Cost-effectiveness and willing-to-pay thresholds for vertebral augmentation of osteoporotic vertebral fractures, what are they based on: a systematic review.

OBJECTIVE: Although there is substantial clinical evidence on the safety and effectiveness of vertebral augmentation for osteoporotic vertebral fractures, cost-effectiveness is less well known. The objective of this study is to provide a systematic review of cost-effectiveness studies and policy-based willingness-to-pay (WTP) thresholds for different vertebral augmentation (VA) procedures, vertebroplasty (VP) and balloon kyphoplasty (BK), for osteoporotic vertebral fractures (OVFs). DESIGN: A systematic review targeting cost-effectiveness studies of VA procedures for OVFs. DATA SOURCES: Six bibliographic databases were searched from inception up to May 2021. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Studies were eligible if meeting all predefined criteria: (1) VP or BK intervention, (2) OVFs and (3) cost-effectiveness study. Articles not written in English, abstracts, editorials, reviews and those reporting only cost data were excluded. DATA EXTRACTION AND SYNTHESIS: Information was extracted on study characteristics, cost-effective estimates, summary decisions and payer WTP thresholds. Incremental cost-effective ratio (ICER) was the main outcome measure. Studies were summarised by a structured narrative synthesis organised by comparisons with conservative management (CM). Two independent reviewers assessed the quality (risk of bias) of the systematic review and cost-effectiveness studies by peer-reviewed checklists. RESULTS: We identified 520 references through database searching and 501 were excluded as ineligible by titles and abstract. Ten reports were identified as eligible from 19 full-text reviews. ICER for VP versus CM evaluated as cost per quality-adjusted life-year (QALY) ranged from €22 685 (*US$33 395) in Netherlands to £-2240 (*US$-3273), a cost-saving in the UK. ICERs for BK versus CM ranged from £2706 (*US$3954) in UK to kr600 000 (*US$90 910) in Sweden. ICERs were within payer WTP thresholds for a QALY based on historical benchmarks. CONCLUSIONS: Both VP and BK were judged cost-effective alternatives to CM for OVFs in economic studies and were within WTP thresholds in multiple healthcare settings.

Non-invasive mass and temperature quantifications with spectral CT.

Spectral CT has been increasingly implemented clinically for its better characterization and quantification of materials through its multi-energy results. It also facilitates calculation of physical density, allowing for non-invasive mass measurements and temperature evaluations by manipulating the definition of physical density and thermal volumetric expansion, respectively. To develop spectral physical density quantifications, original and parametrized Alvarez-Macovski model and electron density-physical density model were validated with a phantom. The best physical density model was then implemented on clinical spectral CT scans of ex vivo bovine muscle to determine the accuracy and effect of acquisition parameters on mass measurements. In addition, the relationship between physical density and changes in temperature was evaluated by scanning and subjecting the tissue to a range of temperatures. The parametrized Alvarez-Macovski model performed best in both model development and validation with errors within ± 0.02 g/mL. No effect from acquisition parameters was observed in mass measurements, which demonstrated accuracy with a maximum percent error of 0.34%. Furthermore, physical density was strongly correlated (R of 0.9781) to temperature changes through thermal volumetric expansion. Accurate and precise spectral physical density quantifications enable non-invasive mass measurements for pathological detection and temperature evaluation for thermal therapy monitoring in interventional oncology.

Cost-effectiveness studies of vertebral augmentation for osteoporotic vertebral fractures: a systematic review.

