Implications of Mean Pulmonary Arterial Wedge Pressure Trajectories in Pulmonary Arterial Hypertension.

Rationale: The mean pulmonary arterial wedge pressure (mPAWP) is the critical hemodynamic factor differentiating group 1 pulmonary arterial hypertension (PAH) from group 2 pulmonary hypertension associated with left heart disease. Despite the discrepancy between the mPAWP upper physiologic normal and current PAH definitions, the implications of the initial mPAWP for PAH clinical trajectory are poorly understood. Objectives: To model longitudinal mPAWP trajectories in PAH over 10 years and examine the clinical and hemodynamic factors associated with trajectory membership. Methods: Adult patients with PAH with two or more right heart catheterizations were identified from a multiinstitution healthcare system in eastern Massachusetts. mPAWP trajectories were constructed via group-based trajectory modeling. Feature selection was performed in least absolute shrinkage and selection operator regression. Logistic regression was used to assess associations between trajectory membership, baseline characteristics, and transplant-free survival. Measurements and Main Results: Among 301 patients with PAH, there were two distinct mPAWP trajectories, termed "mPAWP-high" (n = 71; 23.6%) and "mPAWP-low" (n = 230; 76.4%), based on the ultimate mPAWP value. Initial mPAWP clustered around median 12 mm Hg (interquartile range [IQR], 8-14 mm Hg) in the mPAWP-high and 9 mm Hg (IQR, 6-11 mm Hg) in the mPAWP-low trajectories (P < 0.001). After feature selection, initial mPAWP ⩾12 mm Hg predicted an mPAWP-high trajectory (odds ratio, 3.2; 95% confidence interval, 1.4-6.1; P = 0.0006). An mPAWP-high trajectory was associated with shorter transplant-free survival (vs. mPAWP-low, median, 7.8 vs. 11.3 yr; log-rank P = 0.017; age-adjusted P = 0.217). Conclusions: Over 10 years, the mPAWP followed two distinct trajectories, with 25% evolving into group 2 pulmonary hypertension physiology. Using routine baseline data, longitudinal mPAWP trajectory could be predicted accurately, with initial mPAWP ⩾12 mm Hg as one of the strongest predictors.

Opportunistic Treatment of Hepatitis C Infection Among Hospitalized People Who Inject Drugs (OPPORTUNI-C): A Stepped Wedge Cluster Randomized Trial.

BACKGROUND: We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID). METHODS: We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment. RESULTS: A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2-77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1-45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0-46.2]; risk ratio 1.9 [95% CI: 1.4-2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8-12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5-6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8-70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6-73.9]) during control conditions. CONCLUSIONS: An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation. Clinical Trials Registration. NCT04220645.

Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Investigating the missing-wedge problem in small-angle X-ray scattering tensor tomography across real and reciprocal space.

Small-angle-scattering tensor tomography is a technique for studying anisotropic nanostructures of millimetre-sized samples in a volume-resolved manner. It requires the acquisition of data through repeated tomographic rotations about an axis which is subjected to a series of tilts. The tilt that can be achieved with a typical setup is geometrically constrained, which leads to limits in the set of directions from which the different parts of the reciprocal space map can be probed. Here, we characterize the impact of this limitation on reconstructions in terms of the missing wedge problem of tomography, by treating the problem of tensor tomography as the reconstruction of a three-dimensional field of functions on the unit sphere, represented by a grid of Gaussian radial basis functions. We then devise an acquisition scheme to obtain complete data by remounting the sample, which we apply to a sample of human trabecular bone. Performing tensor tomographic reconstructions of limited data sets as well as the complete data set, we further investigate and validate the missing wedge problem by investigating reconstruction errors due to data incompleteness across both real and reciprocal space. Finally, we carry out an analysis of orientations and derived scalar quantities, to quantify the impact of this missing wedge problem on a typical tensor tomographic analysis. We conclude that the effects of data incompleteness are consistent with the predicted impact of the missing wedge problem, and that the impact on tensor tomographic analysis is appreciable but limited, especially if precautions are taken. In particular, there is only limited impact on the means and relative anisotropies of the reconstructed reciprocal space maps.

Pulmonary Artery Diastolic Pressure as a Surrogate for Pulmonary Capillary Wedge Pressure in Cardiogenic Shock.

