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

Sox9 is critical for suppression of neurogenesis but not initiation of gliogenesis in the cerebellum

BACKGROUND: The high mobility group (HMG) family transcription factor Sox9 is critical for induction and maintenance of neural stem cell pool in the central nervous system (CNS). In the spinal cord and retina, Sox9 is also the master regulator that defines glial fate choice by mediating the neurogenic-to-gliogenic fate switch. On the other hand, the genetic repertoire governing the maintenance and fate decision of neural progenitor pool in the cerebellum has remained elusive. RESULTS: By employing the Cre/loxP strategy, we specifically inactivated Sox9 in the mouse cerebellum. Unexpectedly, the self-renewal capacity and multipotency of neural progenitors at the cerebellar ventricular zone (VZ) were not perturbed upon Sox9 ablation. Instead, the mutants exhibited an increased number of VZ-derived neurons including Purkinje cells and GABAergic interneurons. Simultaneously, we observed continuous neurogenesis from Sox9-null VZ at late gestation, when normally neurogenesis ceases to occur and gives way for gliogenesis. Surprisingly, glial cell specification was not affected upon Sox9 ablation. CONCLUSION: Our findings suggest Sox9 may mediate the neurogenic-to-gliogenic fate switch in mouse cerebellum by modulating the termination of neurogenesis, and therefore indicate a functional discrepancy of Sox9 between the development of cerebellum and other major neural tissues