Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial

Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n = 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n = 34/73) experienced respiratory TEAEs, and 27.4% (n = 20) had serious TEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% (n = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600)

Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases

Management of drug toxicity in M. avium complex pulmonary disease - an expert panel survey

Adverse events are frequent in NTM pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus and GI upset. These opinions can provide assistance in individual patient management decisions

One-Year outcomes and health care utilization in survivors of severe acute respiratory syndrome

Background Severe Acute Respiratory Syndrome (SARS) became a global epidemic in 2003. Comprehensive information on 1-year outcomes and health care utilization is lacking. Research conducted during the SARS outbreak may help inform research planning for future public health emergencies. The objective of this study was to evaluate the 1-year outcomes in survivors of SARS and their family caregivers. Method The study was prospective and observational. We evaluated 117 SARS survivors from Toronto, Ontario. Patients were interviewed and underwent physical examination, pulmonary function testing, chest radiography, a 6-minute-walk test, quality-of-life measures, and self-report of health care utilization. At 1 year, informal caregivers were identified for a survey on caregiver burden. Results The enrolled survivors of SARS were young (median age, 42 years), and most were women (67%) and health care workers (65%). At 1 year after hospital discharge, pulmonary function measures were in the normal range, but 18% of patients had a significant reduction in distance walked in 6 minutes. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domains were 0.3 to 1.0 SD below normal at 1 year. Of the patients, 17% had not returned to work by 1 year. Fifty-one patients required 668 visits to psychiatry or psychology practitioners. During the SARS epidemic, informal caregivers reported a decline of 1.6 SD below normal on the mental component score of the SF-36. Conclusions Most SARS survivors had good physical recovery from their illness, but some patients and their caregivers reported a significant reduction in mental health 1 year later. Strategies to ameliorate the psychological burden of an epidemic on the patient and family caregiver should be considered as part of future pandemic planning. Severe acute respiratory syndrome (SARS) became a global epidemic in 2003. Most cases were in Asia, and the largest concentration of North American cases occurred in Toronto, Ontario.1 Research efforts during and after the epidemic focused on the epidemiologic features of the illness,1- 2 the detailed characterization of the pathogen,3- 4 the clinical course,5- 10 and the short-term outcomes of the acute disease.11 The longer-term physical and psychological consequences of SARS were not reported until recently. Several investigations of these longer-term outcomes (>6 months) have focused on pulmonary function,12- 14 distance walked in 6 minutes,12 and health-related quality of life (QOL).12- 13 To date, in patients with SARS, there is little information on the pattern of return to work, exercise tolerance, or health care utilization after the SARS episode. Also, there have been no reports to our knowledge on the impact of this acute illness on the family caregiver. The goals of this study were to conduct a comprehensive and family-centered evaluation of the 1-year outcomes in survivors of SARS and their family caregivers

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: A NTM-NET collaborative study.

International audienceA significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide.To provide a snapshot of NTM species distribution, global partners in the NTM-NET framework (www.ntm-net.org), a branch of TBNET, provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualized the relative distribution of the different NTM found per continent and country.We received species identification data for 20182 patients, from 62 laboratories in 30 countries across six continents. Ninety-one different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii, and rapid growing mycobacteria were observed.This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differs by countries within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location

Technical design report for the upgrade of the ALICE inner tracking system

ALICE (A Large Ion Collider Experiment) is studying the physics of strongly interacting matter, and in particular the properties of the Quark-Gluon Plasma (QGP), using proton-proton, proton-nucleus and nucleus-nucleus collisions at the CERN LHC (Large Hadron Collider). The ALICE Collaboration is preparing a major upgrade of the experimental apparatus, planned for installation in the second long LHC shutdown in the years 2018-2019. A key element of the ALICE upgrade is the construction of a new, ultra-light, high-resolution Inner Tracking System (ITS) based on monolithic CMOS pixel detectors. The primary focus of the ITS upgrade is on improving the performance for detection of heavy-flavour hadrons, and of thermal photons and low-mass di-electrons emitted by the QGP. With respect to the current detector, the new Inner Tracking System will significantly enhance the determination of the distance of closest approach to the primary vertex, the tracking efficiency at low transverse momenta, and the read-out rate capabilities. This will be obtained by seven concentric detector layers based on a 50 \uce\ubcm thick CMOS pixel sensor with a pixel pitch of about 30\uc3\u9730 \uce\ubcm2. This document, submitted to the LHCC (LHC experiments Committee) in September 2013, presents the design goals, a summary of the R&D activities, with focus on the technical implementation of the main detector components, and the projected detector and physics performance. \uc2\ua9 2014 CERN on behalf of The ALICE Collaboration