Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements. Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries. Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001). Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.

Resveratrol treatment does not reduce arterial inflammation in males at risk of type 2 diabetes: a randomized crossover trial

Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Results Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6–1.7)) in comparison to placebo treatment (1.5 (1.4–1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Conclusions Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.

Efficacy of ibuprofen gargle for postoperative pain after mandibular third molar extraction: a phase II, placebo-controlled, double-blind, randomized crossover trial (Preprint)

BACKGROUND Extraction of mandibular third molars is one of the most commonly performed oral surgical procedures, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management. Oral administration of NSAIDs can produce various adverse events such as gastrointestinal disorders, renal and hepatic dysfunction, and platelet dysfunction. Topical use of analgesics has been proposed as an alternative to oral and injectable medications to safely improve postoperative pain relief. We will conduct a single-center, placebo-controlled, double-blind, randomized crossover trial to assess the pain-relieving effect of an ibuprofen-containing gargle in patients undergoing extraction of mandibular third molars in comparison with a placebo gargle. OBJECTIVE This will be the first clinical study to evaluate the efficacy of ibuprofen gargle for relieving postoperative pain after extraction of mandibular third molars. METHODS This study will be performed at Kobe University Hospital. Participants (n = 40) will be randomized equally to one of two groups. The IP group will receive ibuprofen gargle on postoperative day (POD) 1 and placebo gargle on POD 2. The PI group will receive placebo gargle on POD 1 and ibuprofen gargle on POD 2. Both groups will receive ibuprofen gargle on PODs 3 to 5 at least once daily. The primary objective is to estimate the within-subject difference in a visual analogue scale (VAS) before and 5 minutes after use of ibuprofen or placebo gargle on PODs 1 and 2. The secondary objectives are to estimate the within-subject difference in ΔVAS before and 15 minutes after use of ibuprofen or placebo gargle on PODs 1 and 2, the ΔVAS before and after 5 or 15 minutes of use of ibuprofen gargle on PODs 3 to 5, the overall effectiveness (self-completion, five scales) on PODs 1 to 5, the daily frequency of use (ibuprofen or placebo gargle and analgesics) on PODs 1 to 7, and the occurrence of adverse events. RESULTS The Kobe university Certified Review Board approved the study. The intervention was implemented in May 2021. CONCLUSIONS This trial will provide exploratory evidence of the efficacy and safety of ibuprofen gargle for pain reduction after mandibular third molar extraction. CLINICALTRIAL Japan Registry of Clinical Trials (jRCT) identifier: jRCTs051210022. Registered on 10 May 2021.

Direct vs. Video-Laryngoscopy for Intubation by Paramedics of Simulated COVID-19 Patients under Cardiopulmonary Resuscitation: A Randomized Crossover Trial

A safe way of securing the airway with an endotracheal tube is one of the priorities of an advanced cardiovascular life support algorithm for suspected or confirmed COVID-19 patients. The aim of this study was to compare intubation success rates (ISR) and intubation time (IT) of different laryngoscopes for simulated COVID-19 patients under cardiopulmonary resuscitation. The study was designed as a prospective, randomized, crossover trial. Fifty four active paramedics performed endotracheal intubation with a Macintosh direct laryngoscope (MAC) and McGrath videolaryngoscope (McGrath) with and without personal protective equipment (PPE). Without PPE, ISRs were 87% and 98% for MAC and McGrath, respectively (p = 0.32). ITs were 22.5 s (IQR: 19–26) and 19.5 s (IQR: 17–21) for MAC and McGrath, respectively (p = 0.005). With PPE, first-pass ISR were 30% and 89% with MAC and McGrath, respectively (p < 0.001). The overall success rates were 83% vs. 100% (p = 0.002). Median ITs were 34.0 s (IQR: 29.5–38.5) and 24.8 s (IQR: 21–29) for MAC and McGrath, respectively (p < 0.001). In conclusion, the McGrath videolaryngoscope appears to possess significant advantages over the Macintosh direct laryngoscope when used by paramedics in suspected or confirmed COVID-19 intubation scenarios.