Preoperative Psychopharmacological Treatment is Not a Risk factor for Poorer Patient-Reported Improvements 12 months After Hip or Knee Arthroplasty: A Multicenter Registry-Based Cohort study of 7,247 Procedures.

BACKGROUND: Preoperative psychopharmacological treatment (PPT) has been associated with increased hospital length of stay and readmission rate after hip and knee arthroplasty. However, little is known regarding the association between PPT and improvements in patient-reported outcomes postoperatively in a multicenter fast-track setting. Thus, the primary objective was to investigate whether PPT is a risk factor for poorer patient-reported improvements 12 months after surgery. Secondary objectives included assessment of additional time points and subgroups of PPT. METHODS: This multicenter registry-based cohort study included 4,021 primary hip and 3,226 primary knee arthroplasties performed from 2016 to 2020 at three fast-tack departments in Denmark due to primary osteoarthritis. The Oxford Hip/Knee Score (OHS/OKS), EQ-5D-3/5L, and EQ visual analog scale (VAS) were collected at baseline and three, six, 12, and 24 months after surgery. Exposure status was assigned using the Danish National Prescription Registry. Marginal mean differences (MD) with 95% confidence intervals (CI) were estimated using multilevel Tobit regression and adjusted for age, sex, and the Charlson Comorbidity Index obtained from the Danish National Patient Register. RESULTS: No associations were found between PPT and improvements in OHS (MD -0.5, CI -1.4 to 0.4) or OKS (MD -0.3, CI -1.2 to 0.5) after 12 months. However, PPT was associated with lower baseline OHS (MD -1.4, CI -2.2 to -0.6) and OKS (MD -2.1, CI -2.9 to -1.3), and 12 month follow-up OHS (MD -1.9, CI -2.8 to -1.1) and OKS (MD -2.4, CI -3.2 to -1.6). Similar findings were observed at other time points, using EQ-5D-3/5L or EQ VAS, and when evaluating PPT subgroups. CONCLUSION: In hip and knee arthroplasty, PPT was not a risk factor for poorer patient-reported improvements 12 months after surgery. However, PPT was associated with marginally poorer baseline and follow-up scores. Thus, arthroplasties remain effective treatments despite PPT from a patient-centered perspective.

Why do patients stay in hospital after enhanced recovery thoracoscopic wedge resection? A prospective observational study.

OBJECTIVES: This single-centre prospective observational study aimed to investigate reasons for prolonged hospitalization [over the median length of stay (LOS)] after enhanced recovery thoracoscopic [ERAS 3-port video-assisted thoracoscopic surgery (VATS)] wedge resection. METHODS: All patients were evaluated twice-daily by an investigator for reasons of hospitalization. Each reason was analysed individually. Predictors for prolonged hospitalization were identified using a multivariable backward stepwise logistic regression model. RESULTS: A total of 150 consecutive patients (lymphadenectomy 8.7%) were included from November 2022 to December 2023, with a median LOS of 1 (interquartile range 1-2) day. Of these, 55 patients (36.7%) experienced prolonged hospitalization. The main reasons included postoperative pain (16.0%), air leak (14.7%) and social factors (14.7%), followed by oxygen dependency (7.3%), gastrointestinal factors (5.3%), urinary factors (4.7%), pneumonia (1.3%), pleural effusion (1.3%), chylothorax (0.7%), atrial fibrillation (0.7%), confusion (0.7%) and fatigue (0.7%). Multivariable analysis revealed that an increase in the percentage of predicted forced expiratory volume in 1 s (FEV1%pre) by 1% [odds ratio (OR) 0.41, P = 0.023) and percentage of predicted diffusing capacity for carbon monoxide (DLCO%pre) by 1% (OR 0.95, P = 0.002) decreased likelihood of prolonged hospitalization. Conversely, each additional pack-year (OR 1.01, P = 0.028) and living alone (OR 3.55, P = 0.005) increased the risk of prolonged hospitalization. CONCLUSIONS: Prolonged hospitalization (LOS > 1 day) after ERAS 3-port VATS wedge resection, with 8.7% lymphadenectomy, was mainly due to pain, air leak and social factors. Smokers with decreased FEV1%pre or DLCO%pre and patient living alone were at increased risk. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT06118593 (https://clinicaltrials.gov/study/NCT06118593?cond=why%20in%20hospital&rank=2).

