Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: results of PROMIS-I and PROMIS-II, two randomised, double-blind, placebo-controlled phase 3 trials assessing safety and efficacy over 12 months.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is associated with increased exacerbations and mortality in people with bronchiectasis. The PROMIS-I and PROMIS-II trials investigated the efficacy and safety of 12-months of inhaled colistimethate sodium delivered via the I-neb. METHODS: Two randomised, double-blind, placebo-controlled trials of twice per day colistimethate sodium versus placebo were conducted in patients with bronchiectasis with P aeruginosa and a history of at least two exacerbations requiring oral antibiotics or one requiring intravenous antibiotics in the previous year in hospitals in Argentina, Australia, Belgium, Canada, France, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Spain, Switzerland, the UK, and the USA. Randomisation was conducted through an interactive web response system and stratified by site and long term use of macrolides. Masking was achieved by providing colistimethate sodium and placebo in identical vials. After random assignment, study visits were scheduled for 1, 3, 6, 9, and 12 months (the end of the treatment period); and telephone calls were scheduled for 7 days after random assignment and 2 weeks after the end of treatment. The primary endpoint was the mean annual exacerbation rate. These trials are registered with EudraCT: number 2015-002743-33 (for PROMIS-I) and 2016-004558-13 (for PROMIS-II), and are now completed. FINDINGS: 377 patients were randomly assigned in PROMIS-I (177 to colistimethate sodium and 200 to placebo; in the modified intention-to-treat population, 176 were in the colistimethate sodium group and 197 were in the placebo group) between June 6, 2017, and April 8, 2020. The annual exacerbation rate was 0·58 in the colistimethate sodium group versus 0·95 in the placebo group (rate ratio 0·61; 95% CI 0·46-0·82; p=0·0010). 287 patients were randomly assigned in PROMIS-II (152 were assigned to colistimethate sodium and 135 were assigned to placebo, in the modified intention-to-treat population), between Feb 12, 2018, and Oct 22, 2021. PROMIS-II was then prematurely terminated due to the effect of the COVID-19 pandemic. No significant difference was observed in the annual exacerbation rate between the colistimethate sodium and placebo groups (0·89 vs 0·89; rate ratio 1·00; 95% CI 0·75-1·35; p=0·98). No major safety issues were identified. The overall frequency of adverse events was 142 (81%) patients in the colistimethate sodium group versus 159 (81%) patients in the placebo group in PROMIS-I, and 123 (81%) patients versus 104 (77%) patients in PROMIS-II. There were no deaths related to study treatment. INTERPRETATION: The data from PROMIS-I suggest a clinically important benefit of colistimethate sodium delivered via the I-neb adaptive aerosol delivery system in patients with bronchiectasis and P aeruginosa infection. These results were not replicated in PROMIS-II, which was affected by the COVID-19 pandemic and prematurely terminated. FUNDING: Zambon.

Policies and Toxicological Screenings for No Drug Addiction: An Example from the Civil Aviation Workforce.

INTRODUCTION: Since 2008, Italian legislators, with the aim of ensuring public safety, have made it mandatory for an occupational doctor (OD) to assess specific categories of workers to exclude those who may have consumed drugs of abuse. Due to the relevance of work activities relating to the civil aviation and airport sector, a policy based on the use of training and information tools, as well as a health surveillance protocol, has been undertaken since 2009. MATERIALS AND METHODS: A total of 61,008 workers at a commercial airline underwent health surveillance between 2009 and 2019. Following ≤24 h notification, their urine was screened for opiates, cocaine, cannabinoids, amphetamines, methamphetamines, and methylenedioxymethamphetamine (MDMA) using an immunochemical test. Positive results were confirmed using Gas Chromatography-Mass Spectrometry (GC/MS) or Liquid Chromatography -Mass Spectrometry (LC/MS). In confirmed cases, the workers were declared unfit and sent to a specialized laboratory for a second level analysis. RESULTS: Positive results, initially >1%, have halved in the last four years (<0.5%). The percentage of positive results was consistently very low among pilots and, moreover, the rare positive cases detected were due to a cross-reactivity phenomena. The highest and most discontinuous percentages seen occurred in the population undergoing a pre-employment examination. Regarding the types of substance used, a prevalence of cannabis (58.52%) and cocaine (35.2%) use was observed. CONCLUSIONS: The data presented indicate that the air transport sector, in all its components (ground workers and air crews), has a very limited number of substance abusers, and this number tends to decrease over time and with work seniority. Another aspect of particular interest, and which is more specific to toxicology, concerns the detection of cross-reactivity in urinary immunochemical screening between the antibodies to drugs of abuse and certain other drugs, such as anti-inflammatories or antibiotics; as well as foods, and other commonly used substances.

Legionella and Air Transport: A Study of Environmental Contamination.

Introduction: There is growing interest in the public health and transport sectors in research into exposure to biological hazards, considering not only the risks arising from inter-human contagion, but also those related to exposure to the flight environment itself. The aim of this paper is to report data from an investigation into the water and air-conditioning systems of commercial aircraft for the presence of Legionella contamination, with a total of 645 water samples taken during the period 2007−2021. Methods: The investigation involved 126 aircraft of six different commercial aircraft types: MD80, Airbus A320 F, Embraer 175/190, AIRBUS A330, Boeing 767 and Boeing 777. Water samples were taken from the water systems (toilet taps, galley and boilers). Each sample was preliminarily subjected to an evaluation of the following parameters: temperature, pH and residual chlorine. The ScanVit® Legionella kit was used for bacteria detection and enumeration. Results: Samples were considered positive if the number of colony-forming units/liter (CFU/L) was >100. For the entire observation period, 45% of the investigated aircraft tested positive. Regarding the overall number of samples analyzed, 68.4% (441/645) were below 100 CFU/L, and thus within the limits allowed by the Italian Guidelines. Conclusions: Water system contamination with Legionella in the air transport field is a real public health issue that should not be underestimated given the heavy passenger traffic. Infection should be considered an occupational risk to which crew members are exposed.

Long-term Efficacy of Safinamide on Parkinson's Disease Chronic Pain.

INTRODUCTION: Chronic pain is an important yet overlooked non-motor symptom of Parkinson's disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms. OBJECTIVES: To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment. METHODS: This is a post hoc analysis of the data from the 2-year study 018, focused on the reduction of concomitant pain treatments and on the scores of pain-related items of the Parkinson's disease quality of life questionnaire (PDQ-39). RESULTS: Safinamide, compared with placebo, significantly improved the PDQ-39 items 37 ("painful cramps or spasm," p = 0.0074) and 39 ("unpleasantly hot or cold," p = 0.0209) and significantly reduced the number of concomitant pain treatments by 26.2% (p = 0.005). A significantly greater proportion of patients in the safinamide group was not using pain drugs after 2 years of treatment (p = 0.0478). CONCLUSIONS: The positive effects of safinamide on PD chronic pain were maintained in the long term. Further investigations are desirable to confirm their clinical relevance. FUNDING: Zambon SpA.

Diabetes mellitus en relación con tratamiento con interferón / Diabetes mellitus during interferon therapy

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Arteritis de células gigantes con nódulos pulmonares / Giant cell arteritis with pulmonary nodules

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