BACKGROUND: It is common for clinicians to use the pulmonary artery diastolic pressure (PADP) as a surrogate for the pulmonary capillary wedge pressure (PCWP). Here, we determine the validity of this relationship in patients with various phenotypes of cardiogenic shock (CS). METHODS AND RESULTS: In this analysis of the Critical Care Cardiology Trials Network registry, we identified 1225 people admitted with CS who received pulmonary artery catheters. Linear regression, Bland-Altman and receiver operator characteristic analyses were performed to determine the strength of the association between PADP and PCWP in patients with left-, right-, biventricular, and other non-myocardia phenotypes of CS (eg, arrhythmia, valvular stenosis, tamponade). There was a moderately strong correlation between PADP and PCWP in the total population (r = 0.64, n = 1225) and in each CS phenotype, except for right ventricular CS, for which the correlation was weak (r = 0.43, n = 71). Additionally, we found that a PADP ≥ 24 mmHg can be used to infer a PCWP ≥ 18 mmHg with ≥ 90% confidence in all but the right ventricular CS phenotype. CONCLUSIONS: This analysis validates the practice of using PADP as a surrogate for PCWP in most patients with CS; however, it should generally be avoided in cases of right ventricular-predominant CS.

Prognostic Factors among Patients with Resected Non-Adenocarcinoma of the Lung.

INTRODUCTION: Few studies have investigated the prognostic factors for non-adenocarcinoma of the lung. We retrospectively evaluated the prognostic factors on the basis of histological type of non-adenocarcinoma of the lung treated by pulmonary resection. METHODS: We enrolled 266 patients with non-adenocarcinoma of the lung in this retrospective study: 196 with squamous cell carcinoma (SCC) and 70 with non-SCC. RESULTS: Relapse-free survival (RFS) did not differ significantly between SCC and non-SCC patients (p = 0.33). For SCC patients, RFS differed significantly between patients who underwent wedge resection and non-wedge resection (p < 0.01) and between patients with Clavien-Dindo grade ≥3a and 0-2 postoperative complications (p < 0.01). For non-SCC patients, RFS rates were significantly different in the groups divided at neutrophil-to-lymphocyte ratio = 2.40 (p = 0.02), maximum standardized uptake value (SUVmax) = 8.39 (p < 0.01), between patients with pathological stage (pStage) 0-I and with pStage more than II (p < 0.01). For SCC patients, male sex (p = 0.04), wedge resection (p = 0.01), and Clavien-Dindo grade ≥3a (p = 0.02) were significant factors for RFS in multivariate analysis. For non-SCC patients, neutrophil-to-lymphocyte ratio >2.40 (p < 0.01), SUVmax >8.39 (p = 0.01), and pStage ≥II (p = 0.03) were significant factors for RFS in multivariate analysis. CONCLUSION: RFS did not differ significantly differently between SCC and non-SCC patients. It is necessary to perform more than segmentectomy and to avoid severe postoperative complications for SCC patients. SUVmax might be an adaptation criterion of adjuvant chemotherapy for patients with non-adenocarcinoma and non-SCC of the lung.

Predictors of elaborated perineal or a combined abdominoperineal approach during repair for pelvic fracture urethral injury.

PURPOSE: A step-based anastomotic urethroplasty is a standard technique for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). We aim to identify pre-operative factors, including results of conventional radiological imaging, for prediction of elaborated perineal or a combined abdominoperineal procedure. METHODS: Retrospective observational study on 114 consecutive patients undergoing urethroplasty for PFUI between January 2020 and December 2022 was conducted. Surgical procedures were categorized according to the Webster classification into two groups: steps 1-2 (group 1) and steps 3-4 or a combined abdominoperineal repair (group 2). Pre-operative pattern results of RGU/VCUG were categorized regarding the relation between the proximal urethral stump with the pubic symphysis: posterior urethral stump below (pattern 1) or above (pattern 2) the lower margin of the pubic symphysis. Patient demographics were assessed. Univariate and multivariate logistic regression analyses were utilized. RESULTS: Overall, 102 patients were enrolled in the study for data analysis. On the multivariate logistic regression analysis, the presence of erectile dysfunction (OR 4.5; p = 0.014), prior combined treatment (endoscopic and urethroplasty) (OR 6.4; p = 0.018) and RGU/VCUG pattern 2 (OR 66; p < 0.001) significantly increased the likelihood of the need of step 3 or higher. CONCLUSIONS: The need of step 3 or higher during urethroplasty for PFUI can be predicted pre-operatively with conventional imaging (RGU/VCUG). Patients with proximal urethral stump above the lower margin of pubic symphysis were about 66 times more likely to need step 3 or higher during urethroplasty.

Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

Cluster randomized trial designs for modeling time-varying intervention effects.

Stepped-wedge cluster randomized trials (SW-CRTs) are typically analyzed assuming a constant intervention effect. In practice, the intervention effect may vary as a function of exposure time, leading to biased results. The estimation of time-on-intervention (TOI) effects specifies separate discrete intervention effects for each elapsed period of exposure time since the intervention was first introduced. It has been demonstrated to produce results with minimum bias and nominal coverage probabilities in the analysis of SW-CRTs. Due to the design's staggered crossover, TOI effect variances are heteroskedastic in a SW-CRT. Accordingly, we hypothesize that alternative CRT designs will be more efficient at modeling certain TOI effects. We derive and compare the variance estimators of TOI effects between a SW-CRT, parallel CRT (P-CRT), parallel CRT with baseline (PB-CRT), and novel parallel CRT with baseline and an all-exposed period (PBAE-CRT). We also prove that the time-averaged TOI effect variance and point estimators are identical to that of the constant intervention effect in both P-CRTs and PB-CRTs. We then use data collected from a hospital disinvestment study to simulate and compare the differences in TOI effect estimates between the different CRT designs. Our results reveal that the SW-CRT has the most efficient estimator for the early TOI effect, whereas the PB-CRT typically has the most efficient estimator for the long-term and time-averaged TOI effects. Overall, the PB-CRT with TOI effects can be a more appropriate choice of CRT design for modeling intervention effects that vary by exposure time.

Robust analysis of stepped wedge trials using composite likelihood models.

Stepped wedge trials (SWTs) are a type of cluster randomized trial that involve repeated measures on clusters and design-induced confounding between time and treatment. Although mixed models are commonly used to analyze SWTs, they are susceptible to misspecification particularly for cluster-longitudinal designs such as SWTs. Mixed model estimation leverages both "horizontal" or within-cluster information and "vertical" or between-cluster information. To use horizontal information in a mixed model, both the mean model and correlation structure must be correctly specified or accounted for, since time is confounded with treatment and measurements are likely correlated within clusters. Alternative non-parametric methods have been proposed that use only vertical information; these are more robust because between-cluster comparisons in a SWT preserve randomization, but these non-parametric methods are not very efficient. We propose a composite likelihood method that focuses on vertical information, but has the flexibility to recover efficiency by using additional horizontal information. We compare the properties and performance of various methods, using simulations based on COVID-19 data and a demonstration of application to the LIRE trial. We found that a vertical composite likelihood model that leverages baseline data is more robust than traditional methods, and more efficient than methods that use only vertical information. We hope that these results demonstrate the potential value of model-based vertical methods for SWTs with a large number of clusters, and that these new tools are useful to researchers who are concerned about misspecification of traditional models.

Power calculation for detecting interaction effect in cross-sectional stepped-wedge cluster randomized trials: an important tool for disparity research.

BACKGROUND: The stepped-wedge cluster randomized trial (SW-CRT) design has become popular in healthcare research. It is an appealing alternative to traditional cluster randomized trials (CRTs) since the burden of logistical issues and ethical problems can be reduced. Several approaches for sample size determination for the overall treatment effect in the SW-CRT have been proposed. However, in certain situations we are interested in examining the heterogeneity in treatment effect (HTE) between groups instead. This is equivalent to testing the interaction effect. An important example includes the aim to reduce racial disparities through healthcare delivery interventions, where the focus is the interaction between the intervention and race. Sample size determination and power calculation for detecting an interaction effect between the intervention status variable and a key covariate in the SW-CRT study has not been proposed yet for binary outcomes. METHODS: We utilize the generalized estimating equation (GEE) method for detecting the heterogeneity in treatment effect (HTE). The variance of the estimated interaction effect is approximated based on the GEE method for the marginal models. The power is calculated based on the two-sided Wald test. The Kauermann and Carroll (KC) and the Mancl and DeRouen (MD) methods along with GEE (GEE-KC and GEE-MD) are considered as bias-correction methods. RESULTS: Among three approaches, GEE has the largest simulated power and GEE-MD has the smallest simulated power. Given cluster size of 120, GEE has over 80% statistical power. When we have a balanced binary covariate (50%), simulated power increases compared to an unbalanced binary covariate (30%). With intermediate effect size of HTE, only cluster sizes of 100 and 120 have more than 80% power using GEE for both correlation structures. With large effect size of HTE, when cluster size is at least 60, all three approaches have more than 80% power. When we compare an increase in cluster size and increase in the number of clusters based on simulated power, the latter has a slight gain in power. When the cluster size changes from 20 to 40 with 20 clusters, power increases from 53.1% to 82.1% for GEE; 50.6% to 79.7% for GEE-KC; and 48.1% to 77.1% for GEE-MD. When the number of clusters changes from 20 to 40 with cluster size of 20, power increases from 53.1% to 82.1% for GEE; 50.6% to 81% for GEE-KC; and 48.1% to 79.8% for GEE-MD. CONCLUSIONS: We propose three approaches for cluster size determination given the number of clusters for detecting the interaction effect in SW-CRT. GEE and GEE-KC have reasonable operating characteristics for both intermediate and large effect size of HTE.

