current smokers, 43% ex-smokers). Forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h, trough FEV1, forced vital capacity, St George's Respiratory Questionnaire (SGRQ) total score, COPD assessment test (CAT) score, transition dyspnea index (TDI) focal score, daily symptom scores, and rescue medication use were assessed in current smokers and ex-smokers. Incidences of adverse events (AEs) and serious AEs (SAEs) were also assessed.ResultsTreatment with glycopyrrolate resulted in significant improvements in all lung function measures, independent of smoking status. In both current and ex-smokers, changes from baseline in trough FEV1 were less marked in patients taking inhaled corticosteroids (ICS) than those not receiving ICS. Changes from baseline in SGRQ total score and rescue medication use were significantly greater with glycopyrrolate compared with placebo, regardless of smoking status. Changes in the CAT score, TDI focal score, and daily symptom scores significantly improved versus placebo, but only in current smokers. Improvements in patient-reported outcomes (PROs) with glycopyrrolate relative to placebo were numerically greater in current smokers than ex-smokers. The incidences of AEs and SAEs were similar regardless of smoking status.ConclusionsIn this post-hoc analysis of GEM1 and GEM2, glycopyrrolate use led to significant improvements in lung function, independent of baseline smoking status; improvements were less marked among patients receiving background ICS, regardless of baseline smoking status. Improvements in PROs were greater with glycopyrrolate than placebo, and the magnitude of changes was numerically greater among current smokers. The safety profile of glycopyrrolate was comparable between current smokers and ex-smokers.

Cristina Rebordosa,1 Estel Plana,2 Annalisa Rubino,3 Jaume Aguado,2 David Martinez,2 Alejhandra Lei,4 Sami Daoud,5 Nuria Saigi-Morgui,1 Susana Perez-Gutthann,1 Elena Rivero-Ferrer1 1Department of Epidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain; 2Department of Biometrics, RTI Health Solutions, Barcelona, Spain; 3Epidemiology, Respiratory and Immunology, AstraZeneca, Cambridge, UK; 4Patient Safety Biopharma, AstraZeneca, Barcelona, Spain; 5BioPharmaceuticals Research and Development, Late-Stage Development Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USACorrespondence: Cristina Rebordosa, RTI Health Solutions, Department of Epidemiology and Risk Management, Av. Diagonal, 605, 9-1, Barcelona, 08028, Spain, Tel +34.93.362.2807, Fax +34.93.760.8507, Email crebordosa@rti.orgBackground: The long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safety study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists.Purpose: To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA.Patients and Methods: This population-based cohort study included patients with COPD aged ≥ 40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables.Results: The study included 11,121 new users of aclidinium, 4804 of aclidinium/formoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/formoterol) to 12.4 (LAMA/LABA), for stroke ranged from 4.8 (aclidinium/formoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/formoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95 [0.60– 1.52], and highest for LAMA/LABA, 1.23 [0.91– 1.67]), stroke (lowest for aclidinium/formoterol, 0.64 [0.39– 1.06], and highest for tiotropium, 1.02 [0.81– 1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75– 1.16], and highest for LAMA/LABA, 1.24 [0.97– 1.59]).Conclusion: Risks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA.Keywords: aclidinium, acute myocardial infarction, LAMA, stroke, United Kingdom

Peter Dickinson's acclaimed English novel of 1979, Tulku , is primarily an exploration of the Tibetan Buddhist custom of discerning in children reincarnations of deceased spiritual leaders who are subsequently trained to assume positions of responsibility. This fascinating work also examines other dimensions of contemplative monastic Buddhism in a remote Himalayan setting, chiefly in a lamasery. On a broader scale, Dickinson addresses such themes as the supposedly peaceful nature of the national religion in question, relations between that faith and Christianity, the possibility of finding merit in religions other than one's own, and the role of illusion in religious belief and practice. In the present article these matters are considered against the backdrop of evolving Western images of and attitudes towards Tibet generally, its form of Buddhism in particular, and the problematic practice of discovering reincarnated tulkus. [ABSTRACT FROM AUTHOR]

