Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

Are validated outcome measures used in distal radial fractures truly valid?

Objectives Patient-reported outcome measures (PROMs) are often used to evaluate the outcome of treatment in patients with distal radial fractures. Which PROM to select is often based on assessment of measurement properties, such as validity and reliability. Measurement properties are assessed in clinimetric studies, and results are often reviewed without considering the methodological quality of these studies. Our aim was to systematically review the methodological quality of clinimetric studies that evaluated measurement properties of PROMs used in patients with distal radial fractures, and to make recommendations for the selection of PROMs based on the level of evidence of each individual measurement property. Methods A systematic literature search was performed in PubMed, EMbase, CINAHL and PsycINFO databases to identify relevant clinimetric studies. Two reviewers independently assessed the methodological quality of the studies on measurement properties, using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Level of evidence (strong / moderate / limited / lacking) for each measurement property per PROM was determined by combining the methodological quality and the results of the different clinimetric studies. Results In all, 19 out of 1508 identified unique studies were included, in which 12 PROMs were rated. The Patient-rated wrist evaluation (PRWE) and the Disabilities of Arm, Shoulder and Hand questionnaire (DASH) were evaluated on most measurement properties. The evidence for the PRWE is moderate that its reliability, validity (content and hypothesis testing), and responsiveness are good. The evidence is limited that its internal consistency and cross-cultural validity are good, and its measurement error is acceptable. There is no evidence for its structural and criterion validity. The evidence for the DASH is moderate that its responsiveness is good. The evidence is limited that its reliability and the validity on hypothesis testing are good. There is no evidence for the other measurement properties. Conclusion According to this systematic review, there is, at best, moderate evidence that the responsiveness of the PRWE and DASH are good, as are the reliability and validity of the PRWE. We recommend these PROMs in clinical studies in patients with distal radial fractures; however, more clinimetric studies of higher methodological quality are needed to adequately determine the other measurement propertie

Are the patient-rated wrist evaluation (PRWE) and the disabilities of the arm, shoulder and hand (DASH) questionnaire used in distal radial fractures truly valid and reliable?

Objectives The patient-rated wrist evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures (PROMs) used for clinical and research purposes. Methodological high-quality clinimetric studies that determine the measurement properties of these PROMs when used in patients with a distal radial fracture are lacking. This study aimed to validate the PRWE and DASH in Dutch patients with a displaced distal radial fracture (DRF). Methods The intraclass correlation coefficient (ICC) was used for test-retest reliability, between PROMs completed twice with a two-week interval at six to eight months after DRF. Internal consistency was determined using Cronbach's a for the dimensions found in the factor analysis. The measurement error was expressed by the smallest detectable change (SDC). A semi-structured interview was conducted between eight and 12 weeks after DRF to assess the content validity. Results A total of 119 patients (mean age 58 years (sd 15)), 74% female, completed PROMs at a mean time of six months (sd 1) post-fracture. One overall meaningful dimension was found for the PRWE and the DASH. Internal consistency was excellent for both PROMs (Cronbach's a 0.96 (PRWE) and 0.97 (DASH)). Test-retest reliability was good for the PRWE (ICC 0.87) and excellent for the DASH (ICC 0.91). The SDC was 20 for the PRWE and 14 for the DASH. No floor or ceiling effects were found. The content validity was good for both questionnaires. Conclusion The PRWE and DASH are valid and reliable PROMs in assessing function and disability in Dutch patients with a displaced DRF. However, due to the high SDC, the PRWE and DASH are less useful for individual patients with a distal radial fracture in clinical practic

Spectrum bias, a common unrecognised issue in orthopaedic agreement studies DO CT SCANS REALLY INFLUENCE THE AGREEMENT ON TREATMENT PLANS IN FRACTURES OF THE DISTAL RADIUS?

Objectives Current studies on the additional benefit of using computed tomography (CT) in order to evaluate the surgeons' agreement on treatment plans for fracture are inconsistent. This inconsistency can be explained by a methodological phenomenon called 'spectrum bias', defined as the bias inherent when investigators choose a population lacking therapeutic uncertainty for evaluation. The aim of the study is to determine the influence of spectrum bias on the intra-observer agreement of treatment plans for fractures of the distal radius. Methods Four surgeons evaluated 51 patients with displaced fractures of the distal radius at four time points: T1 and T2: conventional radiographs; T3 and T4: radiographs and additional CT scan (radiograph and CT). Choice of treatment plan (operative or non-operative) and therapeutic certainty (five-point scale: very uncertain to very certain) were rated. To determine the influence of spectrum bias, the intra-observer agreement was analysed, using Kappa statistics, for each degree of therapeutic certainty. Results In cases with high therapeutic certainty, intra-observer agreement based on radiograph was almost perfect (0.86 to 0.90), but decreased to moderate based on a radiograph and CT (0.47 to 0.60). In cases with high therapeutic uncertainty, intra-observer agreement was slight at best (-0.12 to 0.19), but increased to moderate based on the radiograph and CT (0.56 to 0.57). Conclusion Spectrum bias influenced the outcome of this agreement study on treatment plans. An additional CT scan improves the intra-observer agreement on treatment plans for a fracture of the distal radius only when there is therapeutic uncertainty. Reporting and analysing intra-observer agreement based on the surgeon's level of certainty is an appropriate method to minimise spectrum bia

Can experienced surgeons predict the additional value of a CT scan in patients with displaced intra-articular distal radius fractures?

