Differential Utility Losses in Herpes Zoster Cases Between Vaccinated and Unvaccinated Subjects: A Meta-analysis of Three Clinical Trials.

BACKGROUND AND OBJECTIVE: Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials. METHODS: Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models. RESULTS: The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group. CONCLUSIONS: Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.

Herpes zoster, also known as shingles, may cause painful rashes and persistent pain for months or even years after the initial episode. Recombinant zoster vaccine is approved for the prevention of shingles. Pivotal recombinant zoster vaccine clinical trials have reported data about the impact of shingles episodes on daily activities and overall health-related quality of life. In this work, we combined data from three recombinant zoster vaccine clinical trials and compared the loss in quality of life­measured in quality-adjusted life-years­incurred by vaccinated and unvaccinated subjects who experienced a shingles episode. We found that vaccinated patients experienced lower quality-adjusted life-year losses when they developed shingles compared with unvaccinated patients. Our results may be useful in assessing quality-adjusted life-year losses between vaccinated and unvaccinated cohorts in future herpes zoster vaccination health economics analyses.

Patient-centric Comparability Assessment of Biopharmaceuticals.

The comparability assessment of a biological product after implementing a manufacturing process change should involve a risk-based approach. Process changes may occur at any stage of the product lifecycle: early development, clinical manufacture for pivotal trials, or post-approval. The risk of the change to impact product quality varies. The design of the comparability assessment should be adapted accordingly. A working group reviewed and consolidated industry approaches to assess comparability of traditional protein-based biological products during clinical development and post-approval. The insights compiled in this review article encompass topics such as a risk-evaluation strategy, the design of comparability studies, definition of assessment criteria for comparability, holistic evaluation of data, and the regulatory submission strategy. These practices can be leveraged across the industry to help companies in design and execution of comparability assessments, and to inform discussions with global regulators.

Helping reviewers assess statistical analysis: A case study from analytic methods.

Analytic methods development, like many other disciplines, relies on experimentation and data analysis. Determining the contribution of a paper or report on a study incorporating data analysis is typically left to the reviewer's experience and good sense, without reliance on structured guidelines. This is amplified by the growing role of machine learning driven analysis, where results are based on computer intensive algorithm applications. The evaluation of a predictive model where cross validation was used to fit its parameters adds challenges to the evaluation of regression models, where the estimates can be easily reproduced. This lack of structure to support reviews increases uncertainty and variability in reviews. In this paper, aspects of statistical assessment are considered. We provide checklists for reviewers of applied statistics work with a focus on analytic method development. The checklist covers six aspects relevant to a review of statistical analysis, namely: (1) study design, (2) algorithmic and inferential methods in frequentism analysis, (3) Bayesian methods in Bayesian analysis (if relevant), (4) selective inference aspects, (5) severe testing properties and (6) presentation of findings. We provide a brief overview of these elements providing references for a more elaborate treatment. The robustness analysis of an analytical method is used to illustrate how an improvement can be achieved in response to questions in the checklist. The paper is aimed at both engineers and seasoned researchers.

To tolerate or to agree: A tutorial on tolerance intervals in method comparison studies with BivRegBLS R Package.

The well-known agreement interval by Bland and Altman is extensively applied in method comparison studies. Two clinical measurement methods are considered interchangeable if their differences are not clinically significant. The agreement interval is commonly applied to assess the spread of the differences. However, this interval is approximate (too narrow) and several authors propose calculating a confidence interval around each bound. This article demonstrates that this approach is misleading, awkward, and confusing. On the other hand, tolerance intervals are exact and can include a confidence level if needed. Tolerance intervals are also easier to calculate and to interpret. Real data sets are used to illustrate the tolerance intervals with the R package BivRegBLS under normal or log-normal assumptions. Furthermore, it is also explained how to assess the coverage probabilities of the tolerance intervals with simulations.

Confidence, prediction, and tolerance in linear mixed models.

