Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer.

PURPOSE: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. METHODS: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center's adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. CONCLUSION: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641).

The challenge of sustainability in healthcare systems: cost of radiotherapy in the last month of life in an Italian cancer center.

PURPOSE: Cost evaluation is becoming mandatory to support healthcare sustainability and optimize the decision-making process. This topic is a challenge, especially for complex and rapidly evolving treatment modalities such as radiotherapy (RT). The aim of the present study was to investigate the cost of RT in the last month of life of patients in an Italian cancer center. METHODS: This was a retrospective study on a cancer population (N= 160) who underwent RT or only an RT planning simulation in an end of life (EOL) setting. The cost of RT procedures performed on patients was collected according to treatment status, care setting, and RT technique used. Costs were valued according to the sum of reimbursements relating to all procedures performed and assessed from the perspective of the National Health System. RESULTS: The total cost of RT in the last month of life was €244,774, with an average cost per patient of €1530. Around 7.7% and 30.3% of the total cost was associated with patients who never started RT or who discontinued RT, respectively, while the remaining 62.0% referred to patients who completed treatment. Costs associated with outpatient and inpatient settings represented 54.3% and 38.6% of the total cost, respectively. The higher average cost per patient for the never-started and discontinued groups was correlated with patients who had a poor ECOG Performance Status. CONCLUSION: Improved prognostic accuracy and a better integration between radiotherapy and palliative care units could be a key to a better use of resources and to a reduction in the cost of EOL RT.

Effect of the In Vitro Boundary Conditions on the Surface Strain Experienced by the Vertebral Body in the Elastic Regime.

The vertebral strength and strain can be assessed in vitro by both using isolated vertebrae and sets of three adjacent vertebrae (the central one is loaded through the disks). Our goal was to elucidate if testing single-vertebra-specimens in the elastic regime provides different surface strains to three-vertebrae-segments. Twelve three-vertebrae sets were extracted from thoracolumbar human spines. To measure the principal strains, the central vertebra of each segment was prepared with eight strain-gauges. The sets were tested mechanically, allowing comparison of the surface strains between the two boundary conditions: first when the same vertebra was loaded through the disks (three-vertebrae-segment) and then with the endplates embedded in cement (single-vertebra). They were all subjected to four nondestructive tests (compression, traction, torsion clockwise, and counterclockwise). The magnitude of principal strains differed significantly between the two boundary conditions. For axial loading, the largest principal strains (along vertebral axis) were significantly higher when the same vertebra was tested isolated compared to the three-vertebrae-segment. Conversely, circumferential strains decreased significantly in the single vertebrae compared to the three-vertebrae-segment, with some variations exceeding 100% of the strain magnitude, including changes from tension to compression. For torsion, the differences between boundary conditions were smaller. This study shows that, in the elastic regime, when the vertebra is loaded through a cement pot, the surface strains differ from when it is loaded through the disks. Therefore, when single vertebrae are tested, surface strain should be taken with caution.

Endometriosis and endometrial cancer: A propensity score-adjusted real-world data study.

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40-1.73, p < 0.001). Women with endometriosis were more likely to develop invasive endometrioid (p = 0.005) and clear cell (p < 0.001) EC. There was no difference in overall survival between endometriosis-associated EC and EC without endometriosis. Our epidemiological findings were consistent with the evidence of an association between endometriosis and EC.

Healthcare Costs and Resource Utilisation of Italian Metastatic Non-Small Cell Lung Cancer Patients.

This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population.

How has COVID-19 pandemic changed flu vaccination attitudes among an Italian cancer center healthcare workers?

A retrospective study was conducted among Italian cancer healthcare workers (HCWs) to describe how influenza vaccination attitudes have changed during the COVID-19 pandemic. The analysis was conducted on the last three influenza seasons (2018/19, 2019/20 and 2020/21). To account for different relationships and proximity with patients, the study population was grouped into three main professional categories: health personnel, administrative staff and technicians. Moreover, to explore the factors affecting the coverage of influenza vaccine, a multinomial regression analysis was performed.Over the years, the influenza vaccination uptake showed a gradual increase across the overall staff, the highest coverage (53.8%) was observed in the season 2020/21, in particular, for health personnel (57.7%). In general, males resulted in more adherent to vaccination campaigns; nevertheless, this gap decreased in the last season. A total of 28.6% workers were always vaccinated throughout the past three seasons, a remarkable 25.2% (mainly young and females) received for the first time the influenza vaccination in 2020/21.In this dramatic health crisis, the attitudes of HCWs toward flu vaccination have changed. The COVID-19 outbreak increased adherence to flu vaccination, reaching the highest coverage in the campaign 2020/21. However, further efforts should be made to achieve greater vaccination coverage.