Marcus Sim,1 Anthony Yii,1 Xiaomeng Xu,2 Priti Bahety,3 Chee Hong Loh,1 Aldo Amador Navarro Rojas,4 Dominique Milea,2 Augustine Tee1 1Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore; 2Value Evidence & Outcomes, Greater China and Intercontinental, GSK, Singapore, Singapore; 3Medical Affairs, GSK, Singapore, Singapore; 4Respiratory & Specialty Medical Lead, Greater China and Intercontinental, GSK, Singapore, SingaporeCorrespondence: Marcus Sim, Department of Respiratory and Critical Care Medicine, Changi General Hospital, 2 Simei Street 3, Singapore, 529889, Singapore, Tel +65 6788 8833, Email marcus.sim@mohh.com.sgIntroduction: There is limited real-world evidence regarding clinical practice for chronic obstructive pulmonary disease (COPD) in Singapore. We compared baseline clinical characteristics and evaluated outcomes in patients with COPD who initiated treatment with either a long-acting muscarinic antagonist (LAMA) or a LAMA and a long-acting β2-agonist (LAMA+LABA).Methods: This was a single-center observational study at Changi General Hospital, Singapore. Routine clinical data (hospital visits, case management, lung function, laboratory/imaging results, medication orders) were collected and compiled into a data warehouse. Eligible patients with COPD were ≥ 40 years old and newly prescribed LAMA or LAMA+LABA during the enrollment period. Patient characteristics in the baseline period (6 months) were compared between treatments. Clinical worsening was measured as a composite endpoint, defined as the first of a change in maintenance treatment class or a moderate-to-severe exacerbation during follow-up (12 months).Results: In total, 261 patients were included in the baseline period (LAMA: 73; LAMA+LABA: 188). In the baseline period, patients receiving LAMA+LABA versus LAMA had significantly lower body mass index, higher COPD Assessment Test score and worse lung function, and numerically higher exacerbation history. Prevalence of comorbidities was similar between treatment groups. In follow-up, high rates of clinical worsening were observed regardless of treatment regimen (LAMA: 38/73 [52%]; LAMA+LABA: 86/188 [46%]). Median time-to-clinical worsening was 340 days for the LAMA cohort and the raw median 154 days (interquartile range: 44– 225) for the LAMA+LABA cohort. Median medication dispensation rate (0.86; interquartile range: 0.56– 1.00) was similar between treatments.Conclusion: Patients initiating treatment with LAMA+LABA had more severe COPD than patients prescribed LAMA. The proportion of patients experiencing clinical worsening was similarly high in both cohorts, suggesting that early identification and treatment optimization are necessary.Keywords: COPD treatment, database analysis, dual bronchodilator, LABA, LAMA, inhaler prescription

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.

Highlight removal is a critical and challenging problem. In view of the complex highlight phenomenon on the surface of smooth liquor bottles in natural scenes, the traditional highlight removal algorithms cannot semantically disambiguate between all-white or near-white materials and highlights, and the recent highlight removal algorithms based on deep learning lack flexibility in network architecture, have network training difficulties and have insufficient object applicability. As a result, they cannot accurately locate and remove highlights in the face of some small sample highlight datasets with strong pertinence, which reduces the performance of some tasks. Therefore, this paper proposes a fast highlight removal method combining U2-Net and LaMa. The method consists of two stages. In the first stage, the U2-Net network is used to detect the specular reflection component in the liquor bottle input image and generate the mask map for the highlight area in batches. In the second stage, the liquor bottle input image and the mask map generated by the U2-Net are input to the LaMa network, and the surface highlights of the smooth liquor bottle are removed by relying on the powerful image inpainting performance of LaMa. Experiments on our self-made liquor bottle surface highlight dataset showed that this method outperformed other advanced methods in highlight detection and removal. [ABSTRACT FROM AUTHOR]

Background: Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes. Methods: A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted. Results: Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities. Conclusions: LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes. [ABSTRACT FROM AUTHOR]

In South America inhabit an endemic group of ungulates adapted to extreme environments: the South American camelids (SAC), a key component of the Andean biocultural heritage. Until today, SAC are the most important factor of Andean economies and social and ritual life. SAC include two wild species, the guanaco (Lama guanicoe) and the vicuña (Vicugna vicugna) , and two domestic species, the llama (Lama glama) and the alpaca (Vicugna pacos). Endoparasitosis are one of the most common diseases in SAC, and have great economic and health relevance. Despite this, there is a lack of knowledge on this concern. The main objective of this work was to conduct the first systematic review of the diversity of gastrointestinal parasites of SAC throughout the entire native range of distribution and to identify several gaps in knowledge. The PRISMA protocol was performed and a total of 101 documents were summarized. At least 36 parasitic helminths and five Eimeria spp. were registered. This work highlights the need for a greater number of works to know with more certainty the parasitic fauna of camelids in the past and present, in order to achieve predictions that allow proper management of camelids for their future conservation. Furthermore, concerted research efforts are needed to understand the biology, epidemiology, diagnosis and distribution of the parasitosis of SAC along the entire distribution range to guide conservation decisions. [Display omitted] • Endoparasitosis are one of the most common diseases in SAC. • First review of parasites diversity of SAC throughout its total range of distribution. • At least 36 parasitic helminths and 5 Eimeria spp. were registered in camelids. • The registered parasites are mostly generalist parasites. • A better understanding of the extent and impact of parasites of SAC is needed. [ABSTRACT FROM AUTHOR]