The literature about Prediction Interval (PI) and Tolerance Interval (TI) in linear mixed models is usually developed for specific designs, which is a main limitation to their use. This paper proposes to reformulate the two-sided PI to be generalizable under a wide variety of designs (one random factor, nested and crossed designs for multiple random factors, and balanced or unbalanced designs). This new methodology is based on the Hessian matrix, namely, the inverse of (observed) Fisher Information matrix, and is built with a cell mean model. The degrees of freedom for the total variance are calculated with the generalized Satterthwaite method and compared to the Kenward-Roger's degrees of freedom for fixed effects. Construction of two-sided TIs are also detailed with one random factor, and two nested and two crossed random variables. An extensive simulation study is carried out to compare the widths and coverage probabilities of Confidence Intervals (CI), PIs, and TIs to their nominal levels. It shows excellent coverage whatever the design and the sample size are. Finally, these CIs, PIs, and TIs are applied to two real data sets: one from orthopedic surgery study (intralesional resection risk) and the other from assay validation study during vaccine development.

Pedicle screw insertion accuracy in terms of breach and reposition using a new intraoperative cone beam computed tomography imaging technique and evaluation of the factors associated with these parameters of accuracy: a series of 695 screws.

PURPOSE: The goals of this study were to assess the accuracy of pedicle screw insertion using an intraoperative cone beam computed tomography (CBCT) system, and to analyze the factors potentially influencing this accuracy. METHODS: Six hundred and ninety-five pedicle screws were inserted in 118 patients between October 2013 and March 2016. Screw insertion was performed using 2D-fluoroscopy or CBCT-based navigation. Accuracy was assessed in terms of breach and reposition. All the intraoperative CBCT scans, done after screw insertion, were reviewed to assess the accuracy of screw placement using two established classification systems: Gertzbein and Heary. Generalized linear mixed models were used to model the odds (95% CI) for a screw to lead to a breach according to the independent variables. RESULTS: The breach rate was 11.7% using the Gertzbein classification and 15.4% using the Heary classification. Seventeen screws (2.4%) were repositioned intraoperatively. The only factor affecting statistically the odds to have a breach was the indication of surgery. The patients with non-degenerative disease had a significantly higher risk of breach than those with degenerative disease. CONCLUSION: Use of intraoperative CBCT as 2D-fluoroscopy or coupled with a navigation system for pedicle screw insertion is accurate in terms of breach occurrence and reposition. However, these rates depend on the classification or grading system used. Use of a navigation system does not decrease the risk of breach significantly. And the risk of breach is higher in non-degenerative conditions (trauma, scoliosis, infection, and malignancy disease) than in degenerative diseases.

Accuracy of a new intraoperative cone beam CT imaging technique (Artis zeego II) compared to postoperative CT scan for assessment of pedicle screws placement and breaches detection.

PURPOSE: The goal of this study was to compare the accuracy of a novel intraoperative cone beam computed tomography (CBCT) imaging technique with that of conventional computed tomography (CT) scans for assessment of pedicle screw placement and breach detection. METHODS: Three hundred and forty-eight pedicle screws were inserted in 58 patients between October 2013 and March 2016. All patients had an intraoperative CBCT scan and a conventional CT scan to verify the placement of the screws. The CBCT and CT images were reviewed by two surgeons to assess the accuracy of screw placement and detect pedicle breaches using two established classification systems. Agreement on screw placement between intraoperative CBCT and postoperative CT was assessed using Kappa and Gwet's coefficients. Using CT scanning as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the ability of CBCT imaging to accurately evaluate screw placement. RESULTS: The Kappa coefficient was 0.78 using the Gertzbein classification and 0.80 using the Heary classification, indicating a substantial agreement between the intraoperative CBCT and postoperative CT images. Gwet's coefficient was 0.94 for both classifications, indicating almost perfect agreement. The sensitivity, specificity, positive predictive value and negative predictive value of the CBCT images were 77, 98, 86, and 96%, respectively, for the Gertzbein classification and 79, 98, 88, and 96%, respectively, for the Heary classification. CONCLUSIONS: Intraoperative CBCT provides accurate assessment of pedicle screw placement and enables intraoperative repositioning of misplaced screws. This technique may make postoperative CT imaging unnecessary.