Abstract There are no clear guidelines when an additional CT scan should be obtained for the treatment of displaced intra-articular distal radius fractures (DRF). This study aimed to investigate whether surgeons can predict the usefulness of CT scans to facilitate choice of treatment plan and/or pre-operative planning for DRF. Four surgeons evaluated 51 patients with displaced DRF. The choice of treatment (operative or nonoperative) was based on conventional radiographs. Subsequently, the surgeons were asked whether they would have requested an additional CT scan to determine this treatment choice, and also whether they required a CT scan for pre-operative planning. After 4 weeks, the additional CT scan was provided and the cases were assessed again. Based on these data, we calculated the number needed to scan (NNS) and number needed to harm (NNH) for two decision models. Model 1: Only provide a CT scan if the surgeon requested one based on their judgment of the X-rays. Model 2: CT scans for all displaced intra-articular DRF. For choice of treatment, the NNS was lower for model 1 than for model 2 (2.6 vs. 4.3) and the NNH is higher for model 1 (3.1 vs. 1.3). For pre-operative planning, the NNS (1.3 vs. 1.4) and NNH (3.7 vs. 3.4) were comparable for both models. Surgeons are able to predict the usefulness of an additional CT scan for intra-articular displaced DRF for OR indication. However, for pre-operative planning the usefulness of a CT scan is much harder to predict

A tailored intervention does not reduce low value MRI’s and arthroscopies in degenerative knee disease when the secular time trend is taken into account: a difference-in-difference analysis

Purpose: To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients ≥ 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group). Methods: All patients with degenerative knee disease ≥ 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI’s and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016–June 2017) and after introduction of the intervention (July 2017–December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital. Results: 136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (β = − 0.15, P < 0.001) and by 0.19% per month for arthroscopy (β = − 0.19, P < 0.001). However, these changes over time did not differ between intervention and control hospitals, neither for MRI (β = − 0.74, P = 0.228) nor arthroscopy (β = 0.13, P = 0.688). Conclusions: The extent to which patients ≥ 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands. Level of evidence: III

The value of nonoperative versus operative treatment of frail institutionalized elderly patients with a proximal femoral fracture in the shade of life (FRAIL-HIP); protocol for a multicenter observational cohort study

Background: Proximal femoral fractures are strongly associated with morbidity and mortality in elderly patients. Mortality is highest among frail institutionalized elderly with both physical and cognitive comorbidities who consequently have a limited life expectancy. Evidence based guidelines on whether or not to operate on these patients in the case of a proximal femoral fracture are lacking. Practice variation occurs, and it remains unknown if nonoperative treatment would result in at least the same quality of life as operative treatment. This study aims to determine the effect of nonoperative management versus operative management of proximal femoral fractures in a selected group of frail institutionalized elderly on the quality of life, level of pain, rate of complications, time to death, satisfaction of the patient (or proxy) and the caregiver with the management strategy, and health care consumption. Methods: This is a multicenter, observational cohort study. Frail institutionalized elderly (70 years or older with a body mass index < 18.5, a Functional Ambulation Category of 2 or lower pre-trauma, or an American Society of Anesthesiologists score of 4 or 5), who sustained a proximal femoral fracture are eligible to participate. Patients with a pathological or periprosthetic fractures and known metastatic oncological disease will be excluded. Treatment decision will be reached following a structured shared decision process. The primary outcome is quality of life (Euro-QoL; EQ-5D-5 L). Secondary outcome measures are quality of life measured with the QUALIDEM, pain level (PACSLAC), pain medication use, treatment satisfaction of patient (or proxy) and caregivers, quality of dying (QODD), time to death, and direct medical costs. A cost-utility and cost-effectiveness analysis will be done, using the EQ-5D utility score and QUALIDEM score, respectively. Non-inferiority of nonoperative treatment is assumed with a limit of 0.15 on the EQ-5D score. Data will be acquired at 7, 14, and 30 days and at 3 and 6 months after trauma. Discussion: The results of this study will provide insight into the true value of nonoperative treatment of proximal femoral fractures in frail elderly with a limited life expectancy. The results may be used for updating (inter)national treatment guidelines. Trial registration: The study is registered at the Netherlands Trial Register (NTR7245; date 10-06-2018)

Accelerated surgery versus standard care in hip fracture (HIP ATTACK) : an international, randomised, controlled trial

Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4\u20139) in the accelerated-surgery group and 24 h (10\u201342) in the standard-care group (p&lt;0\ub70001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0\ub791 (95% CI 0\ub772 to 1\ub714) and absolute risk reduction (ARR) of 1% ( 121 to 3; p=0\ub740). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0\ub797 (0\ub783 to 1\ub713) and an ARR of 1% ( 122 to 4; p=0\ub771). Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Funding: Canadian Institutes of Health Research