BACKGROUND CONTEXT: Osteoporotic vertebral fractures (OVF) dramatically increase with age and are serious life altering adverse events for seniors resulting in increased rates of institutionalization, morbidity and mortality. Given the expanding population of the elderly and increasing prevalence of OVFs, cost-effective treatment strategies need to be considered. Percutaneous vertebral augmentation (VA) procedures such as vertebroplasty (VP) or balloon kyphoplasty (BK) are increasingly employed to treat painful vertebral fractures not responding to conservative management (CM) of bedrest and analgesia. Both VA procedures have been shown to be effective treatments for OVFs in multiple systematic reviews of randomized controlled trials. In this systematic review, analytical strategies, designs and results were compared for health economic studies evaluating cost-effectiveness of VA procedures, VP or BK for OVFs. Furthermore, assessments of quality (risk of bias) were conducted for the systematic review and the individual studies with peer-reviewed checklists recommended for cost-effectiveness studies. PURPOSE: To provide an up-to-date systematic review of peer-reviewed studies evaluating cost-effectiveness of VA procedures, VP or KP for OVFs to support treatment and health care funding decisions. STUDY DESIGN: This study is a systematic literature review and structured narrative synthesis. STUDY SAMPLE: Peer reviewed health economic studies reporting cost-effectiveness for VA procedures, VP or BK for OVFs OUTCOME MEASURES: The following information extracted from the studies included: report country and year, study design, comparators, population, perspective, health valuations, costing sources and cost-effectiveness measures. For economic studies involving modeling, information was also extracted for model type, time horizon, key model drivers, and handling of uncertainty. Incremental cost-effectiveness ratio (ICER), the ratio of differences between comparator treatment groups in costs and health benefits, was considered the main cost-effectiveness measure. METHODS: A systematic review was conducted of MEDLINE, EMBASE, CINAHL, ECONLIT, Cochrane Library and DARE databases up to the review date May 2021. Studies were reviewed for those reporting cost-effectiveness analyses on VA procedures including VP or BK for OVFs. Studies including only costs, abstracts, editorials, methodologies and reviews were not included. The selection of articles was reported in line with PRISMA guidance. A descriptive framework was developed to classify types of cost-effectiveness studies based on methodological differences and a structured narrative synthesis was used to summarize studies. Quality assessments were made with British Medical Journal checklist for individual cost-effectiveness studies and the CiCERO checklist for systematic reviews of cost-effectiveness studies. RESULTS: In this systematic review, 520 references were identified through database searching and 501 were excluded as ineligible by titles and abstract based on prior eligibility criteria. From full-text reviews of 19 reports, ten were identified as eligible for the systematic review evaluating cost-effectiveness of VA procedures for OVFs. All references were published between 2008 and 2020. The ten cost-effectiveness studies, three for VP, three for BK and four for both VP and BK, all involved CM for OVFs as a treatment comparator. The studies involved different methods of economic analysis, modeling assumptions, cost and health valuations conducted in different health care setting over different time periods. A framework for the review outlines key features of cost-effectiveness study designs consisting of unmatched, matched, or randomized controls involving cost-effectiveness or cost-utility) analyses. Both VP and BK were cost-effective alternatives to CM for OVFs with earlier health gains and significantly shorter hospital stays. Cost-effectiveness estimates, ICERs, remained relatively stable and within willingness-to-pay thresholds under a range of sensitivity analyses. Comparisons between VP and BK were variable depending on modeling assumptions, but generally the procedures had similar health benefit gains with VP having lower acute procedural costs. CONCLUSIONS: Both VP and BK, have been shown to be cost-effective alternatives to CM for osteoporotic vertebral fractures in diverse cost-effectiveness studies conducted in multiple health care settings. Trial-based cost-utility contributed the strongest evidence supporting cost-effectiveness determination for VP and BK for OVFs.

Sepsis Alerts in Emergency Departments: A Systematic Review of Accuracy and Quality Measure Impact.

INTRODUCTION: For early detection of sepsis, automated systems within the electronic health record have evolved to alert emergency department (ED) personnel to the possibility of sepsis, and in some cases link them to suggested care pathways. We conducted a systematic review of automated sepsis-alert detection systems in the ED. METHODS: We searched multiple health literature databases from the earliest available dates to August 2018. Articles were screened based on abstract, again via manuscript, and further narrowed with set inclusion criteria: 1) adult patients in the ED diagnosed with sepsis, severe sepsis, or septic shock; 2) an electronic system that alerts a healthcare provider of sepsis in real or near-real time; and 3) measures of diagnostic accuracy or quality of sepsis alerts. The final, detailed review was guided by QUADAS-2 and GRADE criteria. We tracked all articles using an online tool (Covidence), and the review was registered with PROSPERO registry of reviews. A two-author consensus was reached at the article choice stage and final review stage. Due to the variation in alert criteria and methods of sepsis diagnosis confirmation, the data were not combined for meta-analysis. RESULTS: We screened 693 articles by title and abstract and 20 by full text; we then selected 10 for the study. The articles were published between 2009-2018. Two studies had algorithm-based alert systems, while eight had rule-based alert systems. All systems used different criteria based on systemic inflammatory response syndrome (SIRS) to define sepsis. Sensitivities ranged from 10-100%, specificities from 78-99%, and positive predictive value from 5.8-54%. Negative predictive value was consistently high at 99-100%. Studies showed some evidence for improved process-of-care markers, including improved time to antibiotics. Length of stay improved in two studies. One low quality study showed improved mortality. CONCLUSION: The limited evidence available suggests that sepsis alerts in the ED setting can be set to high sensitivity. No high-quality studies showed a difference in mortality, but evidence exists for improvements in process of care. Significant further work is needed to understand the consequences of alert fatigue and sensitivity set points.

