Liver injury after ischemia was significantly aggravated by hyperoxia as a consequence of immune cell-mediated oxidative burst. Further studies are needed to elucidate whether routine delivery of high inspirational oxygen concentrations postoperatively should be limited.
Introduction Acute mountain sickness (AMS) may develop in nonacclimatized individuals after exposure to altitudes ≥2500 m. Anecdotal reports suggest that endurance-trained (ET) athletes with a high maximal oxygen uptake (V˙O2max) may be at increased risk for AMS. Possible underlying mechanisms include a training-induced increase in resting parasympathetic activity, higher resting metabolic rate (RMR), and lower hypoxic ventilatory response (HVR). Methods In 38 healthy, nonacclimatized men (19 ET and 19 untrained controls [UT], V˙O2max 66 ± 6 mL·min−1·kg−1 vs 45 ± 7 mL·min−1·kg−1; P < 0.001) peripheral oxygen saturation (SpO2), heart rate variability, RMR, and poikilocapnic HVR were assessed at 424 m and during 48 h at 3450 m after passive ascent by train (~2 h). Acute mountain sickness was evaluated by AMS cerebral (AMS-C) score. Results On day 1 at altitude, ET presented with a higher AMS incidence (42% vs 11%; P < 0.05) and severity (AMS-C score: ET, 0.48 ± 0.5 vs UT, 0.21 ± 0.2; P = 0.03), but no group difference was found on days 2 and 3. SpO2 decreased upon arrival at altitude (ET: 82% ± 6% vs UT: 83% ± 4%; p time <0.001) with a significantly different time course between ET and UT (p time × group = 0.045). Parasympathetic activity decreased at altitude (P < 0.001) but was always higher in ET (P < 0.05). At altitude RMR increased (P < 0.001) and was higher in ET (P < 0.001). Hypoxic ventilatory response increased only in ET (P < 0.05) and was greater than in UT after 24 and 48 h (P < 0.05). Conclusions Endurance-trained athletes are at higher risk for developing AMS on the first day after passive and rapid ascent to 3450 m, possibly due to an increased parasympathetic activity and an increased RMR, while HVR appeared to be of minor importance. Differences in AMS time course and physiological responses should be taken into consideration when ET are planning high-altitude sojourns.
EGFR, epidermal growth factor receptor; mNSCLC, metastatic non-small cell lung cancer. BRIEF SUMMARY OFPRESCRIBING INFORMATION EXKIVITY ™ (MOBOCERTINIB) WARNING: QTc PROLONGATION and TORSADES DE POINTES • EXKIVITY can cause life-threatening heart rate-corrected QT (QTc) prolongation,including Torsades de Pointes, which can be fatal, and requires monitoring of QTc and electrolytes at baseline and periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation [see Warnings and Precautions (5.1)]. • Avoid use of concomitant drugs which are known to prolong the QTc interval and use of strong or moderate CYP3A inhibitors with EXKIVITY, which may further prolong the QTc [see Warnings and Precautions (5.1), Drug Interactions (7.1, 7.3)]. • Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of QTc prolongation [see Dosage and Administration (2.3)]. 1 INDICATIONS AND USAGE EXKIVITY is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1)], whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 2 DOSAGE AND ADMINISTRATION 2.1 Patient Selection Select patients with locally advanced or metastatic NSCLC for treatment with EXKIVITY based on the presence of EGFR exon 20 insertion mutations [see Clinical Studies (14)]. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of EXKIVITY is 160 mg orally once daily until disease progression or unacceptable toxicity. Take EXKIVITY with or without food [see Clinical Pharmacology 12.3], at the same time each day. Swallow EXKIVITY capsules whole. Do not open, chew or dissolve the contents of the capsules.If a dose is missed by more than 6 hours, skip the dose and take the next dose the following day at its regularly scheduled time.If a dose is vomited, do not take an additional dose. Take the next dose as prescribed the following day. Dosage Modifications for Adverse ReactionsEXKIVITY dose reduction levels for adverse reactions are summarized in Table 1. USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], EXKIVITY can cause fetal harm when administered to a pregnant woman. There are no available data on EXKIVITY use in pregnant women. Oral administration of mobocertinib to pregnant rats during the period of organogenesis resulted in embryolethality (embryo-fetal death) and maternal toxicity at plasma exposures approximately 1.7 ...
The value of psychotherapy in surgical patients suffering from postoperative delirium is unclear. Options for the treatment of established postoperative delirium are few; therapy largely relies on the avoidance of postoperative delirium facilitating factors, like specific drugs and environmental factors in the perioperative setting. Established medical therapies’ efficacy in terms of decreasing incidence of postoperative delirium is very low. The aim of this project is to suggest new therapeutic options in the form of cognitive behavioural therapy as a possible preventive and psychotherapeutic treatment of postoperative delirium. Life expectancy in developed countries increases worldwide and both the need for surgical treatment and the probability of postoperative delirium occurrence increase with age. Due to the necessity of addressing the individual’s negative consequences of postoperative delirium and to optimise socioeconomical needs, new therapeutic options for the treatment of postoperative delirium are desperately needed.
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