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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

IL ‐2‐related regulatory CD4 T‐cell deficiency leads to the development of lung fibrosis and vascular remodeling

International audienceObjectives: Systemic sclerosis (SSc) is a dreadful autoimmune disease characterized by severe lung outcomes reducing life expectancy. Fra2TG mice offer the opportunity to decipher the relationships between the immune system and lung fibrosis. We herein investigated whether Fra2TG mice lung phenotype could result from an imbalance between the effector and the regulatory arms of the CD4 T-cell compartment.Methods: The homeostasis and phenotype of peripheral CD4 T cells from Fra2TG and control mice were first extensively characterized by multicolor flow cytometry. Then, different cures aimed at restoring regulatory CD4 T-cell (Treg) homeostasis have been tested, including adoptive transfer of Treg cells and treatment with low-dose IL-2.Results: Fra2TG mice exhibited a marked decrease in the proportion and absolute number of peripheral Treg cells which precedes the accumulation of activated, TH 2-polarized, CD4 T cells. This defect in Treg-cell homeostasis derived from combined mechanisms including an impaired generation of these cells in both the thymus and the periphery. The impaired ability of peripheral conventional CD4 T cells to produce IL-2 may greatly participate to Treg-cell deficiency in Fra2TG mice. Remarkably, adoptive transfer of Tregs, low-dose IL-2 therapy or combination of both all corrected the phenotype of Fra2TG mice, with a significant reduction in pulmonary parenchymal fibrosis and lung vascular remodeling.Conclusion: Immunotherapies aiming at restoring Treg-cell homeostasis could be relevant in SSc. An intervention based on low-dose IL-2 injections, as already proposed in other autoimmune diseases, could be the most suitable modality for future developments

Single-Molecule Study of Ribosome Hierarchic Dynamics at the Peptidyl Transferase Center

During protein biosynthesis the ribosome moves along mRNA in steps of precisely three nucleotides. The mechanism for this ribosome motion remains elusive. Using a classification algorithm to sort single-molecule fluorescence resonance energy transfer data into subpopulations, we found that the ribosome dynamics detected at the peptidyl transferase center are highly inhomogeneous. The pretranslocation complex has at least four subpopulations that sample two hybrid states, whereas the posttranslocation complex is mainly static. We observed transitions among the ribosome subpopulations under various conditions, including 1), in the presence of EF-G; 2), spontaneously; 3), in different buffers, and 4), bound to antibiotics. Therefore, these subpopulations represent biologically active ribosomes. One key observation indicates that the Hy2 hybrid state only exists in a fluctuating ribosome subpopulation, which prompts us to propose that ribosome dynamics are hierarchically arranged. This proposal may have important implications for the regulation of cellular translation rates