Real-World Outcomes and Treatments Patterns Prior and after the Introduction of First-Line Immunotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: This study provides insights into the treatment use and outcomes of metastatic non-small cell lung cancer (NSCLC) patients in a real-world setting prior to and after the availability of immuno-oncology (IO) regimens in the first line (1L). METHODS: Metastatic NSCLC patients, who initiated systemic 1L anticancer treatment from 2014 to 2020, were identified from health records. Patients were grouped into Pre-1L IO and Post-1L IO, according to the availability of pembrolizumab 1L monotherapy at the date of initiating 1L systemic anticancer treatment. Patient characteristics, treatment patterns and outcomes were assessed by the cohort. Overall survival (OS) and real-world progression-free survival (rwPFS) were calculated using the Kaplan-Meier method. RESULTS: The most common 1L treatment was platinum-based chemotherapy regimens in both groups (≥46%), followed by single-agent chemotherapy (27.0%) in Pre-1L IO and pembrolizumab (26.0%) in Post-1L IO. Median OS was 6.2 (95% CI 5.5-7.4) in Pre- and 8.9 months (95% CI 7.5-10.6) in Post-1L IO, while rwPFS was 3.7 (95% CI 3.3-4.2) and 4.7 months (95% CI 3.9-5.7), respectively. CONCLUSIONS: Even if a small proportion of patients received a 1L IO, the data showed an improved survival outcomes in the Post-1L IO group.

How to discriminate non-small cell lung cancer (NSCLC) cases from an Italian administrative database? A retrospective, secondary data use study for evaluating a novel algorithm performance.

OBJECTIVES: To evaluate an algorithm developed for identifying non-small cell lung cancer (NSCLC) candidates among patients with lung cancer with a diagnosis International Classification of Diseases: ninth revision (ICD-9) 162.x code in administrative databases. Algorithm could then be applied for identifying the NSCLC population in order to assess the appropriateness and quality of care of the NSCLC care pathway. DESIGN: Algorithm discrimination capacity to select both NSCLC or non-NSCLC was carried out on a sample for which electronic health record (EHR) diagnosis was available. A bivariate frequency distribution and other measures were used to evaluate algorithm's performances. Associations between possible factors potentially affecting algorithm accuracy were investigated. SETTING: Administrative databases used in a specific geographical area of Emilia-Romagna region, Italy. PARTICIPANTS: Algorithm was carried out on patients aged >18 years, with a lung cancer diagnosis from January to December 2017 and resident in Emilia-Romagna region who have been hospitalised at IRST or in one of the hospitals placed in the Forlì-Cesena area and for which EHR diagnosis data were available. OUTCOME MEASURES: Overall accuracy, positive (PPV) and negative (NPV) predictive values, sensitivity and specificity, positive and negative likelihood ratios and diagnostic OR were calculated. RESULTS: A total of 430 patients were identified as lung cancer cases based on ICD-9 diagnosis. Focusing on the total incident cases (n=314), the algorithm had an overall accuracy of 82.8% with a sensitivity of 88.8%. The analysis confirmed a high level of PPV (90.2%), but lower specificity (53.7%) and NPV (50%). Higher length of stay seemed to be associated with a correct classification. Hospitalisation regimen and a supply of antiblastic therapy seemed to increase the level of PPV. CONCLUSION: The algorithm demonstrated a strong validity for identifying NSCLC among patients with lung cancer in hospital administrative databases and can be used to investigate the quality of cancer care for this population. TRIAL REGISTRATION NUMBER: NCT04676321.

Radiology imaging management in an Italian cancer center (IRST IRCCS) during the COVID-19 pandemic.

In Italy, the first case of the coronavirus disease 2019 (COVID-19) was officially reported on 20.02.2020. The disease has since rapidly evolved, causing a public health emergency throughout the country but especially in our region, one of the most widely affected areas. We reorganized the daily routine of our cancer center to reduce the risk of contagion. A temporary tensile structure was set up as an entry-point triage, and a COVID-19 route was created with a dedicated CT scanner. A pre-access telephonic triage was performed the day before a patient was scheduled to come in for an examination. At the time of writing (May 4), 4053 patients had been to our center since the emergency officially began (9.03.2020) and the COVID-19 route had been activated for only 9 paucisymptomatic outpatients and 7 symptomatic inpatients. We also re-evaluated patient radiology examination lists and rescheduled non-urgent tests in consensus with the referring oncologist. Out of a total of 1438 patients scheduled for radiological examinations, 456 were postponed for a total volume reduction of 29.1%. Nine asymptomatic patients with typical CT findings of COVID-19 were identified during routine CTs, but none were RT-PCR-positive for SARS-CoV-2. We guaranteed all urgent and semi-urgent examinations, including those to stage newly diagnosed cancers and to evaluate response to treatment, ensuring the continuation of the diagnostic and therapeutic pathway of our patients. The measures we took were instrumental in keeping the institute COVID-19-free. We also describe the planned measures to resume normal clinical practice at the center.