Perioperative association between c-reactive protein, pain catastrophizing and acute pain after total knee arthroplasty: A secondary analysis of two randomised trials.

BACKGROUND: Total knee arthroplasty is associated with an inflammatory response and high levels of pain in a subset of patients. Pain catastrophizing has been associated with acute postoperative pain. The association between these variables has not been investigated in an optimised fast-track setup including preoperative glucocorticoids. The aim of this study was, first, to investigate the correlation between the increase in postoperative c-reactive protein (CRP) and acute postoperative pain after total knee arthroplasty, and second, to investigate the correlation between the increase in CRP and preoperative pain catastrophizing. METHODS: This study is a secondary analysis of data from 119 patients participating in two randomised controlled trials. Correlation analyses were performed for preoperative CRP and CRP increase at 24 and 48 h and pain during a well-defined mobilisation at 24 and 48 h after total knee arthroplasty. Additionally, correlation analyses were performed between CRP increase and pain catastrophizing using the pain catastrophizing scale. RESULTS: There was no correlation between preoperative CRP or postoperative CRP increase and pain at both 24 and 48 h. Analyses were similar when separated into high and low pain catastrophizers. There was no correlation between preoperative CRP or postoperative CRP increase and pain catastrophizing. CONCLUSION: There was no association between the postoperative CRP response and postoperative acute pain or pain catastrophizing in patients undergoing total knee arthroplasty in a well-defined multimodal fast-track regime including preoperative glucocorticoids. These results suggest that acute pain after knee arthroplasty is not reflected by CRP when applying preoperative glucocorticoids.

Predictors of subacute postoperative pain after total knee arthroplasty: A secondary analysis of two randomized trials.

BACKGROUND: Methods for identifying high-pain responders undergoing total knee arthroplasty remain important to improve individualized pain management. This study aimed at evaluating pre- and perioperative predictors of pain on Days 2-7 after total knee arthroplasty. METHODS: This is a secondary analysis of data from 227 patients participating in two randomized trials. Pain outcomes were mean pain during walking on Days 2-7 and on Days 2, 4 and 7. Multivariable linear and logistic regressions were carried out in two steps. First, only preoperative available variables including demographics, comorbidities, pain catastrophizing scale and preoperative pain were evaluated while controlling for trial intervention and recruitment site. In the second step, perioperative variables and pain during walking 24 h postoperatively were added. RESULTS: The model with only preoperative predictors for mean pain Days 2-7 showed preoperative pain (R-squared 0.097) as the only predictor. In the second model, adding postoperative available variables, only pain 24 h postoperatively (R-squared 0.248) was significant, with a significant main effect of recruitment site. Results for the separate day analysis similarly showed preoperative pain and pain during walking 24 h postoperatively as predictors. The overall best sensitivity (60%) and specificity (74%) for predicting a high-subacute postoperative pain response on Days 2-7 was with cut-off values of VAS 45.5 (out of 100) for pain during walking 24 h postoperatively. CONCLUSIONS: Postoperative pain during walking at 24 h is predictive of subacute postoperative pain on Days 2-7 after total knee arthroplasty, while preoperative pain was only a weak predictor. SIGNIFICANCE STATEMENT: This study investigated factors associated with pain after total knee arthroplasty beyond the immediate postoperative period. The analysis revealed significant associations between preoperative pain levels and, particularly, pain 24 h postoperatively, with subsequent subacute pain the following week. These findings can assist in identifying patients who would benefit from enhanced, individualized analgesic interventions to facilitate postoperative recovery.