Objective: To understand and recognise why some patients leave the medical facility against physicians medical advice as it has clear significance in identifying those at risk and planning interventions for them beforehand. Study Design: Exploratory Research. Setting: Department of Psychiatry, Gujranwala Medical Collage/ Teaching Hospital. Period: September 2018 to September 2019. Material & Methods: The record included 73 cases that left against medical advice. Results: Highest ratios of variables present in the patients who left AMA were educational level of patients up to matriculation (34.2%), unemployment (54.8%), primary diagnosis of schizophrenia (20.5%), residence in Gujranwala (57.5%), attending physician's residence up to 2 years (27.4%), and non availability of attendants (16.4%). Conclusion: Knowing what variables perpetuates the patient's need to leave against medical advice can help in taking preliminary measures to prevent it. [ABSTRACT FROM AUTHOR]

Introduction: Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.Methods: A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.Results: The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV1 versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.Conclusion: UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV1 at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments. [ABSTRACT FROM AUTHOR]

Introduction. The article examines historical sources dealing with Lama Zodbo-Arakba Samtanov, the Head Lama of Buddhists of the Kalmyk steppe in 1873–1886, in terms of interaction between the Russian state administration and Kalmyk Buddhists. Data and methods. The research is based on historical-descriptive and comparative methods of historical analysis. Its focus is on the archive documents, including the memorandum of 21 January 1880 directed by the Head Lama of Kalmyk Buddhists Zodbo-Arakba Samtanov to the Minister of State Property A. A. Liven and the 1886 article ”Smert´poslednego lamy” (Death of the Last Lama) in the local newspaper Astrakhanskii spravochnyi listok. Results. This paper has examined the historical sources pertaining to Lama Samtanov’s biography. Of particular interest for the research was the evidence of his participation in the interdepartment discussions on a number of urgent issues of the second half of the nineteenth century, such as the staff of Kalmyk Buddhist monasteries being reduced and the traditional Buddhist education of Kalmyks being restricted. Also, the article focuses on the description of the ritual of Lama’s cremation that took place on 14 December 1886. Conclusions. The second half of the nineteenth century saw a more active interaction between the Buddhists of the Kalmyk steppe and Russian state ministeries and departments dealing with Kalmyk affairs. The Kalmyk senior lamas participated in a dialogue with Russian officials in an effort to defend their system of Buddhist monasteries and the traditional rules and customs of the local Buddhists. Lama Samtanov’s memorandum is a vivid example of interaction between Kalmyk Buddhists and the administration of the Russian Empire. The article ”Death of the Last Lama” in Astrakhanskii spravochnyi listok that describes the ritual of Lama’s cremation is not only a valuable source but also the evidence that shows some of the local journalists’ positive attitudes towards the Buddhist monasteries’ role in the life of Kalmyks in the late nineteenth century.

Chronic obstructive pulmonary disease (COPD) refers to a group of widely diffuse diseases that cause airflow blockage characterized by persistent respiratory symptoms such as dyspnea, chronic cough, recurrent wheezing, chronic sputum production, and progressive restricted airflow associated with exacerbations. COPD is the third leading cause of death worldwide and can only be treated not cured.Pulmonary function tests do not permit the identification of initial obstructive airways disease. Forced expiratory flow (FEF25-75), which calculates obstruction severity at small and medium bronchial airways levels, allows an early COPD diagnosis.We report a 72-year-old ex-smoker male not exposed to occupational risk with symptoms suggesting early COPD. Baseline pulmonary function tests were normal, except FEF25-75. The patient did not respond to the first 6 months of treatment with long-acting muscarinic antagonist (LAMA), whereas he showed a clear clinical and FEF25-75 response to 1-year treatment with LAMA associated with long-acting β2 agonist (LABA).This clinical case report highlights the usefulness of FEF25-75 evaluation in early COPD diagnosis and monitoring and confirms the efficacy of LAMA–LABA association for small airways obstruction treatment.

The llama (Lama glama) and the alpaca (L. pacos) form the group known as domesticated camelids. They belong to the family Camelidae of the order Artiodactyla (ungulates). They are separated from other ruminants in the infraorder Tylopoda (footed) because they differ in gastric morphology (three compartments), with the absence of antlers or horns, and replacement of hooves with callous pads ending in claws (Novoa and Wheeler, 1984). Camellias are tall, robust and the largest of the four camelid species. They are used to transport goods in Central and South America, where their meat is also used. The leather is used for shoes, sandals and bags. Their wool fiber is long and coarse, varying in color from white to black, and is used to make various clothing items. In our country, and in Europe in general, llamas and alpacas are used for leisure purposes and even as pets, in some cases their wool being used to create clothing products. [ABSTRACT FROM AUTHOR]

