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Context: Breathlessness is a cardinal symptom in cardiorespiratory disease and consists of multiple dimensions that can be measured using the instruments Dyspnea-12 (D12) and the Multidimensional Dyspnea Profile (MDP).Objectives: The objective of the study is to determine the minimal clinically important differences (MCIDs) of all D12 and MDP summary and subdomain scores as well as the instruments' feasibility in patients with cardiorespiratory disease.Methods: Prospective multicenter cohort study of outpatients with diagnosed cardiorespiratory disease and breathlessness in daily life. D12 and MDP were assessed at baseline, after 30-90 minutes and two weeks. MCIDs were calculated using anchor-based and distributional methods for summary and subdomain scores. Feasibility was assessed as rate of missing data, help required, self-reported difficulty, and completion time.Results: A total 182 outpatients (53.3% women) were included; main diagnoses were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%), and idiopathic pulmonary fibrosis (19%). Anchor-based MCIDs were for D12 total score 2.83 (95% CI 1.99-3.66); D12 physical 1.81 (1.29-2.34); D12 affective 1.07 (0.64-1.49); MDP A1 unpleasantness 0.82 (0.56-1.08); MDP perception 4.63 (3.21-6.05), and MDP emotional score 2.37 (1.10-3.64). The estimates were consistent with small-to-moderate effect sizes using distributional analysis, and MCIDs were similar between COPD and non-COPD patients. The instruments were generally feasible and quick to use.Conclusion: D12 and MDP are responsive to change and feasible for use for assessing multidimensional breathlessness in outpatients with cardiorespiratory disease. MCIDs were determined for use as endpoints in clinical trials. [ABSTRACT FROM AUTHOR]

Exhaust Gas Cleaning Systems (EGCS), operating in open-loop mode, continuously release acidic effluents (scrubber waters) to marine waters. Furthermore, scrubber waters contain high concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and alkylated PAHs, potentially affecting the plankton in the receiving waters. Toxicity tests evidenced significant impairments in planktonic indicators after acute, early-life stage, and long-term exposures to scrubber water produced by a vessel operating with high sulphur fuel. Acute effects on bacterial bioluminescence (Aliivibrio fischeri), algal growth (Phaeodactylum tricornutum, Dunaliella tertiolecta), and copepod survival (Acartia tonsa) were evident at 10 % and 20 % scrubber water, while larval development in mussels (Mytilus galloprovincialis) showed a 50 % reduction at ∼5 % scrubber water. Conversely, larval development and reproductive success of A. tonsa were severely affected at scrubber water concentrations ≤1.1 %, indicating the risk of severe impacts on copepod populations which in turn may result in impairment of the whole food web., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Picone reports financial support was provided by European Union., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Marine environmental risk assessments rarely consider the cumulative risk from multiple contaminants and sources. Ships give rise to a range of contaminants, originating from different onboard sources, resulting in contaminant loads to the marine environment. Here, the Ship Traffic Emission Assessment Model (STEAM), in combination with the hydrodynamic and chemical fate model MAMPEC, was used to calculate loads and predicted environmental concentrations (PECs) of metals and polycyclic aromatic hydrocarbons, in four ports. PECs were compared to the predicted no effect concentrations (PNEC) to assess environmental risk from the different onboard sources, both separately and cumulatively. The results show that three out of four ports were subject to unacceptable risk. This study highlights the importance of accounting for multiple contaminant sources when assessing the marine environmental risks of shipping and challenges the suitability of the proposed new international guidelines on how to assess risk of scrubber water discharge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Baltic Sea is a sensitive environment that is affected by chemical pollution derived from multiple natural and anthropogenic sources. The overall aim of this study was to estimate the load of metals and polycyclic aromatic hydrocarbons (PAHs) from shipping and leisure boating, relative other sources, to the Baltic Sea and to identify possible measures that could lead to major reductions in the loads of hazardous substances from maritime shipping and leisure boating. The use of copper-based antifouling paints, and operation of scrubbers in open loop mode, were the two most dominant identified sources of hazardous substances to the Baltic Sea. Open loop scrubbers accounted for 8.5 % of the total input of anthracene to the sea. More than a third of the total load of copper can be reduced if copper-free antifouling paints or other biocide-free antifouling strategies are used on ships and leisure boats., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease., Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure., Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes., Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes., Competing Interests: Conflict of interest: No conflicts of interest exist for the authors., (Copyright ©The authors 2022.)

Objective: Long-term oxygen therapy (LTOT) during 15 h/day or more prolongs survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the net effects (benefits or harms) from LTOT 24 h/day compared with 15 h/day or the effect in conditions other than COPD. We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) of LTOT prescribed 24 h/day compared with 15 h/day. The primary endpoint is all-cause-mortality at 1 year. Secondary endpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes in interstitial lung disease., Methods/design: Patients qualifying for LTOT are randomized to LTOT 24 h/day versus 15 h/day during 12 months using the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126 randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality, hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12 months., Discussion: The R-RCT approach combines the advantages of a prospective randomized trial and large clinical national registries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT., Trial Registration: Clinical Trial registered with www.clinicaltrials.gov , Title: REgistry-based Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

Background: The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA., Objective: To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective., Patients and Methods: In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy., Results: Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively)., Limitations: The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive., Conclusion: In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude., Trial Registration: Registered with ClinicalTrials.gov (#NCT02148510).

Shigella spp. are the causative agents of bacillary dysentery, leading to extensive mortality and morbidity worldwide. These facultative intracellular bacteria invade the epithelium of the colon and the rectum, inducing a severe inflammatory response from which the symptoms of the disease originate. Shigella are human pathogens able to manipulate and subvert the innate immune system surveillance. Shigella dampens inflammasome activation in epithelial cells. In infected macrophages, inflammasome activation and IL-1β and IL-18 release lead to massive neutrophil recruitment and greatly contribute to inflammation. Here, we describe how Shigella hijacks and finely tunes inflammasome activation in the different cell populations involved in pathogenesis: epithelial cells, macrophages, neutrophils, DCs, and B and T lymphocytes. Shigella emerges as a "sly" pathogen that switches on/off the inflammasome mechanisms in order to optimize the interaction with the host and establish a successful infection.

Objective: To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD)., Design: Population based longitudinal consecutive cohort study., Setting: Centres prescribing long term oxygen therapy in Sweden., Patients: 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register., Main Outcome Measures: Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs., Results: 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤ 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia., Conclusions: Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.