Cost-effectiveness analysis of screening for lung cancer with low dose spiral CT (computed tomography) in the Australian setting

Introduction:
Low dose spiral computed tomography (CT) is a sensitive screening tool for lung cancer that is currently being evaluated in both non-randomised studies and randomised controlled trials.
Methods:
We conducted a quantitative decision analysis using a Markov model to determine whether, in the Australian setting, offering spiral CT screening for lung cancer to high risk individuals would be cost-effective compared with current practice. This exploratory analysis was undertaken predominantly from the perspective of the government as third-party funder. In the base-case analysis, the costs and health outcomes (life-years saved and quality-adjusted life years) were calculated in a hypothetical cohort of 10,000 male current smokers for two alternatives: (1) screen for lung cancer with annual CT for 5 years starting at age 60 year and treat those diagnosed with cancer or (2) no screening and treat only those who present with symptomatic cancer.
Results:
For male smokers aged 60–64 years, with an annual incidence of lung cancer of 552 per 100,000, the incremental cost-effectiveness ratio was $57,325 per life-year saved and $105,090 per QALY saved. For females aged 60–64 years with the same annual incidence of lung cancer, the cost-effectiveness ratio was $51,001 per life-year saved and $88,583 per QALY saved. The model was used to examine the relationship between efficacy in terms of the expected reduction in lung cancer mortality at 7 years and cost-effectiveness. In the base-case analysis lung cancer mortality was reduced by 27% and all cause mortality by 2.1%. Changes in the estimated proportion of stage I cancers detected by screening had the greatest impact on the efficacy of the intervention and the cost-effectiveness. The results were also sensitive to assumptions about the test performance characteristics of CT scanning, the proportion of lung cancer cases overdiagnosed by screening, intervention rates for benign disease, the discount rate, the cost of CT, the quality of life in individuals with early stage screen-detected cancer and disutility associated with false positive diagnoses. Given current knowledge and practice, even under favourable assumptions, reductions in lung cancer mortality of less than 20% are unlikely to be cost-effective, using a value of $50,000 per life-year saved as the threshold to define a “cost-effective” intervention.
Conclusion:
The most feasible scenario under which CT screening for lung cancer could be cost-effective would be if very high-risk individuals are targeted and screening is either highly effective or CT screening costs fall substantially.

Peripheral quantitative computed tomography in children and adolescents : the 2007 ISCD pediatric official positions

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society
of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the
pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.

Radiation exposure and the justification of computed tomography scanning in an Australian hospital emergency department

In an emergency department (ED), computed tomography (CT) is particularly beneficial in the investigation of high-speed trauma patients. With the advent of multidetector CT (MDCT) scanners, it is becoming faster and easier to conduct scans. In recent years, this has become evident with an increasing number of CT requests. Patients who have multiple CT scans during their hospital stay can receive radiation doses that have an increased theoretical risk of induction of cancer. It is essential that the clinical justification for each CT scan be considered on an individual basis and that due consideration is given to the radiation risk and possible diagnostic benefit. The current lack of a central State or Commonwealth data repository for medical images is a contributing factor to excessive radiation dosage to the population. The principles of justification and radiation risks are discussed in this study.

Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children

Background/Aim: The study investigated the relationship between indices of adiposity measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) in pre-pubertal children.

Subjects and methods: DXA-derived per cent body fat (%BF) was measured in 284 boys and 288 girls, aged 7–10 years. Cross-sections of the forearm (n=427) and lower leg (n=560) were obtained by pQCT to measure total cross-sectional area of the limb (Total CSA), Muscle CSA, Fat CSA, %Fat CSA (Fat CSA/Total CSA×100) and muscle density.

Results: Peripheral QCT-derived %Fat CSA in the forearm and lower leg correlated strongly with DXA-derived %BF (r=0.83–0.89, p<0.01) in both boys and girls. However, forearm and lower leg %Fat CSA were higher than whole body %BF by 5% and 10%, respectively. A better prediction of whole-body %BF was achieved by including %Fat CSA, muscle density and height into a hierarchical regression model. Using sex-specific regression equations, 87.7% of the boys and 83.7% of the girls had a predicted %BF within 3% units of the %BF obtained by DXA.

Conclusion: In pre-pubertal children, pQCT measures of adiposity are strongly associated with whole-body per cent body fat. This reproducible method could be an alternative technique to estimate body composition in this population.

Automated detection of lung nodules in computed tomography images: a review

Lung nodules refer to a range of lung abnormalities the detection of which can facilitate early treatment for lung patients. Lung nodules can be detected by radiologists through examining lung images. Automated detection systems that locate nodules of various sizes within lung images can assist radiologists in their decision making. This paper presents a study of the existing methods on automated lung nodule detection. It introduces a generic structure for lung nodule detection that can be used to represent and describe the existing methods. The structure consists of a number of components including: acquisition, pre-processing, lung segmentation, nodule detection, and false positives reduction. The paper describes the algorithms used to realise each component in different systems. It also provides a comparison of the performance of the existing approaches.