Cristina Rebordosa, 1 Estel Plana, 1 Annalisa Rubino, 2 Jaume Aguado, 1 Alejhandra Lei, 3 Sami Daoud, 4 Nuria Saigi-Morgui, 1 Susana Perez-Gutthann, 1 Elena Rivero-Ferrer 1 1RTI Health Solutions, Barcelona, Spain; 2Epidemiology, Respiratory and Immunology, AstraZeneca, Cambridge, UK; 3Patient Safety Biopharma, AstraZeneca, Barcelona, Spain; 4BioPharmaceuticals Research and Development, Late-Stage Development Research and Innovation, AstraZeneca, Gaithersburg, MD, USACorrespondence: Cristina RebordosaRTI Health Solutions, Av. Diagonal, 605, 9-1, Barcelona, 08028, SpainTel +34 93 241 7766Fax +34 93 760 8507Email crebordosa@rti.orgBackground: The long-acting anticholinergic (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adults with chronic obstructive pulmonary disease (COPD). A Post-Authorisation Safety Study (PASS) was initiated to assess potential cardiovascular safety concerns for aclidinium.Objective: To estimate the adjusted incidence rate ratio (IRR) for hospitalisation for heart failure in patients with COPD who were new users of aclidinium, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA were compared with initiators of LABA.Methods: This population-based cohort study included patients with COPD aged ≥ 40 years initiating COPD medications in the Clinical Practice Research Datalink (CPRD) GOLD in the United Kingdom from 2012 to 2017. Medications were identified via general practice prescriptions. The first-ever hospitalisations for heart failure were identified in the Hospital Episode Statistics, and general practitioner records from the CPRD. Poisson regression models were used to estimate the IRR for hospitalisation for heart failure in users of COPD medications versus LABA, adjusting for clinically relevant covariates.Results: The study included 4350 new users of aclidinium, 23,405 of tiotropium, 6977 of other LAMAs, 3122 of LAMA/LABA, 26,093 of LABA/ICS, and 5678 of LABA. Mean age was 69– 70 years across medication groups. Aclidinium users had the highest proportion of severe COPD, and LABA users had the lowest (35% vs 19%, respectively). Crude incidence rates per 1000 person-years for the first-ever hospitalisation for heart failure ranged from 6.9 in LABA to 9.5 in aclidinium. Using LABA as reference, adjusted IRRs (95% confidence interval) for first-ever hospitalisation for heart failure were 0.90 (0.53– 1.53) for aclidinium, 1.02 (0.69– 1.51) for tiotropium, 0.86 (0.50– 1.47) for other LAMAs, 1.09 (0.41– 2.92) for LAMA/LABA, and 1.01 (0.69, 1.48) for LABA/ICS.Conclusion: The study did not find increased risks of hospitalisations for heart failure in new users of aclidinium, tiotropium, other LAMAs, LAMA/LABA, and LABA/ICS compared with LABA.Keywords: aclidinium, LAMA, heart failure, United Kingdom

South American camelids (Lamini tribe) are represented by two genera and four species. Here we studied the skull anatomy of three of them, Lama glama , Lama guanicoe and Vicugna vicugna. The coexistence of these species in wide sectors of their distribution and the osteological homogeneity of these camelids constitute important factors that limit or even preclude identification at species level. This is particularly true in paleontological and archaeological contexts in which bones are the only elements to analyze, and complete or fragmentary remains are potentially recorded. Although some contributions dealing with interspecific differentiation of camelids are available currently, the clear distinction between these species through osteological remains is still a pending issue. The aim of this study was to find osteological characters that facilitate the determination of the analyzed species. For this, we analyzed a final sample comprised mainly adult specimens of 11 guanacos, 9 llamas and 18 vicuñas. We described and compared a diverse set of qualitative and quantitative osteological features of the skull, including foramina, processes, muscular scars, and other features of the cranium and mandible. The set of qualitative features included eight observations on the cranium and four on the mandible. The set of quantitative features included eight linear variables on the cranium and two on the mandible. We performed a Partial Least Squares Discriminant Analysis (PLS-DA) based on both qualitative and quantitative variables in order to differentiate camelids species. The best results were obtained when both types of variables were included in the analysis. The most robust characters for interspecific discrimination are those related to the muzzle, the mastoid foramen, the paraoccipital process, the lower incisors and the coronoid and condylar processes of the mandible. The morpho-functional meanings of some of these traits are discussed. This study can be considered as a contribution to future systematic studies and as a basic tool to carry out specific assignment of camelids through complete or partial remains in archaeological and paleontological contexts. [ABSTRACT FROM AUTHOR]