Challenges in Enhanced Recovery After Surgery (ERAS) research.

Despite the general agreement that implementation of Enhanced Recovery After Surgery (ERAS) pathways decrease hospital length of stay, a continuous challenge that has often been neglected is a procedure- and patient-specific approach. For example, asking 'Why is the patient still in hospital?' is the original premise for ERAS. Outcomes improve with increased compliance with recommended elements, but overcomplication of pathways can lead to cherry picking of elements that are convenient, resulting in 'partial ERAS'. As there are few high-quality randomised clinical trials (RCTs) that evaluate the specific role of individual preoperative, intraoperative, and postoperative elements, challenges lie ahead to identify essential ERAS elements to facilitate more widespread implementation. To achieve this goal, the balance between large RCTs and smaller detailed hypothesis-generating observational studies needs to be addressed in order to enhance knowledge and limit waste of research resources.

Preoperative high dose of dexamethasone in emergency laparotomy: randomized clinical trial.

BACKGROUND: Patients undergoing emergency laparotomy present with a profound inflammatory response, which could be an independent pathophysiological component in prolonged recovery. The aim of this study was to investigate the effects of a single preoperative high dose of intravenous dexamethasone on the inflammatory response and recovery after emergency laparotomy. METHODS: In this double-blinded placebo-controlled trial, patients were prospectively stratified according to surgical pathology (intestinal obstruction and perforated viscus) and randomized to preoperative 1 mg/kg dexamethasone or placebo at a ratio of 1 : 1. The primary outcome was C-reactive protein on postoperative day 1. Secondary outcomes were postoperative recovery, morbidity, and mortality. RESULTS: A total of 120 patients were included in the trial. On postoperative day 1, the C-reactive protein response was significantly lower in the dexamethasone group (a median of 170 versus 220 mg/l for dexamethasone and for placebo respectively; P = 0.015; mean difference = 49 (95% c.i. 13 to 85) mg/l) and when stratified according to intestinal obstruction (a median of 60 versus 160 mg/l for dexamethasone and for placebo respectively; P = 0.002) and perforated viscus (a median of 230 versus 285 mg/l for dexamethasone and for placebo respectively; P = 0.035). Dexamethasone administration was associated with improved recovery (better haemodynamics, better pulmonary function, less fatigue, and earlier mobilization). Furthermore, the dexamethasone group had a lower 90-day mortality rate (7% versus 23% for dexamethasone and for placebo respectively; relative risk 0.33 (95% c.i. 0.11 to 0.93); P = 0.023) and a decreased incidence of postoperative major complications (27% versus 45% for dexamethasone and for placebo respectively; relative risk 0.62 (95% c.i. 0.37 to 1.00); P = 0.032). CONCLUSION: A single preoperative high dose of intravenous dexamethasone significantly reduces the inflammatory response after emergency laparotomy and is associated with enhanced recovery and improved outcome. REGISTRATION NUMBER: NCT04791566 (http://www.clinicaltrials.gov).

Outcome improvement for anaemia and iron deficiency in ERAS hip and knee arthroplasty: a descriptive analysis.

