Edoxaban and/or colchicine in outpatients with COVID-19: rationale and design of the CONVINCE trial.

BACKGROUND: An excessive inflammatory response and a hypercoagulable state are not infrequent in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse clinical outcomes. However, the optimal treatment strategy for COVID-19 patients managed in the out-of-hospital setting is still uncertain. DESIGN: The CONVINCE (NCT04516941) is an investigator-initiated, open-label, blinded-endpoint, 2 × 2 factorial design randomized trial aimed at assessing two independently tested hypotheses (anticoagulation and anti-inflammatory ones) in COVID-19 patients. Adult symptomatic patients (≥18 years of age) within 7 days from reverse transcription-PCR (RT-PCR) diagnosis of SARS-CoV-2 infection managed at home or in nursery settings were considered for eligibility. Eligible patients fulfilling all inclusion and no exclusion criteria were randomized to edoxaban versus no treatment (anticoagulation hypothesis) and colchicine versus no treatment (anti-inflammatory hypothesis) in a 1 : 1:1 : 1 ratio. The study had two co-primary endpoints (one for each randomization), including the composite of major vascular thrombotic events at 25 ±â€Š3 days for the anticoagulation hypothesis and the composite of SARS-CoV-2 detection rates at 14 ±â€Š3 days by RT-PCR or freedom from death or hospitalizations (anti-inflammatory hypothesis). Study endpoints will be adjudicated by a blinded Clinical Events Committee. With a final sample size of 420 patients, this study projects an 80% power for each of the two primary endpoints appraised separately. CONCLUSION: The CONVINCE trial aims at determining whether targeting anticoagulation and/or anti-inflammatory pathways may confer benefit in COVID-19 patients managed in the out-of-hospital setting. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04516941.

S2k guideline for diving accidents.

For the purposes of this guideline, a diving accident is defined as an event that is either potentially life-threatening or hazardous to health as a result of a reduction in ambient pressure while diving or in other hyperbaric atmospheres with and without diving equipment. This national consensus-based guideline (development grade S2k) presents the current state of knowledge and recommendations on the diagnosis and treatment of diving accident victims. The treatment of a breath-hold diver as well as children and adolescents does not differ in principle. In this regard only unusual tiredness and itching without visible skin changes are mild symptoms. The key action statements: on-site 100% oxygen first aid treatment, immobilization/no unnecessary movement, fluid administration and telephone consultation with a diving medicine specialist are recommended. Hyperbaric oxygen therapy (HBOT) remains unchanged as the established treatment in severe cases, as there are no therapeutic alternatives. The basic treatment scheme recommended for diving accidents is hyperbaric oxygenation at 280 kPa.

A randomised, non-inferiority study of chloroprocaine 2% and ropivacaine 0.75% in ultrasound-guided axillary block.

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI - 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155-170] min for chloroprocaine versus 380 [209-450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile.Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria-BASG).

Inflammation reduces osteoblast cytotoxicity induced by diclofenac: An in vitro study.

BACKGROUND: Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN: Laboratory in vitro study. SETTING: Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human osteoblasts. INTERVENTIONS: Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION: Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenac cytotoxicity, especially in the presence of higher concentration and longer exposure time.

Spinal 1% 2-Chloroprocaine versus general anesthesia for ultra-short outpatient procedures: a retrospective analysis.

INTRODUCTION: 2-Chloroprocaine is a local anesthetic with a very short half-life and a favorable evolution of spinal block for ultra-short outpatient procedures. The aim of this retrospective study is to evaluate the clinical impact of the introduction of spinal 1% 2-chloroprocaine compared to general anesthesia at the ARS Medica Clinic (Switzerland). MATERIAL AND METHOD: We retrospectively evaluated the charts of all patients who underwent knee arthroscopy under general anesthesia (group GA) or spinal 2-chloroprocaine (group SA) between June 2012, when chloroprocaine was available for the first time, and December 2012. We collected the anesthesia time and the number of patients able to bypass the PACU. Moreover, we looked at hospital discharge time and we performed a pharmaco-economic analysis. RESULTS: 61 charts were evaluated, 5 patients were excluded for insufficient data. The anesthesia time was comparable between the two groups. All patients in group SA were able to bypass the PACU versus only 18% in group GA. We observed a clinically significant reduction in terms of discharge time (203 vs 326 minutes) and cost of materials and employers involved patients' care (53 vs 78 swiss franks) when spinal 1% 2-chloroprocaine was used. CONCLUSION: The right selection of the local anesthetic makes spinal anesthesia a suitable anesthetic technique for ultra-short outpatient procedures. If short acting local anesthetics are involved, spinal anesthesia could be competitive versus general anesthesia.

A prospective, double-blinded, randomized, clinical trial comparing the efficacy of 40 mg and 60 mg hyperbaric 2% prilocaine versus 60 mg plain 2% prilocaine for intrathecal anesthesia in ambulatory surgery.

BACKGROUND: In this prospective, double-blind, randomized trial we compared 60 mg and 40 mg of 2% hyperbaric prilocaine with 60 mg of 2% plain prilocaine for spinal anesthesia in terms of sensory block onset in outpatients undergoing elective short-duration (<60 minutes) surgery under spinal anesthesia. METHODS: Ninety patients were enrolled and randomly allocated to receive 1 of the 3 treatments. Times to sensory and motor block onsets, time to the maximum sensory block level, readiness for surgery, time to first urinary voiding, time to Bromage's score 0, and side effects were registered blindly. A blinded observer also questioned patients about transient neurological symptoms 24 hours and 7 days after spinal anesthesia. RESULTS: Mean times to achieve a T10 level of sensory block were comparable in the 3 groups. However, 20% of patients receiving plain prilocaine did not achieve a T10 level. The 2 hyperbaric dosages (60 mg and 40 mg) showed significantly faster times to motor block onset (P = 0.0091, P = 0.0097), to the maximum sensory block level (P = 0.0297, P = 0.0183), to motor block offset (P = 0.0004, P < 0.0001), and to first urinary voiding (P = 0.0013, P = 0.0002, respectively) than did plain prilocaine. No major adverse reactions or transient neurological symptoms were observed in the study. CONCLUSIONS: Spinal anesthesia with 60 mg or 40 mg of 2% hyperbaric prilocaine is comparable to 60 mg of 2% plain prilocaine in terms of onset of sensory block at T10. The hyperbaric solution showed faster times to motor block onset and shorter duration of surgical block, suggesting its superiority for the ambulatory setting.