Geographic Examination of COVID-19 Test Percent Positivity and Proportional Change in Cancer Screening Volume, National Breast and Cervical Cancer Early Detection Program.

INTRODUCTION: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume. METHODS: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS. RESULTS: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume. CONCLUSION: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

Variations in Screening Quality in a Federal Colorectal Cancer Screening Program for the Uninsured.

INTRODUCTION: Screening can decrease colorectal cancer incidence and mortality and is recommended in clinical practice guidelines. Poor quality of colorectal cancer screening can negate the benefit of screening. The objective of this study was to assess the quality of screening services provided by the Centers for Disease Control and Prevention's Colorectal Cancer Control Program from July 2009 through June 2015. METHODS: We collected data from the program's 29 grantees, funded to provide colorectal cancer screening and diagnostic services to asymptomatic, low-income, and underinsured or uninsured adults aged 50 to 64. We collected data on the dates and results of all screening and diagnostic tests and, for colonoscopies, on whether the cecum was reached, whether bowel preparation was adequate, and endoscopists' recommendations for the next test. RESULTS: Overall, 82.9% (range among grantees, 50.0%-97.2%) of positive FOBTs/FITs were followed up by colonoscopy; 95.2% of colonoscopies occurred within 180 days of the positive stool test. Cecal intubation rates ranged among grantees from 94.2% to 100%. Adenoma detection rates met recommended threshold levels for almost all grantees. Recommendations for rescreening and surveillance intervals deviated from guidelines in both directions. Of clients with normal colonoscopies, 85.3% (range, 37.7%-99.7%) were told to return in 10 years, as recommended in national guidelines. Of clients with advanced adenomas, 55.2% (range, 20.0%-84.6%) were told to return in 3 years as recommended, 25.4% (range, 3.8%-56.6%) in 5 or more years, and 18.6% (range, 0%-47.2%) in less than 3 years. CONCLUSION: Although overall screening quality was good, it varied considerably. Ongoing monitoring to identify performance problems is essential for all colorectal cancer screening activities, so that efforts designed to improve performance can be targeted to individual clinicians.

Clinical outcomes of mammography in the National Breast and Cervical Cancer Early Detection Program, 2009-2012.

PURPOSE: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) enrolls asymptomatic women for cancer screening and symptomatic women for diagnostic services. This study describes the results of mammograms provided by the NBCCEDP, by examination indication (screening or diagnostic), and by age group. METHODS: For the first NBCCEDP-funded mammogram received during 2009-2012, we calculated age-specific percentages of abnormal findings, rates of follow-up testing, and invasive and in situ breast cancer diagnoses per 1,000 mammograms. Logistic regression was used to estimate the odds for each of these outcomes by examination indication. RESULTS: The NBCCEDP provided 941,649 screening, 175,310 diagnostic, and 30,434 unknown indication mammograms to 1,147,393 women. The percentage with abnormal mammograms was higher for diagnostic mammograms (40.1 %) than for screening mammograms (15.5 %). Compared with women aged 40-49 years, fewer women aged 50-64 years had abnormal results for screening (13.7 vs. 19.7 %) and diagnostic mammograms (37.7 vs. 42.7 %). Follow-up rates per 1,000 mammograms were lower among women aged 50-64 compared to those aged 40-49 (screening: 143.9 vs. 207.5; diagnostic: 645.3 vs. 760.9); biopsy rates exhibited a similar pattern (screening: 24.1 vs. 32.9; diagnostic: 167.7 vs. 169.7). For screening mammograms, older women had more cancers detected than younger women (invasive: 3.6 vs. 2.2; in situ: 2.3 vs. 2.0). Similarly, for diagnostic mammograms, cancer detection was higher for older women (invasive: 67.8 vs. 36.6; in situ: 17.4 vs. 11.1). CONCLUSIONS: Abnormal mammograms and diagnostic follow-up procedures were less frequent in women aged 50-64 years compared to women aged 40-49 years, while breast cancer detection was higher, regardless of indication for the mammogram. Some of these differences between age groups were greater for screening mammograms than for diagnostic mammograms. Cancer detection rates were higher for diagnostic mammograms compared with screening mammograms. These findings support the NBCCEDP's priority of serving women aged 50-64 years and providing both screening and diagnostic mammograms.