BACKGROUND AND PURPOSE: Preoperative anaemia including iron deficiency anaemia (IDA) is a well-established perioperative risk factor. However, most studies on iron therapy to treat IDA have been negative and few have been conducted within an enhanced recovery after surgery (ERAS) protocol. Furthermore, patients with IDA often have comorbidities not necessarily influenced by iron, but potentially influencing traditional study endpoints such as length of stay (LOS), morbidity, etc. The aim of this paper is to discuss patient-related challenges when planning outcome studies on the potential benefits of iron therapy in patients with IDA, based upon a large detailed prospective database in ERAS total hip (THA) and knee arthroplasty (TKA). METHODS: A prospective observational cohort study in ERAS THA and TKA from 2022 to 2023. Detailed complete follow-up through questionnaires and electronic medical records. RESULTS: Of 3655 included patients, 276 (7.6%) had IDA defined as a haemoglobin (Hb) of < 13.0 g/dL and transferrin saturation of 0.20, while 3379 had a Hb of ≥ 13.0. Patients with IDA were a median 5 years older than non-anaemics, with an increased fraction living alone (38.4% vs. 28.8%), using walking aids (54.3% vs 26.4%) and receiving home care (16.2% vs 4.7%). Fewer IDA patients were working (12.7% vs. 29.6%) and a median number of prescribed drugs was higher (10 vs. 6). Median LOS was 1 day in both IDA and non-anaemic patients, but a LOS of > 2 days occurred in 11.6% of patients with IDA vs. 4.3% in non-anaemics. The proportion with 30- or 90-day readmissions was 6.5% vs. 4.1% and. 13.4% vs6.0%, in patients with IDA and non-anaemics, respectively. However, potentially anaemia or iron deficiency-related causes of LOS > 2 days or 90-day readmissions were only 5.4% and 2.2% in patients with IDA and 1.9% and 1.0% in non-anaemics. CONCLUSION: Conventional randomised trials with single or composite "hard" endpoints are at risk of being inconclusive or underpowered due to a considerable burden of other patient-related risk factors and with postoperative complications which may not be modifiable by correction of IDA per se. We will propose to gain further insights from detailed observational and mechanistic studies prior to initiating extensive randomised studies.

Acute postoperative pain and catastrophizing in unicompartmental knee arthroplasty: a prospective, observational, single-center, cohort study.

BACKGROUND AND OBJECTIVES: Pain catastrophizing is associated with acute pain after total knee arthroplasty. However, the association between pain catastrophizing and acute pain after unicompartmental knee arthroplasty (UKA) remains unclear. METHODS: We investigated the incidence of predicted high-pain and low-pain responders, based on a preoperative Pain Catastrophizing Scale score >20 or ≤20, respectively, and the acute postoperative pain course in both groups. Patients undergoing UKA were consecutively included in this prospective observational cohort study. Pain at rest and during walking (5 m walk test) was evaluated preoperatively, at 24 hours postoperatively, and on days 2-7 using a pain diary. RESULTS: 125 patients were included, with 101 completing the pain diary. The incidence of predicted high-pain responders was 31% (95% CI 23% to 40%). The incidence of moderate to severe pain during walking at 24 hours postoperatively was 69% (95% CI 52% to 83%) in predicted high-pain responders and 66% (95% CI 55% to 76%) in predicted low-pain responders; OR 1.3 (95% CI 0.5 to 3.1). The incidence of moderate to severe pain at rest 24 hours postoperatively was 49% (95% CI 32% to 65%) in predicted high-pain responders and 28% (95% CI 19% to 39%) in predicted low-pain responders; OR 2.6 (95% CI 1.1 to 6.1; p=0.03). Pain catastrophizing was not associated with increased cumulated pain during walking on days 2-7. CONCLUSIONS: The incidence of predicted high-pain responders in UKA was slightly lower than reported in total knee arthroplasty. Additionally, preoperative pain catastrophizing was not associated with acute postoperative pain during walking.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Postoperative outcomes in patients with diabetes after enhanced recovery thoracoscopic lobectomy.

BACKGROUND: Diabetes is considered a general surgical risk factor, but with few data from enhanced recovery (ERAS) otherwise known to improve outcome. Therefore, this study aimed to investigate postoperative outcomes of patients with diabetes who underwent video-assisted thoracoscopic surgery (VATS) lobectomy in an established ERAS setting. METHODS: We retrospectively analysed outcome data (hospital stay (LOS), readmissions, and mortality) from a prospective database with consecutive unselected ERAS VATS lobectomies from 2012 to 2022. Complete follow-up was secured by the registration system in East Denmark. RESULTS: We included 3164 patients of which 323 had diabetes, including 186 treated with insulin and antidiabetic medicine, 35 with insulin only and 102 with antidiabetic medicine only. The median LOS was 3 days, stable over the study period. There were no differences in terms of LOS, postoperative complications, readmissions or 30 days alive and out of hospital. Patients with diabetes had significantly higher 30- and 90-day mortality rates compared to those without diabetes (p < .001), but also had higher preoperative comorbidity. Preoperative HbA1c levels did not correlate with postoperative outcomes. CONCLUSION: In an ERAS setting, diabetes may not increase the risk for prolonged LOS, complications, and readmissions after VATS lobectomy, however with higher 30- and 90-day mortality probably related to more preoperative comorbidities.

