Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).

BACKGROUND: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. METHODS: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.

Healthcare resource utilisation and predictors for critical care unit admissions after primary bariatric surgery in an Australian public hospital setting: an exploratory study using a mixed-methods approach.

Objectives The aim of this exploratory study was to investigate resource use and predictors associated with critical care unit (CCU) admission after primary bariatric surgery within the Tasmanian public healthcare system. Methods Patients undergoing primary bariatric surgery in the Tasmanian Health Service (THS) public hospital system between 7 July 2013 and 30 June 2019 were eligible for inclusion in this study. The THS provides two levels of CCU support, an intensive care unit (ICU) and a high dependency unit (HDU). A mixed-methods approach was performed to examine the resource use and predictors associated with overall CCU admission, as well as levels of HDU and ICU admission. Results There were 254 patients in the study. Of these, 44 (17.3%) required 54 postoperative CCU admissions, with 43% requiring HDU support and 57% requiring more resource-demanding ICU support. Overall, CCU patients were more likely to have higher preoperative body mass index and multimorbidity and to undergo sleeve gastrectomy or gastric bypass. Patients undergoing gastric banding were more likely to require HDU rather than ICU support. Total hospital stays and median healthcare costs were higher for CCU (particularly ICU) patients than non-CCU patients. Conclusions Bariatric surgery patients often have significant comorbidities. This study demonstrates that patients with higher levels of morbidity are more likely to require critical care postoperatively. Because this is elective surgery, being able to identify patients who are at increased risk is important to plan either the availability of critical care or even interventions to improve patients' preoperative risk. Further work is required to refine the pre-existing conditions that contribute most to the requirement for critical care management (particularly in the ICU setting) in the perioperative period. What is known about the topic? Few studies (both Australian and international) have investigated the use of CCUs after bariatric surgery. Those that report CCU admission rates are disparate across the contemporaneous literature, reflecting the different healthcare systems and their associated incentives. In Australia, the incidence and utilisation of CCUs (consisting of HDUs and ICUs) after bariatric surgery have only been reported using Western Australian administrative data. What does the paper add? CCU patients were more likely to have a higher preoperative body mass index and multimorbidity and to undergo a sleeve gastrectomy or gastric bypass procedure. Just over half (57%) of these patients were managed in the ICU. Sleeve gastrectomy patients had a higher incidence of peri- and postoperative complications that resulted in an unplanned ICU admission. Hospital length of stay and aggregated costs were higher for CCU (particularly ICU) patients. What are the implications for practitioners? The association of increased CCU (particularly ICU) use with multimorbidity and peri- and postoperative complications could enable earlier recognition of patients that are more likely to require CCU and ICU support, therefore allowing improved planning when faced with increasing rates of bariatric surgery. We suggest streamlined clinical guidelines that anticipate CCU support for people with severe and morbid obesity who undergo bariatric surgery should be considered from a national perspective.