Dosimetric Analysis and Normal-Tissue Complication Probability Modeling of Child-Pugh Score and Albumin-Bilirubin Grade Increase After Hepatic Irradiation.

PURPOSE: This study aimed to develop robust normal-tissue complication probability (NTCP) models for patients with hepatocellular carcinoma treated with radiation therapy (RT) using Child-Pugh (CP) score and albumin-bilirubin (ALBI) grade increase as endpoints for hepatic toxicity. METHODS AND MATERIALS: Data from 108 patients with hepatocellular carcinoma treated with RT between 2008 and 2017 were evaluated, of which 47 patients (44%) were treated with proton RT. Of these patients, 29 received stereotactic body RT and 79 moderately hypofractionated RT to median physical tumor doses of 43 Gy in 5 fractions and 59 Gy in 15 fractions, respectively. A generalized Lyman-Kutcher-Berman (LKB) model was used to model the NTCP using 2 clinical endpoints, both evaluated at 3 months after RT: CP score increase of ≥2 and ALBI grade increase of ≥1 from the pre-RT baseline. Confidence intervals on LKB fit parameters were determined using bootstrap resampling. RESULTS: Compared with previous NTCP models, this study found a stronger correlation between normal liver volume receiving low doses of radiation (5-10 Gy) and a CP score or ALBI grade increase. A CP score increase exhibited a stronger correlation to normal liver volumes irradiated than an ALBI grade increase. LKB models for CP increase found values for the volume-effect parameter of a = 0.06 for all patients, and a = 0.02/0.09 when fit to photon/proton patients separately. Subset analyses for patients with superior initial liver functions showed consistent dose-volume effects (a = 0.1) and consistent dose-response relationships. CONCLUSIONS: This study presents an update of liver NTCP models in the era of modern RT techniques using relevant endpoints of hepatic toxicity, CP score and ALBI grade increase. The results show a stronger influence of low-dose bath on hepatic toxicity than those found in previous studies, indicating that RT techniques that minimize the low-dose bath may be beneficial for patients.

Symptom correlates of dyspnea in advanced cancer patients using the Edmonton Symptom Assessment System.

PURPOSE: Dyspnea is frequently experienced in advanced cancer patients and is associated with poor prognosis and functional decline. This study used the Edmonton Symptom Assessment System (ESAS) to characterize the relationship between dyspnea and concurrent symptoms experienced by advanced cancer patients. METHODS: A prospective database was collected and analyzed to extract patient demographics and ESAS scores. Logistic regression analysis and generalized estimating equations (GEE) identified correlations of other ESAS symptoms in three categories: severity of dyspnea (none, mild, moderate, severe), moderate/severe dyspnea (ESAS ≥ 4), and presence of dyspnea (ESAS ≥ 1), at patients' first visit and over time, respectively. RESULTS: Multivariable analysis revealed drowsiness (p = 0.001), and anxiety (p = 0.01) and appetite loss (p = 0.02) were associated with increased severity of dyspnea at first visit. Over time, tiredness (p = 0.02), drowsiness (p = 0.04), nausea (p = 0.02), and anxiety (p = 0.0006) were more likely to experience increased dyspnea severity. Tiredness (p = 0.0003), depression (p = 0.03), and appetite loss (p = 0.003) were significant for moderate/severe dyspnea at first visit. Over multiple visits, tiredness (p < 0.0001), anxiety (p = 0.0008), and appetite loss (p = 0.0008) had higher probabilities of moderate/severe dyspnea. For the presence of dyspnea at the first visit, anxiety (p = 0.03) and drowsiness (p = 0.002) were significantly correlated with an increased frequency of dyspnea. Over time, anxiety (p < 0.0001) and drowsiness (p < 0.0001) remained significant with the addition of nausea (p = 0.0007). CONCLUSIONS: The highly interactive relationship between dyspnea and other common cancer symptoms necessitates the development of comprehensive symptom assessments and utilization of multimodal management approaches that consider concurrent symptoms for improved identification and treatment of dyspnea.

