Receiver Operating Characteristic and Location Analysis of Simulated Near-Infrared Tomography Images

Receiver operating characteristic (ROC) analysis was performed on simulated near-infrared tomography images, using both human observer and contrast-to-noise ratio (CNR) computational assessment, for application in breast cancer imaging. In the analysis, a nonparametric approach was applied for estimating the ROC curves. Human observer detection of objects had superior capability to localize the presence of heterogeneities when the objects were small with high contrast, with a minimum detectable threshold of CNR near 3.0 to 3.3 in the images. Human observers were able to detect heterogeneities in the images below a size limit of 4 mm, yet could not accurately find the location of these objects when they were below 10 mm diameter. For large objects, the lower limit of a detectable contrast limit was near 10% increase relative to the background. The results also indicate that iterations of the nonlinear reconstruction algorithm beyond 4 did not significantly improve the human detection ability, and degraded the overall localization ability for the objects in the image, predominantly by increasing the noise in the background. Interobserver variance performance in detecting objects in these images was low, suggesting that because of the low spatial resolution, detection tasks with NIR tomography is likely consistent between human observers

Design of an Epidemiologic Study of Drinking Water Arsenic Exposure and Skin and Bladder Cancer Risk in a U.S. Population

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic

Surgical versus nonsurgical therapy for lumbar spinal stenosis.

BACKGROUND: Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. METHODS: Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. RESULTS: A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. CONCLUSIONS: In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].)

Diffusion of digital breast tomosynthesis among women in primary care: associations with insurance type

Abstract Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth ‐Brigham and Women's Hospital Population‐based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among women aged 40–89. A longitudinal repeated measures analysis estimated the proportion of DBT performed for screening or diagnostic indications over time and by insurance type. During the study period, 93,182 mammograms were performed on 48,234 women. Of these exams, 16,506 DBT tests were performed for screening (18.1%) and 2537 were performed for diagnosis (15.7%). Between 2011 and 2014, DBT utilization increased in all insurance groups. However, by the latest observed period, screening DBT was used more frequently under private insurance (43.4%) than Medicaid (36.2%), Medicare (37.8%), other (38.6%), or no insurance (32.9%; P < 0.0001). No sustained differences in use of DBT for diagnostic testing were seen by insurance type. DBT is increasingly used for breast cancer screening and diagnosis. Use of screening DBT may be associated with insurance type. Surveillance is required to ensure that disparities in breast cancer screening are minimized as DBT becomes more widely available

Characterization of Hemoglobin, Water, and NIR Scattering in Breast Tissue: Analysis of Intersubject Variability and Menstrual Cycle Changes

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 μM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p\u3c0.0001), but no other average near-infrared parameter changes were significant. While repeatable and systematic changes were observed in all parameters for individual subjects, large intersubject variations were present in all parameters. In a survey of thirty-nine normal subjects, the total hemoglobin varied from 9 to 45 μM, with a systematic correlation observed between total hemoglobin concentration and breast radiographic density. Scattering power and scattering amplitude were also correlated with radiographic density, but oxygen saturation and water fraction were not. Images of breast lesions indicate that total hemoglobin-based contrast can be up to 200% relative to the background in the same breast. Yet, since the background hemoglobin values vary considerably among breasts, the maximum hemoglobin concentrations observed in cancer tumors may vary considerably as well. In light of these observations, it may be important to use hemoglobin contrast values relative to the background for a given breast, rather than absolute hemoglobin contrast when trying to compare the features of breast lesions among subjects

The Impact of Epidural Steroid Injections on the Outcomes of Patients Treated for Lumbar Disc Herniation: A Subgroup Analysis of the SPORT Trial.

BACKGROUND: The Spine Patient Outcomes Research Trial (SPORT) is a prospective, multicenter study of operative versus nonoperative treatment of lumbar intervertebral disc herniation. It has been suggested that epidural steroid injections may help improve patient outcomes and lower the rate of crossover to surgical treatment. METHODS: One hundred and fifty-four patients included in the intervertebral disc herniation arm of the SPORT who had received an epidural steroid injection during the first three months of the study and no injection prior to the study (the ESI group) were compared with 453 patients who had not received an injection during the first three months of the study or prior to the study (the No-ESI group). RESULTS: There was a significant difference in the preference for surgery between groups (19% in the ESI group compared with 56% in the No-ESI group, p \u3c 0.001). There was no difference in primary or secondary outcome measures at four years between the groups. A higher percentage of patients changed from surgical to nonsurgical treatment in the ESI group (41% versus 12% in the No-ESI, p \u3c 0.001). CONCLUSIONS: Patients with lumbar disc herniation treated with epidural steroid injection had no improvement in short or long-term outcomes compared with patients who were not treated with epidural steroid injection. There was a higher prevalence of crossover to nonsurgical treatment among surgically assigned ESI-group patients, although this was confounded by the increased baseline desire to avoid surgery among patients in the ESI group. Given these data, we concluded that more studies are necessary to establish the value of epidural steroid injection for symptomatic lumbar intervertebral disc herniation. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence

Predictors of Long-Term Opioid Use Among Patients With Painful Lumbar Spine Conditions

Our objective was to assess predictors of self-reported opioid use among patients with back pain due to lumbar disc herniation or spinal stenosis. Data was from the Spine Patient Outcomes Research Trial (SPORT), a multi-site observational study and randomized trial. We examined characteristics shown or hypothesized to be associated with opioid use. Using generalized estimating equations, we modeled associations of each potential predictor with opioid use at 12 and 24 months. At baseline, 42% of participants reported opioid use. Of these participants, 25% reported continued use at 12 months and 21% reported use at 24 months. In adjusted models, smoking (RR=1.9, p<0.001 at 12 months; RR=1.5, p=0.043 at 24 months) and non-surgical treatment (RR=1.7, p<0.001 at 12 months; RR=1.8, p=0.003 at 24 months) predicted long-term opioid continuation. Among participants not using opioids at baseline, incident use was reported by 8% at 12 and 7% at 24 months. We found no significant predictors of incident use at 12 or 24 months in the main models. In conclusion, nonsurgical treatment and smoking independently predicted long-term continued opioid use. To our knowledge, this is the first longitudinal study to assess predictors of long-term and incident opioid use among patients with lumbar spine conditions

Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis.

BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials. METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, with higher scores indicating less severe symptoms) and the modified Oswestry Disability Index (100-point scale, with lower scores indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2 years. RESULTS: We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either treatment. CONCLUSIONS: In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials.gov number, NCT00000409 [ClinicalTrials.gov].)

Effect of head impacts on diffusivity measures in a cohort of collegiate contact sport athletes

Objective: To determine whether exposure to repetitive head impacts over a single season affects white matter diffusion measures in collegiate contact sport athletes. Methods: A prospective cohort study at a Division I NCAA athletic program of 80 nonconcussed varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration time history of the head following impact, and 79 non–contact sport athletes. Assessment occurred preseason and shortly after the season with diffusion tensor imaging and neurocognitive measures. Results: There was a significant (p 5 0.011) athlete-group difference for mean diffusivity (MD) in the corpus callosum. Postseason fractional anisotropy (FA) differed (p 5 0.001) in the amygdala (0.238 vs 0.233). Measures of head impact exposure correlated with white matter diffusivity measures in several brain regions, including the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory. Conclusion: This study suggests a relationship between head impact exposure, white matter diffusion measures, and cognition over the course of a single season, even in the absence of diagnosed concussion, in a cohort of college athletes. Further work is needed to assess whether such effects are short term or persisten