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration.

BACKGROUND: The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. STUDY DESIGN: Randomized patient-blinded crossover trial. SETTINGS & PARTICIPANTS: 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. INTERVENTION: 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. OUTCOMES: Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. MEASUREMENTS: Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. RESULTS: There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P=0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P<0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P=0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3g/dL; P<0.001). Health-related quality-of-life scores were equivalent. LIMITATIONS: Single center; mean achieved HDF convection volume, 20.6L. CONCLUSIONS: Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Delta method and bootstrap in linear mixed models to estimate a proportion when no event is observed: application to intralesional resection in bone tumor surgery.

Resecting bone tumors requires good cutting accuracy to reduce the occurrence of local recurrence. This issue is considerably reduced with a navigated technology. The estimation of extreme proportions is challenging especially with small or moderate sample sizes. When no success is observed, the commonly used binomial proportion confidence interval is not suitable while the rule of three provides a simple solution. Unfortunately, these approaches are unable to differentiate between different unobserved events. Different delta methods and bootstrap procedures are compared in univariate and linear mixed models with simulations and real data by assuming the normality. The delta method on the z-score and parametric bootstrap provide similar results but the delta method requires the estimation of the covariance matrix of the estimates. In mixed models, the observed Fisher information matrix with unbounded variance components should be preferred. The parametric bootstrap, easier to apply, outperforms the delta method for larger sample sizes but it may be time costly. Copyright © 2016 John Wiley & Sons, Ltd.

How to regress and predict in a Bland-Altman plot? Review and contribution based on tolerance intervals and correlated-errors-in-variables models.

Two main methodologies for assessing equivalence in method-comparison studies are presented separately in the literature. The first one is the well-known and widely applied Bland-Altman approach with its agreement intervals, where two methods are considered interchangeable if their differences are not clinically significant. The second approach is based on errors-in-variables regression in a classical (X,Y) plot and focuses on confidence intervals, whereby two methods are considered equivalent when providing similar measures notwithstanding the random measurement errors. This paper reconciles these two methodologies and shows their similarities and differences using both real data and simulations. A new consistent correlated-errors-in-variables regression is introduced as the errors are shown to be correlated in the Bland-Altman plot. Indeed, the coverage probabilities collapse and the biases soar when this correlation is ignored. Novel tolerance intervals are compared with agreement intervals with or without replicated data, and novel predictive intervals are introduced to predict a single measure in an (X,Y) plot or in a Bland-Atman plot with excellent coverage probabilities. We conclude that the (correlated)-errors-in-variables regressions should not be avoided in method comparison studies, although the Bland-Altman approach is usually applied to avert their complexity. We argue that tolerance or predictive intervals are better alternatives than agreement intervals, and we provide guidelines for practitioners regarding method comparison studies. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial.

AIMS: To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status. METHODS AND RESULTS: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07-1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13-1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23-1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68-0.94 and HR 0.84, 95% CI, 0.75-0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. CONCLUSIONS: Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.

Diagnostic accuracy of the Thessaly test, standardised clinical history and other clinical examination tests (Apley's, McMurray's and joint line tenderness) for meniscal tears in comparison with magnetic resonance imaging diagnosis.