Psychopharmacological treatment in patients planned for hip or knee replacement.

Psychopharmacological treatment may be an independent risk factor for increased length of stay and readmission after hip and knee replacement. Thus, temporary perioperative discontinuation may be beneficial. However, little is known regarding the treatments, and not all are feasible to discontinue. Therefore, the aim of this study was to describe the treatments in terms of type, dose, duration, indication and initiating physician to assess the feasibility of temporary perioperative discontinuation. We included 482 patients planned for hip or knee replacement in psychopharmacological treatment for psychiatric disorders from 2021 to 2023 at five orthopaedic departments in Denmark. Most patients were treated with antidepressants (89%); most frequently, either selective serotonin reuptake inhibitors (SSRIs; 48%) or serotonin-norepinephrine reuptake inhibitors (SNRIs; 21%). The majority received monotherapy (70%); most frequently, an SSRI (36%) or an SNRI (12%). Most antidepressants were initiated by general practitioners (71%), and the treatments had lasted for more than a year (87%). The doses of SSRIs/SNRIs were moderate, and the most frequent indication for antidepressants was depression (77%). These results imply that temporary perioperative SSRI/SNRI discontinuation may be feasible in hip and knee replacement patients and support a future randomized controlled trial investigating the potential benefits of temporary discontinuation.

Implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting.

BACKGROUND AND PURPOSE: Length of hospital stay after hip and knee arthroplasty is about 1 day in Denmark with few patients discharged on the day of surgery. Hence, a protocol for multicenter implementation of discharge on day of surgery has been instituted. We aimed to describe the implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting. METHODS: We performed a prospective multicenter study from 7 public hospitals across Denmark. Patients were screened using well-defined in- and exclusion criteria and were discharged on day of surgery when fulfilling functional discharge criteria. The study period was from September 2022 to February 2023 with variable start of implementation. Data from the same centers in a 6-month period before the COVID pandemic from July 2019 to December 2019 was used for baseline control. RESULTS: Of 2,756 primary hip and knee arthroplasties, 37% (95% confidence interval [CI] 35-39) were eligible (range 21-50% in centers) and 52% (range 24-62%) of these were discharged on day of surgery. 21% (CI 20-23) of all patients (eligible and non-eligible) were discharged on day of surgery with a range of 10-31% within centers. This was an additional 15% (CI 13-17, P < 0.001) compared with patients discharged in the control period (6% in 2019). CONCLUSION: We found it possible to perform outpatient hip and knee replacement in 21% of patients in a public healthcare setting, probably to be increased with further center experience.

Protocol for a prospective multicentre cohort study to address the question whether diabetes and its management is still a risk factor in fast-track joint arthroplasty.