Re-analysis of symptom clusters in advanced cancer patients attending a palliative outpatient radiotherapy clinic.

BACKGROUND: Cancer patients often present with several concurrent symptoms. There is evidence to suggest that related symptoms can cluster together in stable groups. The present study sought to identify symptom clusters in advanced cancer patients using the Edmonton Symptom Assessment System (ESAS) in a palliative outpatient radiotherapy clinic. METHODS: Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the 9 ESAS items using ESAS scores from each patient's first visit. RESULTS: PCA identified three symptom clusters (cluster 1: depression, anxiety; cluster 2: nausea, dyspnea, loss of appetite; cluster 3: pain, well-being, tiredness, drowsiness). EFA identified two clusters (cluster 1: tiredness, drowsiness, loss of appetite, well-being, pain, nausea, dyspnea; cluster 2: depression, anxiety). HCA identified three symptom clusters (cluster 1: depression, anxiety, pain, well-being; cluster 2: tiredness, drowsiness, dyspnea; cluster 3: nausea, loss of appetite). CONCLUSIONS: Symptom clusters were identified using three analytical methods. The following items were always in the same cluster: depression and anxiety; nausea and appetite loss; well-being and pain; tiredness and drowsiness. Further research in symptom clusters is necessary to advance our understanding of the complex symptom interactions in advanced cancer patients and to determine the most clinically relevant symptom clusters.

Predictors of dyspnea in patients with advanced cancer.

BACKGROUND: More than 70% of patients with advanced cancer experience dyspnea. Dyspnea is predictive of shorter survival and interferes with quality of life (QOL). The present study aimed to identify predictors of the presence and severity of dyspnea in advanced cancer patients. METHODS: A prospective database collected from patients attending a palliative radiotherapy clinic was analyzed for patient demographics, Edmonton Symptom Assessment System (ESAS) scores, Patient-Reported Functional Status (PRFS), history of smoking and respiratory conditions, pulse oximetry readings, and primary cancer site. Using the ESAS shortness of breath item, dyspnea was classified as mild [1-3], moderate [4-6] or severe [7-10]. Logistic regression analysis and generalized estimating equations (GEEs) were used to identify predictors of the severity of dyspnea and presence of moderate/severe dyspnea (ESAS ≥4) at patients' first visit and over time, respectively. RESULTS: A total of 252 patients with dyspnea data were included (median age 71.3 years, 61.5% male, 44.4% had dyspnea) in a demographic analysis. Multivariable analysis showed liver metastases (P=0.01, OR =2.04), a history of respiratory conditions (P=0.03, OR =2.09) and PRFS ≥3 (P=0.03, OR =1.75) were predictive of the severity of dyspnea at the first visit. Analyzed over time, liver metastases (P=0.02, OR =1.80), lymph node metastases (P=0.02, OR =1.79), a history of respiratory conditions (P=0.006, OR =2.50) and pulse oximetry <90 (P=0.003, OR =3.32) were predictive of greater severity of dyspnea symptoms. Patients with multiple radiation treatments in the thorax region were less likely to have severe dyspnea symptoms over time (P=0.01, OR =0.32). Lung metastases (P=0.04, OR =2.03), a history of respiratory conditions (P=0.01, OR =2.60) and PRFS ≥3 (P=0.009, OR =2.30) were predictive of moderate/severe dyspnea at the first visit. Over time, lymph node metastases (P=0.003, OR =2.51), a history of respiratory conditions (P=0.04, OR =2.37) and pulse oximetry <90 (P=0.0004, OR =5.15) were predictive of moderate/severe dyspnea. CONCLUSIONS: Liver, lung and lymph node metastases, a history of respiratory conditions, pulse oximetry <90 and PRFS ≥3 were predictive of the severity of dyspnea and moderate/severe dyspnea. Physicians should be aware of predictive factors that could lead to dyspnea to promote early intervention for improved patient care and the creation of screening tools for clinical practice.