BACKGROUND: Reliable non-invasive diagnosis of meniscal tears is difficult. Magnetic resonance imaging (MRI) is often used but is expensive and incidental findings are problematic. There are a number of physical examination tests for the diagnosis of meniscal tears that are simple, cheap and non-invasive. OBJECTIVES: To determine the diagnostic accuracy of the Thessaly test and to determine if the Thessaly test (alone or in combination with other physical tests) can obviate the need for further investigation by MRI or arthroscopy for patients with a suspected meniscal tear. DESIGN: Single-centre prospective diagnostic accuracy study. SETTING: Although the study was performed in a secondary care setting, it was designed to replicate the results that would have been achieved in a primary care setting. PARTICIPANTS: Two cohorts of patients were recruited: patients with knee pathology (n = 292) and a control cohort with no knee pathology (n = 75). MAIN OUTCOME MEASURES: Sensitivity, specificity and diagnostic accuracy of the Thessaly test in determining the presence of meniscal tears. METHODS: Participants were assessed by both a primary care clinician and a musculoskeletal clinician. Both clinicians performed the Thessaly test, McMurray's test, Apley's test, joint line tenderness test and took a standardised clinical history from the patient. RESULTS: The Thessaly test had a sensitivity of 0.66, a specificity of 0.39 and a diagnostic accuracy of 54% when utilised by primary care clinicians. This compared with a sensitivity of 0.62, a specificity of 0.55 and diagnostic accuracy of 59% when used by musculoskeletal clinicians. The diagnostics accuracy of the other tests when used by primary care clinicians was 54% for McMurray's test, 53% for Apley's test, 54% for the joint line tenderness test and 55% for clinical history. For primary care clinicians, age and past history of osteoarthritis were both significant predictors of MRI diagnosis of meniscal tears. For musculoskeletal clinicians age and a positive diagnosis of meniscal tears on clinical history taking were significant predictors of MRI diagnosis. No physical tests were significant predictors of MRI diagnosis in our multivariate models. The specificity of MRI diagnosis was tested in subgroup of patients who went on to have a knee arthroscopy and was found to be low [0.53 (95% confidence interval 0.28 to 0.77)], although the sensitivity was 1.0. CONCLUSIONS: The Thessaly test was no better at diagnosing meniscal tears than other established physical tests. The sensitivity, specificity and diagnostic accuracy of all physical tests was too low to be of routine clinical value as an alternative to MRI. Caution needs to be exercised in the indiscriminate use of MRI scanning in the identification of meniscal tears in the diagnosis of the painful knee, due to the low specificity seen in the presence of concomitant knee pathology. Further research is required to determine the true diagnostic accuracy and cost-effectiveness of MRI for the detection of meniscal tears. TRIAL REGISTRATION: Current Controlled Trial ISRCTN43527822. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Normal limits of the electrocardiogram in Indians.

AIMS: The objective of the study was to develop normal limits of the ECG in an apparently healthy population of South Asians living in India. METHODS: Three centres contributed to recording 12 lead ECGs on identical digital electrocardiographs. Apparently healthy volunteers were recruited and ECGs were first transferred to a local database and then to Glasgow where all ECGs were analysed by the same University of Glasgow ECG Interpretation Program. RESULTS: A total of 963 individuals were recruited into the study (30.4% female) with an age range of 18-83 years. QRS duration was longer in males than females, QT interval was longer in females than males, and QRS voltages in general were higher in males than females and in younger compared to older individuals. CONCLUSION: Findings in general paralleled those in other populations and suggested that criteria for a white Caucasian population could be applied to a South Asian Indian population.

Local complications of massive bone allografts: an appraisal of their prevalence in 128 patients.

Bone allografts were used in our department since twenty-five years to reconstruct segmental bone loss and our data were retrospectively reviewed to assess the complications related to the use of a bone allograft. A consecutive series of 128 patients who received a bone allograft was analyzed. The minimal follow-up was 18 months. Fracture, nonunion, infection and explantation were investigated using a multivariate analysis and logistical regression. Kaplan-Meier survival of the allograft was performed, using allograft removal as the end point. Tumour disease was excluded from this study. Patients were followed up for an average 103 months. Bone tumour occurred in 78% of the patients whereas revision arthroplasty was the cause of implantation in 15% of them. Nonunion was the most prevalent complication, occurring in 35% of the grafts. For nonunion occurrence, the type of reconstruction was found to be a significant variable, the intercalary allograft being the most exposed. Primary bone autografting at the anastomotic site was not significant to prevent nonunion. Fracture of the allograft was the second most frequent complication with a prevalence of 16.4%. The length of the allograft and an osteoarticular allograft were two significant variables in that occurrence. Infection of the allograft was present with a rate of 5.4% of patients. Explantation of failed allografts occurred in 30% of them. The duration of the frozen storage of the allograft and the donor age of the allograft were not significant on any local complication occurrence. Bone allografts are a reliable material but a high rate of local complications must be anticipated.

