Bone Marrow Biopsies: Is CT, Fluoroscopy, or no Imaging Guidance the Most Cost-Effective Strategy?

RATIONALE AND OBJECTIVES: To determine the most cost-effective strategy for pelvic bone marrow biopsies. MATERIALS AND METHODS: A decision analytic model from the health care system perspective for patients with high clinical concern for multiple myeloma (MM) was used to evaluate the incremental cost-effectiveness of three bone marrow core biopsy techniques: computed tomography (CT) guided, and fluoroscopy guided, no-imaging (landmark-based). Model input data on utilities, costs, and probabilities were obtained from comprehensive literature review and expert opinion. Costs were estimated in 2023 U.S. dollars. Primary effectiveness outcome was quality adjusted life years (QALY). Willingness to pay threshold was $100,000 per QALY gained. RESULTS: No-imaging based biopsy was the most cost-effective strategy as it had the highest net monetary benefit ($4218) and lowest overall cost ($92.17). Fluoroscopy guided was excluded secondary to extended dominance. CT guided biopsies were less preferred as it had an incremental cost-effectiveness ratio ($334,043) greater than the willingness to pay threshold. Probabilistic sensitivity analysis found non-imaging based biopsy to be the most cost-effective in 100% of simulations and at all willingness to pay thresholds up to $200,000. CONCLUSION: No-imaging based biopsy appears to be the most cost-effective strategy for bone marrow core biopsy in patients suspected of MM. CLINICAL RELEVANCE: No imaging guidance is the preferred strategy, although image-guidance may be required for challenging anatomy. CT image interpretation may be helpful for planning biopsies. Establishing a non-imaging guided biopsy service with greater patient anxiety and pain support may be warranted.

Cost-effectiveness analysis of KTE-X19 CAR T therapy versus real-world standard of care in patients with relapsed/refractory mantle cell lymphoma post BTKi in England.

AIMS: The objective of this study is to estimate the cost-effectiveness of KTE-X19 versus standard of care (SoC) in the treatment of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) post-Bruton tyrosine kinase inhibitor (BTKi) treatment from a UK healthcare perspective. MATERIALS AND METHODS: A three-state partitioned survival model (pre-progression, post-progression and death) with a cycle length of one month was used to extrapolate progression-free and overall survival over a lifetime horizon. Population inputs along with KTE-X19 (brexucabtagene autoleucel) efficacy and safety data were derived from the single-arm trial ZUMA-2 (NCT02601313). The composition of SoC was informed by a literature-based meta-analysis, SoC efficacy data were obtained from the SCHOLAR-2 real-world study. Survival was modelled using standard parametric curves for SoC and a mixture-cure methodology for KTE-X19. It was assumed that patients whose disease had not progressed after five years experienced long-term remission. Costs, resource use and utility, and adverse event disutility inputs were obtained from published literature and publicly available data sources. An annual discount rate of 3.5% was applied to costs and health outcomes. Modelled outcomes for KTE-X19 and SoC included expected life years (LY), quality-adjusted life years (QALY) and total costs. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. RESULTS: Estimated median survival was 5.96 years for KTE-X19 and 1.38 for SoC. Discounted LYs, QALYs and lifetime costs were 8.27, 5.99 and £385,765 for KTE-X19 versus 1.98, 1.48 and £79,742 for SoC, respectively. The KTE-X19 versus SoC cost per QALY was £67,713 and the cost per LY was £48,645. Influential scenario analyses use alternative KTE-X19 survival curves and discount rates, and shorter time horizons. CONCLUSION: Considering the survival and quality of life benefits compared to SoC, KTE-X19 for R/R MCL appears as a cost-effective treatment in the real-world UK setting.

Electrical impedance myography for assessment of Duchenne muscular dystrophy.

OBJECTIVE: Sensitive, objective, and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance myography (EIM) could serve this purpose. METHODS: In this nonblinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model. RESULTS: In boys > 7.0 years old, a significant difference in the slope of EIM phase ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p = 0.023, 95% confidence interval (CI) = -0.013, -0.14; at 2 years, this difference was -0.048/month, p < 0.0001, 95% CI = -0.028, -0.068. In boys ≤ 7.0 years old, differences appeared at 6 months in gastrocnemius (EIM phase slope = -0.83 °/kHz/mo, p = 0.007, 95% CI = -0.26, -1.40). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase ratio (0.057/mo, p = 0.00019, 95% CI = 0.028, 0.086) and EIM phase slope (0.14 °/kHz/mo, p = 0.013, 95% CI = 0.028, 0.25), consistent with corticosteroids' known clinical benefit. INTERPRETATION: EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Because EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials. Ann Neurol 2017;81:622-632.