Rest and exercise-stress estimated pulmonary capillary wedge pressure using real-time free-breathing cardiovascular magnetic resonance imaging.

BACKGROUND: Identification of increased pulmonary capillary wedge pressure (PCWP) by right heart catheterization (RHC) is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF). Recently, cardiovascular magnetic resonance (CMR) imaging estimation of PCWP at rest was introduced as a non-invasive alternative. Since many patients are only identified during physiological exercise-stress, we hypothesized that novel exercise-stress CMR-derived PCWP emerges superior compared to its assessment at rest. METHODS: The HFpEF-Stress Trial prospectively recruited 75 patients with exertional dyspnea and diastolic dysfunction who then underwent rest and exercise-stress RHC and CMR. HFpEF was defined according to PCWP (overt HFpEF ≥15 mmHg at rest, masked HFpEF ≥25 mmHg during exercise-stress). CMR-derived PCWP was calculated based on previously published formula using left ventricular mass and either biplane left atrial volume (LAV) or monoplane left atrial area (LAA). RESULTS: LAV (rest/stress: r = 0.50/r = 0.55, p < 0.001) and LAA PCWP (rest/stress: r = 0.50/r = 0.48, p < 0.001) correlated significantly with RHC-derived PCWP while numerically overestimating PCWP at rest and underestimating PCWP during exercise-stress. LAV and LAA PCWP showed good diagnostic accuracy to detect HFpEF (area under the receiver operating characteristic curve (AUC) LAV rest 0.73, stress 0.81; LAA rest 0.72, stress 0.77) with incremental diagnostic value for the detection of masked HFpEF using exercise-stress (AUC LAV rest 0.54 vs stress 0.67, p = 0.019, LAA rest 0.52 vs stress 0.66, p = 0.012). LAV but not LAA PCWP during exercise-stress was a predictor for 24 months hospitalization independent of a medical history for atrial fibrillation (hazard ratio (HR) 1.26, 95% confidence interval 1.02-1.55, p = 0.032). CONCLUSION: Non-invasive PCWP correlates well with the invasive reference at rest and during exercise stress. There is overall good diagnostic accuracy for HFpEF assessment using CMR-derived estimated PCWP despite deviations in absolute agreement. Non-invasive exercise derived PCWP may particularly facilitate detection of masked HFpEF in the future.

Colonoscopic-assisted laparoscopic wedge resection for colonic neoplasms: a systematic review.

OBJECTIVES: The current literature describes a variety of techniques detailed under the name of combined endoscopic-laparoscopic surgery (CELS) procedures. This systematic review of literature assessed the outcomes of colonoscopic-assisted laparoscopic-wedge resection (CAL-WR) in particular to evaluate its feasibility to remove colonic lesions that do not qualify for endoscopic resection. MATERIALS AND METHODS: Electronic databases (PubMed, Embase, and Cochrane) were searched for studies evaluating CAL-WR for the treatment of colonic lesions. Studies with missing full text, language other than English, systematic reviews, and studies with fewer than ten patients were excluded. The quality of the studies was assessed using the Newcastle-Ottawa Scale. RESULTS: Out of 68 results, duplicate studies (n = 27) as well as studies that did not meet the inclusion criteria (n = 32) were removed. Nine studies were included, encompassing 326 patients who underwent a CAL-WR of the colon. The technical success rate varied from 93 to 100%, with an R0 resection rate of 91-100%. Morbidity ranged from 6% to 20%. The quality of the included studies was rated as low to moderate and contained heterogeneous terminology, methodology, and outcome measures. CONCLUSIONS: There is insufficient high-quality data and substantial variation in outcome measures to draw firm conclusions regarding the value of CAL-WR. Although CAL-WR is a promising local resection technique for endoscopically unremovable neoplasms of the colon, further investigation of this technique in well-designed prospective, multicenter studies with predefined outcome measures is required.Trial registration: A protocol for this systematic review was registered in PROSPERO with the number CRD42023407966.

Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.

Low-density lipoprotein cholesterol-to-lymphocyte count ratio (LLR) is a promising novel predictor of postoperative new-onset deep vein thrombosis following open wedge high tibial osteotomy: a propensity score-matched analysis.

BACKGROUND: The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT. METHODS: Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT. RESULTS: 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size. CONCLUSION: LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.

A stepped-wedge randomised controlled trial to assess efficacy and cost-effectiveness of a care-bundle to prevent falls in older hospitalised patients.

BACKGROUND: Patient accidental falls in a hospital environment are a serious problem for patient safety, and for the additional costs due to associated medical interventions. OBJECTIVE: The endpoints of this study were the assessment of the fall incidence in the hospital before and after the implementation of a multidisciplinary care-bundle, along with a cost-effectiveness evaluation. DESIGN: A stepped-wedge trial was conducted between April 2015 and December 2016 in Bologna University Hospital. METHODS: Incidence rates (IRs) of falls in both the control and intervention periods were calculated. A multilevel mixed-effects generalised linear model with logit link function, adjusted for age, sex, cluster cross-over timing and patients' clinical severity was used to estimate odds ratios (OR) of fall risk of patients of the intervention group respect to the controls.Intervention costs associated with the introduction of the care-bundle intervention were spread between patients per cluster-period-group of exposure. Incremental cost-effectiveness ratio was evaluated using total costs in the intervention and control groups. RESULTS: IRs of falls in control and intervention periods were respectively 3.15 and 2.58 for 1,000 bed-days. After adjustment, the subjects receiving the intervention had a statistically significant reduced risk of falling with respect to those who did not (OR = 0.71, 95% confidence interval: 0.60-0.84). According to the cost-effectiveness analysis, the incremental cost per fall prevented was €873.92 considering all costs, and €1644.45 excluding costs related falls. CONCLUSIONS: Care-bundle had a protective effect on patients, with a statistically significant reduction of the fall risk. This type of intervention appears cost-effective compared to routine practices.

Impact of a prospective feedback loop aimed at reducing non-beneficial treatments in older people admitted to hospital and potentially nearing the end of life. A cluster stepped-wedge randomised controlled trial.

OBJECTIVES: To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life. DESIGN: Prospective stepped-wedge cluster randomised trial with usual care and intervention phases. SETTING: Three large tertiary public hospitals in south-east Queensland, Australia. PARTICIPANTS: 14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84 years) who were potentially near the end of life and flagged at risk of non-beneficial treatment. INTERVENTION: The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35 weeks across the three hospitals. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk. RESULTS: There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03). CONCLUSIONS: This nudge intervention was not sufficient to reduce the trial's non-beneficial treatment outcomes in older hospital patients. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

Readmission after enhanced recovery video-assisted thoracoscopic surgery wedge resection.

BACKGROUND: Despite the implementation of Enhanced Recovery After Surgery (ERAS) programs, surgical stress continues to influence postoperative rehabilitation, including the period after discharge. However, there is a lack of data available beyond the point of discharge following video-assisted thoracoscopic surgery (VATS) wedge resection. Therefore, the objective of this study is to investigate incidence and risk factors for readmissions after ERAS VATS wedge resection. METHODS: A retrospective analysis was performed on data from prospectively collected consecutive VATS wedge resections from June 2019 to June 2022. We evaluated main reasons related to wedge resection leading to 90-day readmission, early (occurring within 0-30 days postoperatively) and late readmission (occurring within 31-90 days postoperatively). To identify predictors for these readmissions, we utilized a logistic regression model for both univariable and multivariable analyses. RESULTS: A total of 850 patients (non-small cell lung cancer 21.5%, metastasis 44.7%, benign 31.9%, and other lung cancers 1.9%) were included for the final analysis. Median length of stay was 1 day (IQR 1-2). During the postoperative 90 days, 86 patients (10.1%) were readmitted mostly due to pneumonia and pneumothorax. Among the cohort, 66 patients (7.8%) had early readmissions primarily due to pneumothorax and pneumonia, while 27 patients (3.2%) experienced late readmissions mainly due to pneumonia, with 7 (0.8%) patients experiencing both early and late readmissions. Multivariable analysis demonstrated that male gender, pulmonary complications, and neurological complications were associated with readmission. CONCLUSIONS: Readmission after VATS wedge resection remains significant despite an optimal ERAS program, with pneumonia and pneumothorax as the dominant reasons. Early readmission was primarily associated with pneumothorax and pneumonia, while late readmission correlated mainly with pneumonia.