Nirupama Putcha,1 Ayca Ozol-Godfrey,2 Shahin Sanjar,2 Sanjay Sharma2 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Nirupama PutchaDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, JHAAC 4B.74, Baltimore, MD, 21224, USATel +1 410-550-0545Email nputcha1@jhmi.eduPurpose: Patients with COPD often have multiple coexisting comorbidities, affecting quality of life, morbidity and mortality. However, the prevalence and impact of comorbidities on the efficacy of bronchodilators in COPD is poorly understood.Patients and Methods: In this post hoc analysis, pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies of nebulized glycopyrrolate (GLY) in individuals with moderate-to-very-severe COPD were used to quantify comorbidities and assess their impact on treatment efficacy and safety.Results: Comorbidities that were most prevalent in the GOLDEN 3 and 4 study population were hypertension, high cholesterol and osteoarthritis. Participants were grouped based on their pre-specified comorbidity count into Group A (≤ 2 comorbidities; n=439) and Group B (> 2 comorbidities; n=854). Treatment with GLY resulted in significant improvements in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total scores, independent of comorbidity prevalence. A higher prevalence of cardiovascular disease (CVD) comorbidities was observed among individuals in Group B, compared with Group A. In a sub-analysis based on prevalence of CVD, treatment with GLY resulted in significant FEV1 improvements independent of CVD prevalence, although values were numerically higher in the CVD group. GLY also led to higher improvements in SGRQ scores in the CVD group. GLY was well tolerated regardless of comorbidity or CVD prevalence, with a lower incidence of serious adverse events compared with placebo.Conclusion: A simple comorbidity count demonstrated that a majority of patients with COPD in the GOLDEN 3 and 4 studies had multiple comorbidities, with CVD being common in those with high comorbidity count. Results from this post hoc analysis demonstrate that GLY improved FEV1 and SGRQ scores in individuals with COPD, independent of their comorbidities or CVD status.Keywords: comorbidities, COPD, cardiovascular disease, LAMA, nebulized glycopyrrolate

Donald P Tashkin,1 Ayca Ozol-Godfrey,2 Sanjay Sharma,2 Shahin Sanjar2 1Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA Health Sciences, Los Angeles, CA, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Donald P TashkinDivision of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA Health Sciences, Los Angeles, CA, 90095, USATel +1 310-825-3163Email dtashkin@mednet.ucla.eduBackground: Chronic bronchitis (CB) is one of the conditions that contribute to chronic obstructive pulmonary disease (COPD). Despite its widespread prevalence among patients with COPD and overall negative impact on treatment outcomes, the effect of CB on the efficacy of bronchodilator therapy has not been evaluated. The objective of this post hoc analysis is to assess the effect of nebulized glycopyrrolate (GLY) on lung function and health-related quality of life outcomes in patients with St George’s Respiratory Questionnaire (SGRQ)-defined CB at baseline.Methods: Pooled data from the replicate, 12-week GOLDEN 3 and 4 studies (N=861) were grouped by CB status at baseline. The endpoints reported are changes from baseline in trough forced expiratory volume in 1 second (FEV1), SGRQ and EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (EXACT-RS) scores. Safety of GLY was evaluated by monitoring the incidence of adverse events (AEs).Results: Following 12 weeks of treatment, GLY 25 μg twice-daily (BID) resulted in placebo-adjusted improvements from baseline in FEV1 of 77.1 mL and 124.4 mL in the CB and non-CB groups, respectively (p< 0.0001 vs placebo in both groups). Significant improvements in SGRQ total scores were observed with GLY 25 μg BID compared with placebo, regardless of baseline CB status. Although EXACT-RS improvements were noted in both CB and non-CB groups, significant improvements were observed only in the CB group. GLY 25 μg BID was generally well tolerated through 12 weeks of treatment, with a low incidence of AEs.Conclusion: Treatment with nebulized GLY 25 μg BID for 12 weeks resulted in significant improvements in lung function and SGRQ total scores, compared with placebo. Significant improvements in EXACT-RS total scores were observed only in the CB group. Together, these results support the use of GLY 25 μg BID in patients with COPD, regardless of their CB status.Keywords: chronic bronchitis, COPD, LAMA, nebulized glycopyrrolate

Nicola A Hanania,1 Abebaw M Yohannes,2 Ayca Ozol-Godfrey,3 Michael Tocco,3 Thomas Goodin,3 Sanjay Sharma,3 Shahin Sanjar3 1Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, 77030, USA; 2Department of Physical Therapy, Azusa Pacific University, Azusa, CA, USA; 3Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Nicola A HananiaSection of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USATel +1 713-873-3454Email hanania@bcm.eduBackground: Anxiety and depression (A/D) are common in patients with chronic obstructive pulmonary disease (COPD) and are often associated with lower adherence to treatment and worse patient-related outcomes. However, studies on the impact of comorbid A/D on responses to bronchodilators are limited.Methods: This post hoc analysis of pooled data (N=861) from the GOLDEN 3 and 4 studies compared the efficacy and safety of nebulized glycopyrrolate (GLY) 25 μg in patients with moderate-to-very-severe COPD, grouped by self-reported A/D. Changes in forced expiratory volume in 1 second (FEV1) and health-related quality of life determined by St George’s Respiratory Questionnaire (SGRQ) scores in patients with or without comorbid A/D (A/D [+] or A/D [–]) were examined following 12 weeks of GLY 25 μg twice-daily (BID) or placebo treatment.Results: A/D (+) patients were predominantly female, younger, included a higher proportion of current smokers, and had higher baseline SGRQ scores compared with the A/D (–) group. At 12 weeks, GLY resulted in placebo-adjusted improvements from baseline in FEV1 of 46.9 mL (p=0.19; not significant) and 106.7 mL (p< 0.0001), in the A/D (+) and A/D (–) groups, respectively. Improvements were observed with GLY compared to placebo in SGRQ scores, regardless of baseline A/D status; the placebo-adjusted least squares mean change from baseline in SGRQ total scores was – 3.16 (p> 0.05) and – 3.34 (p< 0.001), for the A/D (+) and A/D (–) groups, respectively. Despite numerical improvements in SGRQ scores with GLY in the A/D (+) group, a higher response to placebo was observed. GLY was generally well tolerated throughout 12 weeks of treatment; incidence of adverse events was higher in the A/D (+) group compared with the A/D (–) group in both treatment arms.Conclusion: GLY 25 μg BID resulted in numerical improvements in FEV1, SGRQ total scores and SGRQ responder rates in patients with moderate-to-very-severe COPD, regardless of A/D status at baseline; significant improvements were noted only in the A/D (+) group. The results emphasize the importance of considering underlying comorbidities including A/D when evaluating the efficacy of COPD treatments.Keywords: anxiety, COPD, depression, LAMA, nebulized glycopyrrolate