Improved accuracy with 3D planning and patient-specific instruments during simulated pelvic bone tumor surgery.

In orthopaedic surgery, resection of pelvic bone tumors can be inaccurate due to complex geometry, limited visibility and restricted working space of the pelvis. The present study investigated accuracy of patient-specific instrumentation (PSI) for bone-cutting during simulated tumor surgery within the pelvis. A synthetic pelvic bone model was imaged using a CT-scanner. The set of images was reconstructed in 3D and resection of a simulated periacetabular tumor was defined with four target planes (ischium, pubis, anterior ilium, and posterior ilium) with a 10-mm desired safe margin. Patient-specific instruments for bone-cutting were designed and manufactured using rapid-prototyping technology. Twenty-four surgeons (10 senior and 14 junior) were asked to perform tumor resection. After cutting, ISO1101 location and flatness parameters, achieved surgical margins and the time were measured. With PSI, the location accuracy of the cut planes with respect to the target planes averaged 1 and 1.2 mm in the anterior and posterior ilium, 2 mm in the pubis and 3.7 mm in the ischium (p < 0.0001). Results in terms of the location of the cut planes and the achieved surgical margins did not reveal any significant difference between senior and junior surgeons (p = 0.2214 and 0.8449, respectively). The maximum differences between the achieved margins and the 10-mm desired safe margin were found in the pubis (3.1 and 5.1 mm for senior and junior surgeons respectively). Of the 24 simulated resection, there was no intralesional tumor cutting. This study demonstrates that using PSI technology during simulated bone cuts of the pelvis can provide good cutting accuracy. Compared to a previous report on computer assistance for pelvic bone cutting, PSI technology clearly demonstrates an equivalent value-added for bone cutting accuracy than navigation technology. When in vivo validated, PSI technology may improve pelvic bone tumor surgery by providing clinically acceptable margins.

Computer-assisted planning and navigation improves cutting accuracy during simulated bone tumor surgery of the pelvis.

BACKGROUND: Resection of bone tumors within the pelvis requires good cutting accuracy to achieve satisfactory safe margins. Manually controlled bone cutting can result in serious errors, especially due to the complex three-dimensional geometry, limited visibility, and restricted working space of the pelvic bone. This experimental study investigated cutting accuracy during navigated and non-navigated simulated bone tumor cutting in the pelvis. METHODS: A periacetabular tumor resection was simulated using a pelvic bone model. Twenty-three operators (10 senior and 13 junior surgeons) were asked to perform the tumor cutting, initially according to a freehand procedure and later with the aid of a navigation system. Before cutting, each operator used preoperative planning software to define four target planes around the tumor with a 10-mm desired safe margin. After cutting, the location and flatness of the cut planes were measured, as well as the achieved surgical margins and the time required for each cutting procedure. RESULTS: The location of the cut planes with respect to the target planes was significantly improved by using the navigated cutting procedure, averaging 2.8 mm as compared to 11.2 mm for the freehand cutting procedure (p < 0.001). There was no intralesional tumor cutting when using the navigation system. The maximum difference between the achieved margins and the 10-mm desired safe margin was 6.5 mm with the navigated cutting process (compared to 13 mm with the freehand cutting process). CONCLUSIONS: Cutting accuracy during simulated bone cuts of the pelvis can be significantly improved by using a freehand process assisted by a navigation system. When fully validated with complementary in vivo studies, the planning and navigation-guided technologies that have been developed for the present study may improve bone cutting accuracy during pelvic tumor resection by providing clinically acceptable margins.