Biomechanical effects of cranial closing wedge osteotomy on joint stability in normal canine stifles: an ex vivo study.

BACKGROUND: Cranial closing wedge osteotomy (CCWO) is a functional stabilisation technique for cranial cruciate ligament (CrCL) ruptures. This biomechanical study aimed to evaluate the influence of CCWO on the stability of the stifle joint. Eighteen Beagle stifle joints were divided into two groups: control and CCWO. The stifle joints were analyzed using a six-degree-of-freedom robotic joint biomechanical testing system. The joints were subjected to 30 N in the craniocaudal (CrCd) drawer and proximal compression tests and 1 Nm in the internal-external (IE) rotation test. Each test was performed with an extension position, 135°, and 120° of joint angle. RESULTS: The stifle joints were tested while the CrCLs were intact and then transected. In the drawer test, the CCWO procedure, CrCL transection, and stifle joint flexion increased CrCd displacement. The CCWO procedure and CrCL transection showed an interaction effect. In the compression test, the CCWO procedure decreased and CrCL transection and stifle joint flexion increased displacement. In the IE rotation test, CCWO, CrCL transection, and stifle joint flexion increased the range of motion. CONCLUSIONS: CCWO was expected to provide stability against compressive force but does not contribute to stability in the drawer or rotational tests. In the CCWO-treated stifle joint, instability during the drawer test worsened with CrCL transection. In other words, performing the CCWO procedure when the CrCL function is present is desirable for stabilizing the stifle joint.

Efficient designs for three-sequence stepped wedge trials with continuous recruitment.

BACKGROUND/AIMS: The standard approach to designing stepped wedge trials that recruit participants in a continuous stream is to divide time into periods of equal length. But the choice of design in such cases is infinitely more flexible: each cluster could cross from the control to the intervention at any point on the continuous time-scale. We consider the case of a stepped wedge design with clusters randomised to just three sequences (designs with small numbers of sequences may be preferred for their simplicity and practicality) and investigate the choice of design that minimises the variance of the treatment effect estimator under different assumptions about the intra-cluster correlation. METHODS: We make some simplifying assumptions in order to calculate the variance: in particular that we recruit the same number of participants, m, from each cluster over the course of the trial, and that participants present at regularly spaced intervals. We consider an intra-cluster correlation that decays exponentially with separation in time between the presentation of two individuals from the same cluster, from a value of ρ for two individuals who present at the same time, to a value of ρτ for individuals presenting at the start and end of the trial recruitment interval. We restrict attention to three-sequence designs with centrosymmetry - the property that if we reverse time and swap the intervention and control conditions then the design looks the same. We obtain an expression for the variance of the treatment effect estimator adjusted for effects of time, using methods for generalised least squares estimation, and we evaluate this expression numerically for different designs, and for different parameter values. RESULTS: There is a two-dimensional space of possible three-sequence, centrosymmetric stepped wedge designs with continuous recruitment. The variance of the treatment effect estimator for given ρ and τ can be plotted as a contour map over this space. The shape of this variance surface depends on τ and on the parameter mρ/(1-ρ), but typically indicates a broad, flat region of close-to-optimal designs. The 'standard' design with equally spaced periods and 1:1:1 allocation rarely performs well, however. CONCLUSIONS: In many different settings, a relatively simple design can be found (e.g. one based on simple fractions) that offers close-to-optimal efficiency in that setting. There may also be designs that are robustly efficient over a wide range of settings. Contour maps of the kind we illustrate can help guide this choice. If efficiency is offered as one of the justifications for using a stepped wedge design, then it is worth designing with optimal efficiency in mind.