Jean Bourbeau,1 Mona Bafadhel,2 Neil C Barnes,3,4 Chris Compton,3 Valentina Di Boscio,3 David A Lipson,5,6 Paul W Jones,3,7 Neil Martin,3,8 Gudrun Weiss,3 David MG Halpin9 1Respiratory Epidemiology and Clinical Research Unit, Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 2Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK; 3Respiratory Therapy Area, GlaxoSmithKline, Brentford, Middlesex, UK; 4William Harvey Institute, Bart’s and the London School of Medicine and Dentistry, London, UK; 5Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 6Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7Institute of Infection and Immunity, St George’s, University of London, London, UK; 8University of Leicester, Leicester, UK; 9University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UKCorrespondence: Jean BourbeauMcGill University Health Centre (MUHC), 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, CanadaTel +1 514 934-1934Fax +1 514 934-8577Email jean.bourbeau@mcgill.caAbstract: Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens. International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations. Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD. Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use. We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence. Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes. Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality. These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA. Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons. Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making. We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes.Keywords: all-cause mortality, exacerbations, hospitalizations, ICS, LABA, LAMA

Luigino Calzetta,1 Angelo Coppola,2 Beatrice Ludovica Ritondo,3 Matteo Matino,3 Alfredo Chetta,1 Paola Rogliani2,3 1Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy; 2Division of Respiratory Medicine, University Hospital “Policlinico Tor Vergata”, Rome, Italy; 3Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, ItalyCorrespondence: Paola Rogliani Department of Experimental MedicineUniversity of Rome “Tor Vergata”, Via Montpellier 1, Rome 00133, ItalyTel +39 06 2090 4656Email paola.rogliani@uniroma2.itAbstract: Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.Keywords: muscarinic receptor antagonist, LAMA, tiotropium, inflammation, systematic review

Barbara P Yawn,1,2 Matthew L Mintz,3 Dennis E Doherty4 1Department of Family and Community Health, University of Minnesota, Minneapolis, MN, USA; 2COPD Foundation, Miami, FL, USA; 3Department of Medicine, George Washington University School of Medicine & Health Sciences, Washington, DC, USA; 4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kentucky, Lexington, KY, USACorrespondence: Barbara P YawnDepartment of Family and Community Health, University of Minnesota, 1963 112th Circle NE, Blaine, MN 55449, USATel +1 (507) 261 3096Email byawn47@gmail.comAbstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early detection and appropriate treatment and management of COPD can lower morbidity and perhaps mortality. Clinicians in the primary care setting provide the majority of COPD care and are pivotal in the diagnosis and management of COPD. In this review, we provide an overview of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 report, with a focus on the management of COPD in the primary care setting. We discuss the pathophysiology of COPD; describe COPD risk factors, signs, and symptoms that may facilitate earlier diagnosis of COPD; and reinforce the importance of spirometry use in establishing the diagnosis of COPD. Disease monitoring, as well as a review of the 2020 GOLD treatment recommendations, is also discussed. Patients and families are important partners in COPD management; therefore, we outline simple steps that may assist them in caring for those affected by COPD. Finally, we discuss nonpharmacological treatment options for COPD, COPD monitoring tools that may aid in the evaluation of disease progression and response to therapy, and the importance of developing a COPD action plan on an individualized basis.Keywords: COPD, LABA, LAMA, primary care

Background: Acute chemical poisoning is a significant global health problem. Chemical poisons include agrochemical, household and industrial poison subtypes. The present study used a probabilistic model based on age, gender and type of poison consumed by the patient to predict the outcome in acute suicidal poisoning cases. Material and methods: A prospective observational study was conducted at emergency department of SMS Hospital, Jaipur, India, from January 2019 to February 2020. Patients over 15 years of age with poisoning severity score 2 or above were included in the study. Probabilistic model was used to predict the outcome measured in terms of cure, death and left against medical advice (LAMA) using Minitab 14. Results: Poisoning cases were 0.32 % of all emergency presentations. Out of them, 857 (59.6 %) had consumed chemical poison. Their mean age was 32 years and men to women ratio was 1.22. Agrochemical subtype was most common followed by household and industrial poisoning. Analysis by Probabilistic model showed that person between 30-60 years is more likely to be cured and chances of death and LAMA are highest in age group 60-75. Gender-wise, men have higher possibility for recovery. Besides, a person has highest chances of recovery in case of household poisons; death is most common in industrial poisons and LAMA in agrochemical poisons. Conclusion: The study concluded that in poisoning, patients' basic information like age, gender, type of poison consumed can be used to identify high death probability and LAMA risk patients. It will assist in designing and monitoring the most effective strategies for them.