Interobserver reliability of computed tomography to diagnose scaphoid waist fracture union

Purpose : To determine the interobserver agreement and diagnostic performance characteristics of computed tomography (CT) for determining union of scaphoid waist fractures.

Methods : A total of 59 orthopedic and trauma surgeons rated for union a set of 30 sagittal CT scans of 30 scaphoid waist fractures. Of these fractures, 20 were treated nonoperatively, were imaged between 6 and 10 weeks after injury, and were known to have eventually achieved union. Ten were operatively confirmed to be ununited. We rated each scan as united or ununited using a Web-based rating application. We assessed interobserver reliability using Siegel's multirater Kappa. We calculated diagnostic performance characteristics using Bayesian formulas.

Results : The interobserver agreement among 59 raters was substantial. The average sensitivity, specificity, and accuracy of diagnosing union of scaphoid waist fractures on sagittal CT scans were 78%, 96%, and 84%, respectively. Assuming a 90% prevalence of fracture union of the scaphoid, the positive predictive value of a diagnosis of union on sagittal CT scan was 0.99 and the negative predictive value was 0.41.

Conclusions : Our results suggest that CT scans are accurate and reliable for diagnosis of union but inadequate for ruling out nonunion of scaphoid waist fractures between 6 and 10 weeks after injury.

Interobserver reliability of coronoid fracture classification : two-dimensional versus three-dimensional computed tomography

Purpose : This study tests the hypothesis that 3-dimensional computed tomography (CT) reconstructions improve interobserver agreement on classification and treatment of coronoid fractures compared with 2-dimensional CT.

Methods : A total of 29 orthopedic surgeons evaluated 10 coronoid fractures on 2 occasions (first with radiographs and 2-dimensional CT and then with radiographs and 3-dimensional CT), separated by a minimum of 2 weeks. Surgeons classified fractures according to the classifications of Regan and Morrey and of O'Driscoll et al., identified specific characteristics, recommended the most appropriate treatment approach, and made treatment recommendations. The kappa multirater measure (κ) was calculated to estimate agreement between observers.

Results : Regardless of the imaging modality used, there was fair to moderate agreement for most of the observations. Three-dimensional CT improved interobserver agreement in Regan and Morrey's classsication (κ3-dimensional = 0.51 vs κ2-dimensional = 0.40; p < .001) and O'Driscoll et al.'s classifications (κ3-dimensional = 0.48 vs κ2-dimensional = 0.42; p = .009). There were trends toward better reliability for 3-dimensional reconstruction in recognition of coronoid tip fractures (κ3-dimensional = 0.19, κ2-dimensional = 0.03; p = .268), comminution (κ3-dimensional = 0.41 vs κ2-dimensional = 0.29; p = .133), and impacted fragments (κ3-dimensional = 0.39 vs κ2-dimensional = 0.27; p = .094), and in surgeons' opinions on the need for something other than screws or plate for surgical fixation (κ3-dimensional = 0.31 vs κ2-dimensional = 0.15; p = .138). Interobserver agreement on treatment approach was better with 2-dimensional CT (κ3-dimensional = 0.27, κ2-dimensional = 0.32; p = .015).

Conclusions : Three-dimensional CT reconstructions improve interobserver agreement with respect to fracture classification compared with 2-dimensional CT.

Prognostic value of fat mass and skeletal muscle mass determined by computed tomography in patients who underwent transcatheter aortic valve implantation

Body composition (fat mass [FM] and skeletal muscle mass [SMM]) predicts clinical outcomes. In particular, loss of SMM (sarcopenia) is associated with frailty and mortality. There are no data on the prevalence and impact of FM and SMM in patients undergoing transcatheter aortic valve implantation (TAVI). The objective of this study is to determine body composition from pre-TAVI computed tomography (CT) and evaluate its association with clinical outcomes in patients who underwent TAVI. A total of 460 patients (mean age 81 ± 8 years, men: 51%) were included. Pre-TAVI CTs of the aorto-ilio-femoral axis were analyzed for FM and SMM cross-sectional area at the level of the third lumbar vertebrae (L3). Regression equations correlating cross-sectional area at L3 to total body FM and SMM were used to determine prevalence of sarcopenia, obesity, and sarcopenic obesity in patients (64%, 65%, and 46%, respectively). Most TAVI procedures were performed through a transfemoral approach (59%) using a balloon-expandable valve (94%). The 30-day and mid-term (median 12 months [interquartile range 6 to 27]) mortality rates were 6.1% and 29.6%, respectively. FM had no association with clinical outcomes, but sarcopenia predicted cumulative mortality (hazard ratio 1.55, 95% confidence interval 1.02 to 2.36, p = 0.04). In conclusion, body composition analysis from pre-TAVI CT is feasible. Sarcopenia, obesity, and sarcopenic obesity are prevalent in the TAVI population, with sarcopenia predictive of cumulative mortality.