An update in symptom clusters using the Edmonton Symptom Assessment System in a palliative radiotherapy clinic.

PURPOSE: To identify symptom clusters in advanced cancer patients attending a palliative radiotherapy clinic using the Edmonton Symptom Assessment System (ESAS). METHODS: Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items using scores from each patient's first visit. RESULTS: ESAS scores from 182 patients were analyzed. The PCA identified three symptom clusters (cluster 1: depression-anxiety-well-being, cluster 2: pain-tiredness-drowsiness, cluster 3: nausea-dyspnea-loss of appetite). The EFA identified two clusters (cluster 1: tiredness-drowsiness-loss of appetite-well-being-pain-nausea-dyspnea, cluster 2: depression-anxiety). The HCA identified three clusters similar to the PCA with an exception of the loss of appetite item being classified under cluster 1 rather than 3. Two to three symptom clusters were identified using three analytical methods, with similar patterns reported in the literature. Particular groups of items co-occurred consistently across all three analyses: depression and anxiety; nausea and dyspnea; as well as pain, tiredness, and drowsiness. CONCLUSION: Three similar symptom clusters were identified in our patient population using the PCA and HCA; whereas, the EFA produced two clusters: one physical and one psychological cluster. Given the implications of symptom clusters in the management of quality of life, clinicians should be aware of these clusters to aid in the palliative treatment of patients.

Pelvic fractures in children: an exploration of practice patterns and patient outcomes.

Pelvic fractures in children represent a unique set of patients for several reasons. Pediatric pelvic fractures are relatively uncommon and the long-term consequences of these fractures and their associated injuries often have a substantial impact on these patients for the rest of their lives. There is significant controversy regarding the appropriate approach toward the management of these injuries. Nevertheless, there is substantial variability in the orthopaedic management of pediatric pelvic fractures, which warrants a closer investigation. A good starting point for addressing some of these issues is to explore the relationship between practice patterns and patient outcomes. More specifically, a study exploring the relationship between the type of centers that treat these unique fractures and patient outcomes can yield some insightful information. In an effort to address these issues, the authors used the National Pediatric Trauma Registry to conduct a retrospective analysis of this unique pediatric population. The main outcome of interest focused on mortality. With respect to patient information, the independent variables involved demographics (gender, age, race), type of injury (penetrating, blunt, crush), presence of head injury, injury severity indices (Injury Severity Score [ISS], Glasgow Coma Scale), and the Functional Independence Measure. After adjusting for confounding and interaction effects between these variables, only ISS and the type of hospital were determined to be significant in predicting survival.

Use of ketorolac tromethamine in children undergoing scoliosis surgery. an analysis of complications.

BACKGROUND CONTEXT: Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti-inflammatory drug (NSAID) with proven efficacy in decreasing postoperative pain in various surgical settings, including the treatment of spine deformities. However, some studies have raised questions regarding the potential side effects of this agent, such as increased bleeding and inhibition of bony fusion. PURPOSE: This study was conducted to determine whether there is any association between the use of ketorolac and postoperative complications in a group of children who underwent scoliosis surgery. STUDY DESIGN/SETTING: This is a retrospective review of a group of children who underwent spinal fusion between 1989 to 1999 at our institution. PATIENT SAMPLE: Data on a total of 208 children were analyzed in this study. Sixty received ketorolac and 148 did not. OUTCOME MEASURES: Postoperative transfusion and reoperation rates were the two main outcome measures of interest. METHODS: A retrospective review of 208 children who underwent scoliosis surgery was conducted, with a focus on ketorolac use. Univariate analysis and logistic regression were used to quantify the determinants of postoperative complications. RESULTS: Our analyses detected no significant differences in a broad range of socioclinical variables between the two patient groups, including age at surgery, gender, type of scoliosis, surgical approach, use of erythropoietin, levels of curvature and degree of curvature. Analysis of complication rates focusing on postoperative transfusion and revision surgery showed that there were no significant differences between the two groups. CONCLUSIONS: In this retrospective study of 208 children undergoing spine surgery, postoperative use of ketorolac did not significantly increase complications, including transfusion and reoperation.