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Josuel Ora,1 Angelo Coppola,2 Mario Cazzola,3 Luigino Calzetta,4 Paola Rogliani1,3 1Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy; 2Division of Respiratory Medicine, San Filippo Neri Hospital, Rome, Italy; 3Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy; 4Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, ItalyCorrespondence: Josuel OraDivision of Respiratory Medicine, University Hospital Tor Vergata, Viale Oxford 81, Rome 00133, ItalyEmail josuel.ora@ptvonline.itIntroduction: Bronchodilators are the cornerstone of chronic obstructive pulmonary disease (COPD) therapy and long-acting muscarinic antagonists (LAMAs) as a mono or combination treatment play a pivotal role. Several LAMAs are already available on the market in different formulations, but developing a new compound with a higher M3 receptor selectivity and a lower affinity to M2 receptors to increase the therapeutic effect and minimize the adverse effects is still a goal. Moreover, new formulations could improve adherence to therapy.Areas Covered: This systematic review assesses investigational long-acting muscarinic antagonist in Phase I and II clinical trials over the last decade. It offers insights on whether LAMAs and/or their new formulations in clinical development can become effective treatments for COPD in the future.Expert Opinion: Research on LAMA seems to have come to a standstill, the few new molecules under study do not show distinctive characteristics compared to the previous ones. Muscarinic antagonist/β 2-agonist (MABAs) appear to be the major innovation currently under investigation, and they could theoretically open new research frontiers on the effect between adrenergic and muscarinic interaction in the same cell.Keywords: long-acting muscarinic antagonist, MABA, LAMA, Phase I, Phase II, efficacy, safety, COPD treatment, investigational drugs, chronic obstructive pulmonary disease

Wen-Chien Cheng,1– 6 Biing-Ru Wu,1,3,5,6 Wei-Chih Liao,1,2,4,7 Chih-Yu Chen,1 Wei-Chun Chen,1,3– 6 Te-Chun Hsia,1,4,8 Chih-Yen Tu,1– 3 Chia-Hung Chen,1,2,7 Wu-Huei Hsu1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University, Taichung, Taiwan; 3Department of Life Science, National Chung Hsing University, Taichung, Taiwan; 4Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University Hospital, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 8Department of Respiratory Therapy, China Medical University, Taichung, TaiwanCorrespondence: Chia-Hung Chen; Chih-Yu ChenDepartment of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung, TaiwanEmail hsnu758@gmail.com; cychen0808@gmail.comPurpose: Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function. Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.Patients and Methods: This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL. The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Composite CID was used in assessing the response to treatment after 24 weeks of therapy.Results: This study included 110 patients, of which 49 patients reportedly experienced CID. The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥  100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA). Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA. Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID. A baseline FEV1 of ≤ 42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.Conclusion: Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥ 100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18).Keywords: inhaled corticosteroid, ICS, long-acting muscarinic antagonist, LAMA, long-acting β2 agonist, LABA, triple therapy, chronic pulmonary obstructive disease, COPD, clinically important deterioration, CID

Background: Leaving against medical advice (LAMA) can be defined broadly as a patient’s insistence upon leaving the hospital against the treating team has expressed advice, which is both a challenge and concern for physicians, as these patients lost to follow-up, and their outcomes remain unknown. There is no previous study conducted to find the prevalence and causes of LAMA in brain tumors patients in the Middle East to the best of our knowledge. Methods: Patients studied in this research are those who were diagnosed with any type of brain tumors and were admitted to the Neurosurgical Department in Khoula Hospital (KH) but signed LAMA in the two years between January 2017 to December 2018 by going through the electronic medical records. Data obtained from the health information system includes socioeconomic characteristics, health status-related data, diagnosis-related data, and the reasons for LAMA. Results: A total number of 302 patients with brain tumors included in this study. Twenty-eight patients (9.2%) signed LAMA with a majority of those who signed LAMA were in the young adult’s group (3-39 years) and represented 18 (64%). Eight patients (28.57%) among the LAMA group and 43 patients (15.69%) in the non-LAMA group have tumors in the frontal lobe, which has found to be the most familiar location (29%). There was a significant relationship between the reason for LAMA and gender (P=0.020). Conclusion: Younger patients, male, Omani, newly diagnosed tumors, and tumors in the frontal lobe were all risk factors for LAMA. Education and awareness about LAMA recommended in order to avoid readmission and loss of follow up.