Progressive computed tomography (CT) appearances preceding malignant spinal cord compression (MSCC) in men with castration-resistant prostate cancer

AIM: To test the hypothesis that computed tomography (CT)-based signs might precede symptomatic malignant spinal cord compression (MSCC) in men with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: A database was used to identify suitable mCRPC patients. Staging CT images were retrospectively reviewed for signs preceding MSCC. Signs of malignant paravertebral fat infiltration and epidural soft-tissue disease were defined and assessed on serial CT in 34 patients with MSCC and 58 control patients. The presence and evolution of the features were summarized using descriptive statistics. RESULTS: In MSCC patients, CT performed a median of 28 days prior to the diagnostic magnetic resonance imaging (MRI) demonstrated significant epidural soft tissue in 28 (80%) patients. The median time to MSCC from a combination of overt malignant paravertebral and epidural disease was 2.7 (0-14.6) months. Conversely, these signs were uncommon in the control cohort. CONCLUSIONS: Significant malignant paravertebral and/or epidural disease at CT precede MSCC in up to 80% of mCRPC patients and should prompt closer patient follow-up and consideration of early MRI evaluation. These CT-based features require further prospective validation.

Optical coherence tomography : age estimation of Calliphora vicina pupae in vivo?

Necrophagous blowfly pupae are valuable contributors to the estimation of post-mortem interval, should an accurate age estimate be obtained. At present, this is reliant on a combination of rearing and destructive methods conducted on preserved samples, including morphological observation and gene expression analyses. This study demonstrates the use of optical coherence tomography (OCT) as a tool for in vivo morphological observation and pupal age estimation. Using a Michelson OCT microscope, alive and preserved four and ten-day old Calliphora vicina pupae were scanned in different orientations. Two and three-dimensional images were created. Morphological characteristics such as the brain, mouthparts and legs were identifiable in both living and preserved samples, with distinct differences noted between the two ages. Absorption of light by the puparium results in a vertical resolution of 1-2 mm, preventing observation of deeper tissues. The use of contrast agents or a longer wavelength laser would improve the images obtainable. At present, the data suggests OCT provides a primary view of external and internal morphology, which can be used to distinguish younger and older pupae for further analysis of age and PMI estimation.

Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men

Introduction: It remains uncertain whether long-term participation in regular weight-bearing exercise confers an advantage to bone structure and strength in old age. The aim of this study was to investigate the relationship between lifetime sport and leisure activity participation on bone material and structural properties at the axial and appendicular skeleton in older men (>50 years).

Methods: We used dual-energy X-ray absorptiometry (DXA) to assess hip, spine and ultradistal (UD) radius areal bone mineral density (aBMD) (n=161), quantitative ultrasound (QUS) to measure heel bone quality (n=161), and quantitative computed tomography (QCT) to assess volumetric BMD, bone geometry and strength at the spine (L₁–L₃) and mid-femur (n=111). Current (>50+ years) and past hours of sport and leisure activity participation during adolescence (13–18 years) and adulthood (19–50 years) were assessed by questionnaire. This information was used to calculate the total time (min) spent participating in sport and leisure activities and an osteogenic index (OI) score for each participant, which provides a measure of participation in weight-bearing activities.

Results: Regression analysis revealed that a greater lifetime (13–50+ years) and mid-adulthood (19–50 years) OI, but not total time (min), was associated with a greater mid-femur total and cortical area, cortical bone mineral content (BMC), and the polar moment of inertia (I _p) and heel VOS (p ranging from <0.05 to <0.01). These results were independent of age, height (or femoral length) and weight (or muscle cross-sectional area). Adolescent OI scores were not found to be significant predictors of bone structure or strength. Furthermore, no significant relationships were detected with areal or volumetric BMD at any site. Subjects were then categorized into either a high (H) or low/non-impact (L) group during adolescence (13–18 years) and adulthood (19–50+ years) according to their OI scores during each of these periods. Three groups were subsequently formed to reflect weight-bearing impact categories during adolescence and then adulthood: LL, HL and HH. Compared to the LL group, mid-femur total and cortical area, cortical BMC and I _p were 6.5–14.2% higher in the HH group. No differences were detected between the LL and HL groups.

Conclusions: In conclusion, these findings indicate that long-term regular participation in sport and leisure activities categorized according to an osteogenic index [but not the total time (min) spent participating in all sport and leisure activities] was an important determinant of bone size, quality and strength, but not BMD, at loaded sites in older men. Furthermore, continued participation in weight-bearing exercise in early to mid-adulthood appears to be important for reducing the risk of low bone strength in old age.

Sequential 123-I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18-F-FDG-PET imaging)

Purpose Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with ¹²³I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci.
Methods We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation.
Results The 6-h IDEX scan (92%; κappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%;κappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; κappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy.
Conclusion The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.

Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention

Context The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear.

Objective To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography.

Design and Setting Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong.

Participants Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention.

Intervention Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent.

Main Outcome Measures Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level.

Results Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P = .03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 µmol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 µmol/L]; 95% CI, 1.27-1.49 mg/dL; P = .006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001).The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P = .15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events.

Conclusion Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.