Quantitative Ultrasound Assessment of Duchenne Muscular Dystrophy Using Edge Detection Analysis.

OBJECTIVES: The purpose of this study was to investigate the ability of quantitative ultrasound (US) using edge detection analysis to assess patients with Duchenne muscular dystrophy (DMD). METHODS: After Institutional Review Board approval, US examinations with fixed technical parameters were performed unilaterally in 6 muscles (biceps, deltoid, wrist flexors, quadriceps, medial gastrocnemius, and tibialis anterior) in 19 boys with DMD and 21 age-matched control participants. The muscles of interest were outlined by a tracing tool, and the upper third of the muscle was used for analysis. Edge detection values for each muscle were quantified by the Canny edge detection algorithm and then normalized to the number of edge pixels in the muscle region. The edge detection values were extracted at multiple sensitivity thresholds (0.01-0.99) to determine the optimal threshold for distinguishing DMD from normal. Area under the receiver operating curve values were generated for each muscle and averaged across the 6 muscles. RESULTS: The average age in the DMD group was 8.8 years (range, 3.0-14.3 years), and the average age in the control group was 8.7 years (range, 3.4-13.5 years). For edge detection, a Canny threshold of 0.05 provided the best discrimination between DMD and normal (area under the curve, 0.96; 95% confidence interval, 0.84-1.00). According to a Mann-Whitney test, edge detection values were significantly different between DMD and controls (P < .0001). CONCLUSIONS: Quantitative US imaging using edge detection can distinguish patients with DMD from healthy controls at low Canny thresholds, at which discrimination of small structures is best. Edge detection by itself or in combination with other tests can potentially serve as a useful biomarker of disease progression and effectiveness of therapy in muscle disorders.

MRI assessment of regional differences in phosphorus-31 metabolism and morphological abnormalities of the foot muscles in diabetes.

PURPOSE: To assess differences in the phosphorus-31 (31 P) metabolism and morphology in multiple muscle regions in the forefoot of diabetic patients and normal subjects. MATERIALS AND METHODS: Fifteen diabetic patients and 15 normal subjects were assessed for muscle atrophy by 1 H magnetic resonance imaging (MRI) at 3T to grade the flexor hallucis, adductor hallucis, interosseous regions, and entire foot cross-section. Each region and the entire foot were also quantitatively evaluated for metabolic function using 31 P imaging for spatial mapping of the inorganic phosphate (Pi) to phosphocreatine (PCr) ratio (Pi/PCr). The ratio of viable muscle area to the predefined region areas (31 P/1 H) was calculated. The variability of each method was assessed by its coefficient of variation (CV). RESULTS: Muscle atrophy was significantly more severe in diabetic compared to normal subjects in all regions (P < 0.01). The 31 P/1 H area ratio was significantly larger in the adductor hallucis than in the other two regions (P < 0.05). The Pi/PCr ratio was significantly different between the two groups in the flexor hallucis and interosseous regions (P < 0.05) but not adductor hallucis region. The CV for Pi/PCr ranged from 10.13 to 55.84, while it ranged from 73.40 to 263.90 for qualitative grading. CONCLUSION: Changes in atrophy and metabolism appear to occur unequally between different regions of the forefoot in diabetes. The adductor hallucis region appears more capable of maintaining structural and metabolic integrity than the flexor hallucis or interosseous regions. The CV analysis suggests that the quantitative 31 P methods have less variability than the qualitative grading. J. Magn. Reson. Imaging 2016;44:1132-1142.

Assessment of aged mdx mice by electrical impedance myography and magnetic resonance imaging.

INTRODUCTION: Similar to magnetic resonance imaging (MRI), electrical impedance myography (EIM) is dependent on the presence and location of water in muscle to assess neuromuscular diseases. We compared the 2 technologies in mdx mice to better understand their relationship. METHODS: EIM and MRI, using T2 relaxation and diffusion-weighted imaging (DWI), were performed on the gastrocnemius of 10 mdx and 10 wild-type mice. Muscle function and tissue composition measurements were compared with the EIM and MRI data. RESULTS: EIM reactance and T2 relaxation mapping can discriminate healthy from diseased mice (P < .001 for both), but DWI could not. Both T2 relaxation and EIM reactance also correlated closely with muscle function/composition and with each other. CONCLUSION: Given the low cost of EIM and the simplicity of application, it may be a valuable alternative to muscle MRI in Duchenne muscular dystrophy, where simple cumulative indices of muscle health are being sought.

Cross-sectional evaluation of electrical impedance myography and quantitative ultrasound for the assessment of Duchenne muscular dystrophy in a clinical trial setting.