Ram Prasad Pokhrel,1 Radha Bhurtel2 1Department of Paediatrics, College of Medical Sciences Teaching Hospital, Bharatpur, Nepal; 2Department of Nursing, College of Medical Sciences Teaching Hospital, Bharatpur, NepalCorrespondence: Ram Prasad PokhrelDepartment of Paediatrics, College of Medical Sciences Teaching Hospital, Bharatpur-10, Chitwan, NepalTel +977-9801214221Email docram333@gmail.comPurpose: Discharge against medical advice (DAMA), leave against medical advice (LAMA), and self discharge have been used in similar circumstances to mean abandoning the physician’s advice and deciding to leave the hospital abruptly without caring about possible outcomes. It is a sensitive issue common in NICUs across the developing world. To decrease NMR and under-5 mortality further, it is important to explore the factors leading to DAMA. Hence, this study aims to find the prevalence of DAMA, its causes, and related socio-demographic factors.Patients and Methods: A cross-sectional descriptive study was conducted in the NICU of College of Medical Sciences Teaching Hospital located in central Nepal from June 2019 to May 2020. Out of 110 cases of DAMA during the study period, 105 cases gave consent to participate in the study. Medical data were recorded from patient records followed by filling out of a semi-structured questionnaire by parents of the patients.Results: Out of 611 cases admitted to the NICU during the study period, 110 neonates (18%) were self-discharged. The leading cause for parents to take such a decision was poor financial condition (58%), followed by lack of improvement (21%).Conclusion: The study showed that DAMA in the NICU was 18%. Poor financial condition followed by lack of improvement in patient’s condition were the main reasons for self-discharge.Keywords: LAMA, DAMA, self-discharge, NICU

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) created an ABCD tool to assess staging and severity of COPD subgroups that respond to LAMA or LABA with improved quality of life and reduced exacerbations. Our study assesses perception of physicians at five community hospitals towards LAMA use for patients admitted with COPD exacerbations according to the GOLD guidelines and describes the experience at our hospital. Methods: Electronic survey forms regarding LAMA use and the GOLD criteria ABCD for COPD treating physicians were sent to five hospitals. A one-year chart review at our hospital determined prevalent use of a maintenance LAMA or LABA inhaler in patients admitted with acute COPD exacerbation. Currently, our EMR does not require a field for the GOLD ABCD categorization. Results: We obtained a 33% (45/136) response rate. Of these, 63% felt a LAMA to be essential on formulary; 60% were neutral or unlikely to initiate LAMA on admission; 47.7% likely or very likely to start a LAMA during hospitalization; 82% were neutral to very likely to discharge a patient on a LAMA if deemed necessary for maintenance. Of those admitted for acute COPD exacerbations to our hospital, over a third of COPD patients were not on a maintenance LAMA or LABA. Conclusions: Most physicians felt it important to prescribe a maintenance LAMA to COPD patients hospitalized for acute exacerbation. Our hospital’s use of LAMA or LABA demonstrates the need to incorporate strategies to encourage appropriate prescribing of these LA inhalers per GOLD guidelines.

Jill A Ohar,1 Ayca Ozol-Godfrey,2 Thomas Goodin,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest University, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Jill A OharDepartment of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1054, USATel +1 336 716 7765Email johar@wakehealth.eduPurpose: The clinical manifestation of COPD can differ by gender, with women experiencing worse lung function and health-related quality of life than men. Additionally, women tend to report more symptoms given the same disease severity. Accordingly, the impact of gender on efficacy and safety in patients with moderate-to-very-severe COPD was examined following 12 weeks of nebulized glycopyrrolate (GLY) 25 μg twice daily (BID) or placebo.Patients and Methods: GLY and placebo pooled data from the replicate 12-week GOLDEN 3 and 4 studies (n=861) were grouped by gender. Endpoints reported were change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total scores. Safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs.Results: Men (placebo: 54.7%; GLY: 56.1%) were generally older with a greater proportion of high cardiovascular risk and use of background long-acting β2-agonists or inhaled corticosteroids. GLY treatment resulted in significant, clinically important improvements in trough FEV1, regardless of gender. Patients treated with GLY reported significant improvements in SGRQ total score, irrespective of gender; however, the improvement was numerically higher in women. Although EXACT-RS improved in both genders, only women experienced a significant improvement. Overall, GLY was well tolerated with a numerically lower incidence of AEs in men than women.Conclusion: Treatment with nebulized GLY resulted in lung function, SGRQ total score, and EXACT-RS total score improvements regardless of gender. However, only EXACT-RS showed significantly greater improvements in women compared with men. Treatment with GLY was generally well tolerated across genders. These data support the efficacy and safety of GLY 25 μg BID in patients with moderate-to-very-severe COPD, independent of gender. Gender similarities in airflow improvement and differences in symptom-reporting augment the evidence supporting the consideration of individualized treatment plans for COPD patients.Keywords: COPD, gender, LAMA, nebulized glycopyrrolate