Micro Finite Element models of the vertebral body: Validation of local displacement predictions.

The estimation of local and structural mechanical properties of bones with micro Finite Element (microFE) models based on Micro Computed Tomography images depends on the quality bone geometry is captured, reconstructed and modelled. The aim of this study was to validate microFE models predictions of local displacements for vertebral bodies and to evaluate the effect of the elastic tissue modulus on model's predictions of axial forces. Four porcine thoracic vertebrae were axially compressed in situ, in a step-wise fashion and scanned at approximately 39µm resolution in preloaded and loaded conditions. A global digital volume correlation (DVC) approach was used to compute the full-field displacements. Homogeneous, isotropic and linear elastic microFE models were generated with boundary conditions assigned from the interpolated displacement field measured from the DVC. Measured and predicted local displacements were compared for the cortical and trabecular compartments in the middle of the specimens. Models were run with two different tissue moduli defined from microindentation data (12.0GPa) and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction forces was compared to the experimental values for each specimen. MicroFE models predicted more than 87% of the variation in the displacement measurements (R2 = 0.87-0.99). However, model predictions of axial forces were largely overestimated (80-369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10-80% were found for a back-calculated tissue modulus. The specimen with the lowest density showed a large number of elements strained beyond yield and the highest predictive errors. This study shows that the simplest microFE models can accurately predict quantitatively the local displacements and qualitatively the strain distribution within the vertebral body, independently from the considered bone types.

Application of digital volume correlation to study the efficacy of prophylactic vertebral augmentation.

BACKGROUND: Prophylactic augmentation is meant to reinforce the vertebral body, but in some cases it is suspected to actually weaken it. Past studies only investigated structural failure and the surface strain distribution. To elucidate the failure mechanism of the augmented vertebra, more information is needed about the internal strain distribution. This study aims to measure, for the first time, the full-field three-dimensional strain distribution inside augmented vertebrae in the elastic regime and to failure. METHODS: Eight porcine vertebrae were prophylactically-augmented using two augmentation materials. They were scanned with a micro-computed tomography scanner (38.8µm voxel resolution) while undeformed, and loaded at 5%, 10%, and 15% compressions. Internal strains (axial, antero-posterior and lateral-lateral components) were computed using digital volume correlation. FINDINGS: For both augmentation materials, the highest strains were measured in the regions adjacent to the injected cement mass, whereas the cement-interdigitated-bone was less strained. While this was already visible in the elastic regime (5%), it was a predictor of the localization of failure, which became visible at higher degrees of compression (10% and 15%), when failure propagated across the trabecular bone. Localization of high strains and failure was consistent between specimens, but different between the cement types. INTERPRETATION: This study indicated the potential of digital volume correlation in measuring the internal strain (elastic regime) and failure in augmented vertebrae. While the cement-interdigitated region becomes stiffer (less strained), the adjacent non-augmented trabecular bone is affected by the stress concentration induced by the cement mass. This approach can help establish better criteria to improve vertebroplasty.

Digital volume correlation can be used to estimate local strains in natural and augmented vertebrae: An organ-level study.

Digital Volume Correlation (DVC) has become popular for measuring the strain distribution inside bone structures. A number of methodological questions are still open: the reliability of DVC to investigate augmented bone tissue, the variability of the errors between different specimens of the same type, the distribution of measurement errors inside a bone, and the possible presence of preferential directions. To address these issues, five augmented and five natural porcine vertebrae were subjected to repeated zero-strain micro-CT scan (39µm voxel size). The acquired images were processed with two independent DVC approaches (a local and a global one), considering different computation sub-volume sizes, in order to assess the strain measurement uncertainties. The systematic errors generally ranged within ±100 microstrain and did not depend on the computational sub-volume. The random error was higher than 1000 microstrain for the smallest sub-volume and rapidly decreased: with a sub-volume of 48 voxels the random errors were typically within 200 microstrain for both DVC approaches. While these trends were rather consistent within the sample, two individual specimens had unpredictably larger errors. For this reason, a zero-strain check on each specimen should always be performed before any in-situ micro-CT testing campaign. This study clearly shows that, when sufficient care is dedicated to preliminary methodological work, different DVC computation approaches allow measuring the strain with a reduced overall error (approximately 200 microstrain). Therefore, DVC is a viable technique to investigate strain in the elastic regime in natural and augmented bones.

Reproducible reference frame for in vitro testing of the human vertebrae.

