Hamburg Südamerikanische Dampfschifffahrts-Gesellschaft A/S & Co KG, widely known as Hamburg Süd, is a German container shipping company. Founded in 1871, Hamburg Süd is among the market leaders in the North–South trade. It also serves all significant East–West trade lanes.The shipping entity was formerly part of the Oetker Group, but was sold to A.P. Moller–Maersk Group's shipping division Maersk Line in 2017.
OBJECTIVE:The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with descending thoracic and thoraco-abdominal aortic pathologies, in succession to the 2017 version, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS:The guidelines are based on scientific evidence complemented with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to the ESVS grading system, where the strength (class) of each recommendation is graded from I to III and the level of evidence from A to C. RESULTS:One hundred and twenty-nine recommendations have been issued across the following main topics: (1) acute thoracic aortic syndrome; (2) chronic type B aortic dissection; (3) descending thoracic and thoraco-abdominal aortic aneurysms; (4) ruptured descending thoracic and thoraco-abdominal aortic aneurysms; and (5) blunt thoracic aortic injury. Additional topics include genetic aortopathy, floating thrombus and shaggy aorta, inflammatory aortitis, mycotic aortic aneurysms, coarctation of the aorta, aberrant subclavian artery, and service standards such as surgical volume, imaging, risk assessment, and optimisation. Special considerations include pregnancy, left subclavian artery revascularisation, spinal cord ischaemia, stroke prevention, vascular access, and the patient's perspective. A final chapter addresses unresolved issues. CONCLUSION:These clinical practice guidelines provide comprehensive, up to date advice to clinicians and patients on the management of descending thoracic and thoraco-abdominal aortic pathologies.
BACKGROUND:Obstructive sleep apnoea (OSA) is highly prevalent but approved pharmacological treatment options are missing. Sultiame improves the ventilatory response and upper airway muscle activity by inhibiting carbonic anhydrase. This study aimed to prospectively assess the efficacy and safety of three dosages of sultiame in OSA. METHODS:This multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was performed at 28 hospitals and community-based sites in five European countries. Adults (aged 18-75 years) with untreated, moderate to severe OSA and an Apnoea-Hypopnea Index (AHI) of ≥15 to ≤50 events per h were randomly assigned (1:1:1:1), using interactive response technology, to receive placebo or sultiame 100 mg, 200 mg, or 300 mg tablets of identical appearance once per day at bedtime for 15 weeks. Randomisation was stratified by baseline AHI3a. The primary outcome measure for efficacy was the relative change of AHI3a from baseline to week 15 (scheduled treatment end). All participants who were randomly assigned were included in the primary efficacy analysis using an estimands framework and in the safety analysis. This trial is registered with EudraCT (2021-002926-26) and ClinicalTrials.gov (NCT05236842) and is complete. FINDINGS:Between Dec 2, 2021, and April 8, 2023, 535 patients were screened and 298 were randomly assigned to placebo (n=75), or sultiame 100 mg (n=74), 200 mg (n=74), or 300 mg (n=75). 240 patients completed 15 weeks of treatment. 220 (74%) of 298 participants were male and 78 (26%) were female. In the full analysis set, placebo-subtracted relative AHI3a adjusted means change at week 15 was -16·4% (95% CI -31·3 to -1·4; p=0·032), -30·2% (-45·4 to -15·1; p<0·0001), and 34·6% (-49·1 to -20·0; p<0·0001) for sultiame 100 mg, 200 mg, and 300 mg, respectively. The incidence of adverse events increased dose-dependently: 46 (61%) of 75 patients in the placebo group, 54 (73%) of 74 in the 100 mg group, 62 (84%) of 74 in the 200 mg group, and 68 (91%) of 75 in the 300 mg group. Events reported in more than 10% of patients in the placebo, 100 mg, 200 mg, or 300 mg groups were paraesthesia (seven [9%] of 75, 16 [22%] of 74, 32 [43%] of 74, 43 [57%] of 75), headache (six [8%], five [7%], 12 [16%], 11 [15%]), COVID-19 (three [4%], three [4%], six [8%], ten [13%]), and nasopharyngitis (nine [12%], three [4%], seven [9%], seven [9%]). INTERPRETATION:Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness. These findings offer perspectives for a pharmaceutical approach to treatment of patients with obstructive sleep apnoea. FUNDING:Desitin Arzneimittel.