BACKGROUND: Electrical impedance myography and quantitative ultrasound are two noninvasive, painless, and effort-independent approaches for assessing neuromuscular disease. Both techniques have potential to serve as useful biomarkers in clinical trials in Duchenne muscular dystrophy. However, their comparative sensitivity to disease status and how they relate to one another are unknown. METHODS: We performed a cross-sectional analysis of electrical impedance myography and quantitative ultrasound in 24 healthy boys and 24 with Duchenne muscular dystrophy, aged 2 to 14 years with trained research assistants performing all measurements. Three upper and three lower extremity muscles were studied unilaterally in each child, and the data averaged for each individual. RESULTS: Both electrical impedance myography and quantitative ultrasound differentiated healthy boys from those with Duchenne muscular dystrophy (P < 0.001 for both). Quantitative ultrasound values correlated with age in Duchenne muscular dystrophy boys (rho = 0.45; P = 0.029), whereas electrical impedance myography did not (rho = -0.31; P = 0.14). However, electrical impedance myography phase correlated with age in healthy boys (rho = 0.51; P = 0.012), whereas quantitative ultrasound did not (rho = -0.021; P = 0.92). In Duchenne muscular dystrophy boys, electrical impedance myography phase correlated with the North Star Ambulatory Assessment (rho = 0.65; P = 0.022); quantitative ultrasound revealed a near-significant association (rho = -0.56; P = 0.060). The two technologies trended toward a moderate correlation with one another in the Duchenne muscular dystrophy cohort but not in the healthy group (rho = -0.40; P = 0.054 and rho = -0.32; P = 0.13, respectively). CONCLUSIONS: Electrical impedance myography and quantitative ultrasound are complementary modalities for the assessment of boys with Duchenne muscular dystrophy; further study and application of these two modalities alone or in combination in a longitudinal fashion are warranted.

A needs assessment of musculoskeletal fellowship training: a survey of practicing musculoskeletal radiologists.

OBJECTIVE: The purpose of this study was to conduct a needs assessment of musculo-skeletal radiologists regarding their musculoskeletal training experience and attitude toward a standardized musculoskeletal fellowship curriculum. MATERIALS AND METHODS: An anonymous survey was sent to the Society of Skeletal Radiology membership querying musculoskeletal radiologists' practice patterns, fellowship program, curriculum, and modes of learning. RESULTS: Of 216 respondents (26% response rate), 87% were musculoskeletal fellowship trained. The majority performed MRI, CT, and radiography (99%); arthrography (95%); spine MRI (77%); pediatric musculoskeletal imaging (75%); musculoskeletal ultrasound (63%); and biopsies (62%). During fellowship, 72% read spine MRI; 74% pediatric musculo-skeletal imaging, and 49% musculoskeletal ultrasound (49%); 33% received no spine procedural training. Most felt comfortable performing arthrography, joint injections, and bone and soft-tissue biopsies but not spine biopsies. Of the total, 33% received a curriculum and 67% had no formal feedback and 56% did not evaluate their program. The highest rated program features were teaching by attending physicians (69%), case variety (54%), and procedural training (49%). The lowest rated features were lack of curriculum (57%), lack of structured learning (48%), and lack of mentoring (24%). The favorite mode of learning was one-on-one readout with attending physicians (90%), and 85% agreed that a standardized musculoskeletal fellowship curriculum would benefit musculoskeletal training. CONCLUSION: Although musculoskeletal radiologists believe they were adequately trained for practice, there are perceived deficiencies in spine MRI, pediatric musculoskeletal imaging, and musculoskeletal ultrasound. A standardized musculoskeletal fellowship curriculum would provide improved structure and a defined educational program. Clear expectations, performance assessment, feedback, and programmatic evaluation should be core elements of the training of every musculoskeletal fellow.

Recent patents on nucleoside and nucleotide inhibitors for HCV.

Hepatitis C virus (HCV) infection is a leading cause of liver diseases such as cirrhosis and hepatocellular carcinoma. There are estimated 170 million people worldwide chronically infected with the virus. The lack of highly effective and safe therapeutics for HCV infection has spurred intensive efforts to develop anti-HCV drugs as evidenced by the large number of new patent applications filed each year. Nucleoside and nucleotide inhibitors are the analogues of DNA or RNA substrates, and they inhibit viral polymerases by acting as chain terminators, viral mutagens, or simple competitive inhibitors. The successful development of various nucleoside and nucleotide inhibitors for the treatment of HIV and HBV infections has prompted the drug industry to seek similar strategies for HCV. This review summarizes recently issued or published patents covering nucleoside and nucleotide inhibitors for HCV. The claimed chemical structures and available biological activities, mechanism of action, and drug resistance profiles are discussed. The development status of several promising nucleoside inhibitors is also described.