Definition of an anatomical reference frame is necessary for in vitro biomechanical testing. Nevertheless, there is neither a clear recommendation, nor consensus in the literature concerning an anatomical reference frame for in vitro testing of the human vertebrae. The scope of this work is to define a reference frame for the human vertebrae for in vitro applications. The proposed anatomical reference frame relies on alignment of well-defined points on the endplates, and on two landmarks on the posterior wall. The repeatability of the proposed alignment procedure has been tested in vitro by 5 operators, on 7 specimens. Furthermore, the feasibility and repeatability of the proposed procedure was assessed in silico, using CT-scans of the same specimens. Variations between operators were slightly larger than between repetitions by the same operator. The intra-operator in vitro repeatability was better than 3° for all angles. The inter-operator in vitro repeatability was better than 9° for all angles. The lateral tilt was the most repeatable angle, while anterior-posterior tilt was least repeatable. The repeatability when alignment was performed in silico on CT-scans was comparable to that obtained in vitro, on the physical specimens. This is the first time than an anatomical reference frame is formally defined and validated for the human vertebrae. The adoption of this reference frame will provide more reproducible alignment of the specimens and of the test load. This will enable better in vitro biomechanical tests, and comparisons with numerical models.

Strain distribution in the lumbar vertebrae under different loading configurations.

BACKGROUND CONTEXT: The stress/strain distribution in the human vertebrae has seldom been measured, and only for a limited number of loading scenarios, at few locations on the bone surface. PURPOSE: This in vitro study aimed at measuring how strain varies on the surface of the lumbar vertebral body and how such strain pattern depends on the loading conditions. METHODS: Eight cadaveric specimens were instrumented with eight triaxial strain gauges each to measure the magnitude and direction of principal strains in the vertebral body. Each vertebra was tested in a three adjacent vertebrae segment fashion. The loading configurations included a compressive force aligned with the vertebral body but also tilted (15°) in each direction in the frontal and sagittal planes, a traction force, and torsion (both directions). Each loading configuration was tested six times on each specimen. RESULTS: The strain magnitude varied significantly between strain measurement locations. The strain distribution varied significantly when different loading conditions were applied (compression vs. torsion vs. traction). The strain distribution when the compressive force was tilted by 15° was also significantly different from the axial compression. Strains were minimal when the compressive force was applied coaxial with the vertebral body, compared with all other loading configurations. Also, strain was significantly more uniform for the axial compression, compared with all other loading configurations. Principal strains were aligned within 19° to the axis of the vertebral body for axial-compression and axial-traction. Conversely, when the applied force was tilted by 15°, the direction of principal strain varied by a much larger angle (15° to 28°). CONCLUSIONS: This is the first time, to our knowledge, that the strain distribution in the vertebral body is measured for such a variety of loading configurations and a large number of strain sensors. The present findings suggest that the structure of the vertebral body is optimized to sustain compressive forces, whereas even a small tilt angle makes the vertebral structure work under suboptimal conditions.

Re-use of explanted osteosynthesis devices: a reliable and inexpensive reprocessing protocol.

INTRODUCTION: Orthopaedic surgical treatments emphasizing immobilization using open reduction and internal fixation with osteosynthesis devices are widely accepted for their efficacy in treating complex fractures and reducing permanent musculoskeletal deformity. However, such treatments are profoundly underutilized in low- and middle-income countries (LMIC), partially due to inadequate availability of the costly osteosynthesis devices. Orthopaedic surgeons in some LMIC regularly re-use osteosynthesis devices in an effort to meet treatment demands, even though such devices typically are regulated for single-use only. The purpose of this study is to report a reprocessing protocol applied to explanted osteosynthesis devices obtained at a leading trauma care hospital. METHODS: Explanted osteosynthesis devices were identified through a Register of Explanted Orthopaedic Prostheses. Guidelines to handle ethical issues were approved by the local Ethical Committee and informed patient consent was obtained at the time of explant surgery. Primary acceptance criteria were established and applied to osteosynthesis devices explanted between 2005 and 2008. A rigorous protocol for conducting decontamination and visual inspection based on specific screening criteria was implemented using simple equipment that is readily available in LMIC. RESULTS: A total of 2050 osteosynthesis devices, including a large variety of plates, screws and staples, were reprocessed using the decontamination and inspection protocols. The acceptance rate was 66%. Estimated labour time and implementation time of the protocol to reprocess a typical osteosynthesis unit (1 plate and 5 screws) was 25 min, with an estimated fixed cost (in Italy) of €10 per unit for implementing the protocol, plus an additional €5 for final sterilization at the end-user hospital site. DISCUSSION: This study was motivated by the treatment demands encountered by orthopaedic surgeons providing medical treatment in several different LMIC and their need for access to basic osteosynthesis devices. The rigorous decontamination protocol and generalized inspection criteria proved useful for efficiently screening a large volume of devices. Given that re-used osteosynthesis devices can yield satisfactory results, this study addresses potential complications of re-used devices and valid concerns that relate to patient safety. Implementing this defined reprocessing protocol into existing re-use practises in LMIC helps to limit the risks of inadequate sterilization and structural failure without adding additional risks to patients receiving re-used devices.