Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

ROS Accumulation and TTC Reduction in Growing Embryo of Crithmum maritimum L. Isolated from Water or Salt Imbibed Seeds

The salinity induced inhibition of seeds germination remains not clear at physiological levels. The aims of this study is to investigate the effect of salt on germination, embryo growth, superoxide anion radical (O2·-) and the respiratory activity (TTC reduction) in Crithmum maritimum L. seeds. Thus the embryo growth, in situ localization of respiratory activity and superoxide anion radical (O2·-) localization, were investigated. Chlorure 2, 3, 5-triphényltétrazolium (TTC) reduction test and superoxide anion radical (O2·-) localization with Nitroblue Tetrazolium Chloride (NBT) were performed in embryo isolated from seeds of the halophyte Crithmum maritimum L either sown in distilled water or in 200 mM NaCl. The key results show that germination was maximal (90 %) in distilled water, but was fully inhibited following seed exposure to NaCl. The completion of the embryo growth (ca. 2 mm length) leading to the radicle emergence took 6 d in H2O, but was markedly delayed by salt. NaCl reduced the elongation zone in the embryo axis, hence indicating that the cell division and/or cell elongation were disturbed by salinity. The respiratory activity (TTC reduction) and O2·- production in the cotyledon were significantly lowered by salinity

Relationship Between Ion Content in Seed and Spongy Coat of the Medicinal Halophyte Crithmum maritimum L. and Germination Capacity

Halophytes thrive in a wide range of habitats and climates, which may largely determine the seed mineral content, and hence influence both their germination capacity and their subsequent establishment. In order to assess this hypothesis, we performed a comparative study on three Tunisian proveniences of the perennial oilseed halophyte Crithmum maritimum L. The ion (Cl-, K+, and Na+) contents in seeds and fruits were determined and their likely relationship to germination capacity was addressed. Whether seeds were sown in distilled water or under moderate salt solution (100 mM NaCl) germination of the three proveniences was negatively correlated with the seed K+, Na+ and Cl- content. The spongy coats (fruits) were found to accumulate much more Na+ and Cl- than seeds (up to aprox. 8- and 11- fold, respectively for Na+ and Cl-), indicating that efficient mechanisms may take place in order to protect seeds from the harmful accumulation of salt. In addition, the higher selectivity for K+ vs. Na+ within seeds as compared to fruits seemed to be a determining factor in germination capacity of this species

Relationship Between Ion Content in Seed and Spongy Coat of the Medicinal Halophyte Crithmum maritimum L. and Germination Capacity

Halophytes thrive in a wide range of habitats and climates, which may largely determine the seed mineral content, and hence influence both their germination capacity and their subsequent establishment. In order to assess this hypothesis, we performed a comparative study on three Tunisian proveniences of the perennial oilseed halophyte Crithmum maritimum L. The ion (Cl-, K+, and Na+) contents in seeds and fruits were determined and their likely relationship to germination capacity was addressed. Whether seeds were sown in distilled water or under moderate salt solution (100 mM NaCl) germination of the three proveniences was negatively correlated with the seed K+, Na+ and Cl- content. The spongy coats (fruits) were found to accumulate much more Na+ and Cl- than seeds (up to aprox. 8- and 11- fold, respectively for Na+ and Cl-), indicating that efficient mechanisms may take place in order to protect seeds from the harmful accumulation of salt. In addition, the higher selectivity for K+ vs. Na+ within seeds as compared to fruits seemed to be a determining factor in germination capacity of this species

Differential Responses in Potassium Absorption and Use Efficiencies in the Halophytes Catapodium rigidum and Hordeum maritimum to Various Potassium Concentrations in the Medium

The changes in biomass production, root length, mineral nutrition, potassium absorption efficiency (KAE), and potassium use efficiency (KUE) of the halophytes Catapodium rigidum and Hordeum maritimum in response to potassium availability were assessed under natural conditions. Plants were cultivated in the greenhouse of the experimental station of the Biotechnology Centre of Borj Cédria (a Mediterranean coastal area) 30 km south-east of Tunis for four months from the autumn to winter of 2007–2008. H. maritimum biomass production was not significantly affected by the K+ concentration, but C. rigidum growth was increased significantly with increasing K+ concentration in the medium. Root/shoot dry weight ratio remained constant in C. rigidum, but decreased significantly at 1000 and 3000 µM K+ in H. maritimum. KAE increased but KUE decreased significantly with increasing K+ concentration in the medium in both species. However, KAE was higher in H. maritimum than in C. rigidum showing a contrasting response to K+ concentration between the two species. Overall, the maintenance of a cationic balance may be explained by cation antagonism. The lower K+ requirement of H. maritimum to express its optimal growth can be attributed to its higher efficiency to acquire and transfer K+ to shoots