Measurement of bone cyst fluid volume using k-means clustering.

We designed a semiautomatic segmentation method to easily measure the volume of a bone cyst (simple or aneurysmal) from magnetic resonance imaging (MRI). This method only considers the fluid part of the cyst, even when there are several fluid intensities (fluid-fluid levels) or the cyst is multi-loculated. The nonhomogeneity phenomenon inherent in MRI was handled by a k-means clustering algorithm that classified all of the voxels corresponding to the cyst fluid as the same voxel intensity. Level-set segmentation was expanded into the whole cyst volume and the resulting segmented volume provided the measured cyst volume. The semiautomatic method was compared with the usual manual method (manual contour tracing) in terms of its ability to measure a known volume of water (gold standard) as well as the volume of 29 bone cysts. Both methods were equivalent with regards to the gold standard, but the semiautomatic method was more accurate. In terms of the experimental measurements, the semiautomatic method was more repeatable and reproducible, and less time-consuming and fastidious than the manual method. Our semiautomatic method uses only freeware and can be used routinely whenever measurement of a bone cyst volume is needed.

Accuracy in planar cutting of bones: an ISO-based evaluation.

BACKGROUND: Computer- and robot-assisted technologies are capable of improving the accuracy of planar cutting in orthopaedic surgery. This study is a first step toward formulating and validating a new evaluation methodology for planar bone cutting, based on the standards from the International Organization for Standardization. METHODS: Our experimental test bed consisted of a purely geometrical model of the cutting process around a simulated bone. Cuts were performed at three levels of surgical assistance: unassisted, computer-assisted and robot-assisted. We measured three parameters of the standard ISO1101:2004: flatness, parallelism and location of the cut plane. RESULTS: The location was the most relevant parameter for assessing cutting errors. The three levels of assistance were easily distinguished using the location parameter. CONCLUSIONS: Our ISO methodology employs the location to obtain all information about translational and rotational cutting errors. Location may be used on any osseous structure to compare the performance of existing assistance technologies.

Surgical inaccuracy of tumor resection and reconstruction within the pelvis: an experimental study.

BACKGROUND AND PURPOSE: Osseous pelvic tumors can be resected and reconstructed using massive bone allografts. Geometric accuracy of the conventional surgical procedure has not yet been documented. The aim of this experimental study was mainly to assess accuracy of tumoral resection with a 10-mm surgical margin, and also to evaluate the geometry of the host-graft reconstruction. METHODS: An experimental model on plastic pelvises was designed to simulate tumor resection and reconstruction. 4 experienced surgeons were asked to resect 3 different tumors and to reconstruct pelvises. 24 resections and host-graft junctions were available for evaluation. Resection margins were measured. Several methods were created to evaluate geometric properties of the host-graft junction. RESULTS: The probability of a surgeon obtaining a 10-mm surgical margin with a 5-mm tolerance above or below, was 52% (95% CI: 37-67). Maximal gap, gap volume, and mean gap between host and graft was 3.3 (SD 1.9) mm, 2.7 (SD 2.1) cm3 and 3.2 (SD 2.1) mm, respectively. Correlation between these 3 reconstruction measures and the degree of contact at the host-graft junction was poor. INTERPRETATION: 4 experienced surgeons did not manage to consistently respect a fixed surgical margin under ideal working conditions. The complex 3-dimensional architecture of the pelvis would mainly explain this inaccuracy. Solutions to this might be to increase the surgical margin or to use computer- and robotic-assisted technologies in pelvic tumor resection. Furthermore, our attempt to evaluate geometry of the pelvic reconstruction using simple parameters was not satisfactory. We believe that there is a need to define new standards of evaluation.