INTRODUCTION: Perioperative glycaemic control is important. However, the complexity of guidelines for perioperative diabetes management is complicated due to different and novel antihyperglycaemic medications, limited procedure-specific data and lack of data from implemented fast-track regimens which otherwise are known to reduce morbidity and glucose homeostasis disturbances. Consequently, outcome in patients with diabetes mellitus (DM) after surgery and the influence of perioperative diabetes management on postoperative recovery remains poorly understood. METHODS AND ANALYSIS: A prospective observational multicentre study involving 8 arthroplasty centres across Denmark with a documented implemented fast-track programme (median length of hospitalisation (LOS) 1 day). We will collect detailed perioperative data including preoperative haemoglobin A1c and antidiabetic treatment in 1400 unselected consecutive patients with DM undergoing hip and knee arthroplasty from September 2022 to December 2025, enrolled after consent. Follow-up duration is 90 days after surgery. The primary outcome is the proportion of patients with DM with LOS >4 days and 90-day readmission rate after fast-track total hip arthroplasty (THA), total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). The secondary outcome is the association between perioperative diabetes treatment and LOS >2 days, 90-day readmission rate, other patient demographics and Comprehensive Complication Index for patients with DM after THA/TKA/UKA in a fast-track regimen. ETHICS AND DISSEMINATION: The study will follow the principles of the Declaration of Helsinki and ICH-Good Clinical Practice guideline. Ethical approval was not necessary as this is a non-interventional observational study on current practice. The trial is registered in the Region of Southern Denmark and on ClinicalTrials.gov. The main results and all substudies of this trial will be published in peer-reviewed international medical journals. TRIAL REGISTRATION NUMBER: NCT05613439.

Postoperative orthostatic intolerance following fast-track unicompartmental knee arthroplasty: incidence and hemodynamics-a prospective observational cohort study.

BACKGROUND: Early postoperative mobilization is essential for early functional recovery but can be inhibited by postoperative orthostatic intolerance (OI). Postoperative OI is common after major surgery, such as total knee arthroplasty (TKA). However, limited data are available after less extensive surgery, such as unicompartmental knee arthroplasty (UKA). We, therefore, investigated the incidence of OI as well as cardiovascular and tissue oxygenation responses during early mobilization after UKA. METHODS: This prospective single-centre observational study included 32 patients undergoing primary UKA. Incidence of OI and cardiovascular and tissue oxygenation responses during mobilization were evaluated preoperatively, at 6 and 24 h after surgery. Perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain during mobilization and opioid usage were recorded. RESULTS: During mobilization at 6 h after surgery, 4 (14%, 95%CI 4-33%) patients experienced OI; however, no patients terminated the mobilization procedure prematurely. Dizziness and feeling of heat were the most common symptoms. OI was associated with attenuated systolic and mean arterial blood pressure responses in the sitting position (all p < 0.05). At 24 h after surgery, 24 (75%) patients had already been discharged, including three of the four patients with early OI. Only five patients were available for measurements, two of whom experienced OI; one terminated the mobilization procedure due to intolerable symptoms. We observed no statistically significant differences in perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain, or opioid usage between orthostatic intolerant and tolerant patients. CONCLUSIONS: The incidence of orthostatic intolerance after fast-track unicompartmental knee arthroplasty is low (~ 15%) and is associated with decreased orthostatic pressure responses. Compared to the previously described orthostatic intolerance incidence of ~ 40% following total knee arthroplasty, early orthostatic intolerance is uncommon after unicompartmental knee arthroplasty, suggesting a procedure-specific component. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov; registration number: NCT04195360, registration date: 13.12.2019.

Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

OBJECTIVE: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. METHODS: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. RESULTS: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. CONCLUSION: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Exploring the need for reconsideration of trial design in perioperative outcomes research: a narrative review.

"Enhanced recovery after surgery" is a multimodal effort to control perioperative pathophysiology and improve outcome. However, despite advances in perioperative care, postoperative complications and the need for hospitalisation and prolonged recovery continue to be challenging. This is further complicated by procedure-specific and patient-associated risk factors, given the increase in the number of elderly and frail patients with multiple comorbidities undergoing surgery. This paper is a critical assessment of current methodology for trials in perioperative medicine. We make a plea to reconsider the design of future interventional trials to improve surgical outcome, based upon studies of potentially effective interventions, but often without improvements in recovery. The complexity of perioperative pathophysiology necessitates a procedure- and patient-specific approach whenever outcome is assessed or interventions are planned. With improved understanding of perioperative pathophysiology, the way to improve outcomes looks promising, provided that knowledge and established enhanced recovery programmes are integrated in trial design. Funding: None.