Clinical outcomes from the CDC's Colorectal Cancer Screening Demonstration Program.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer-related deaths among US men and women. Screening rates have been slow to increase, and disparities in screening remain. METHODS: To address the disparity in screening for this high burden but largely preventable disease, the Centers for Disease Control and Prevention (CDC) designed and established a 4-year Colorectal Cancer Screening Demonstration Program (CRCSDP) in 2005 for low-income, under-insured or uninsured men and women aged 50 to 64 years in 5 participating US program sites. In this report, the authors describe the design of the CRCSDP and the overall clinical findings and screening test performance characteristics, including the positive fecal occult blood testing (FOBT) rate; the rates of polyp, adenoma, and cancer detection with FOBTs and colonoscopies; and the positive predicative value for polyps, adenomas, and cancers. RESULTS: In total, 5233 individuals at average risk and increased risk were screened for colorectal cancer across all 5 sites, including 44% who underwent screening FOBT and 56% who underwent screening colonoscopy. Overall, 77% of all individuals screened were women. The FOBT positivity rate was 10%. Results from all screening or diagnostic colonoscopies indicated that 75% had negative results and required a repeat screening colonoscopy in 10 years, 16% had low-risk adenomas and required surveillance colonoscopy in 5 to 10 years, 8% had high-risk adenomas and required surveillance colonoscopy in 3 years, and 0.6% had invasive cancers. CONCLUSIONS: This report documents the successes and challenges in implementing the CDC's CRCSDP and describes the clinical outcomes of this 4-year initiative, the patterns in program uptake and test choice, and the comparative test performance characteristics of FOBT versus colonoscopy. Patterns in final outcomes from the follow-up of positive screening tests were consistent with national registry data.

Pathophysiology of primary spinal syringomyelia.

OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. RESULTS: In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. CONCLUSIONS: These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245.

Timeliness of cervical cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program.

OBJECTIVES: To examine time intervals from cervical cancer screening to diagnosis and treatment initiation among low-income and uninsured women in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) during two consecutive time periods. METHODS: We analyzed NBCCEDP data for women with abnormal Pap tests (n=100,167), from which 1,417 invasive cervical cancers were diagnosed. We examined two time intervals for this study: diagnostic interval (time from abnormal Pap test to the date of definitive diagnosis) and treatment initiation interval (time from definitive diagnosis to treatment initiation) for two time periods: 1996-2002 and 2003-2009. We compared median time intervals for diagnostic and treatment initiation using the Kruskal-Wallis test. Adjusted proportions (predicted marginals) were calculated using logistic regression to examine diagnosis and treatment within program benchmarks (≤60 days). RESULTS: Median diagnostic intervals decreased overall by 6 days (54 vs. 48 days, p<0.001). This decrease in the median diagnostic interval was noted for all variables examined. The median treatment initiation intervals remained stable over the two time periods. CONCLUSIONS: Women screened by the NBCCEDP receive diagnostic follow-up and initiate treatment within preestablished program guidelines.

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

CONTEXT: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. OBJECTIVE: To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. DESIGN: A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. SETTING: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). INTERVENTIONS: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. MAIN OUTCOME MEASURES: Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. RESULTS: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. CONCLUSION: In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.

Timeliness of breast cancer diagnosis and initiation of treatment in the National Breast and Cervical Cancer Early Detection Program, 1996-2005.

OBJECTIVES: To determine the effects of program policy changes, we examined service delivery benchmarks for breast cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: We analyzed NBCCEDP data for women with abnormal mammogram or clinical breast examination (n=382 416) from which 23 701 cancers were diagnosed. We examined time to diagnosis and treatment for 2 time periods: 1996 to 2000 and 2001 to 2005. We compared median time for diagnostic, treatment initiation, and total intervals with the Kruskal-Wallis test. We calculated adjusted proportions (predicted marginals) with logistic regression to examine diagnosis and treatment within program benchmarks (

A combined approach to women's health is associated with a greater likelihood of repeat mammography in a population of financially disadvantaged women.

INTRODUCTION: Integrating one or more public health programs may improve the ability of programs to achieve common goals. Expanding knowledge on how program integration occurs, how it benefits each individual program, and how it contributes to the achievement of common goals is an important area of inquiry in public health. METHODS: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program combined data from 10 of their overlapping state or tribal programs to calculate prevalence estimates of repeat mammography at 18 months. The data were stratified by whether women attended the combined program or only the NBCCEDP. Logistic regression analyses were conducted to identify factors that were thought to independently contribute to a greater likelihood of a woman receiving a repeat mammogram. RESULTS: Women who participated in both programs were 1.5 to 5.1 times as likely to be rescreened, depending on program location, as women who participated only in the NBCCEDP. WISEWOMAN participants who received a follow-up WISEWOMAN screening for chronic disease risk factors within a year of their initial WISEWOMAN screening were 5 times more likely to return for a follow-up mammogram through the NBCCEDP than were WISEWOMAN participants who did not. DISCUSSION: Participation in both the NBCCEDP and the WISEWOMAN program is associated with a greater likelihood of a woman returning for a follow-up mammogram within 18 months of her initial examination. Collecting more in-depth information on motivational factors and on the association between receipt of multiple services and a woman's engagement in a health program should be the subject of future research.

MRI-guided HDR prostate brachytherapy in standard 1.5T scanner.

PURPOSE: Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard "closed-bore" 1.5T scanner. METHODS AND MATERIALS: Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T(2)-weighted MRI. RESULTS: Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V(100)) achieved was 94% (mean, 92%; 95% confidence interval, 89-95%). The urethral V(125) ranged from 0% to 18% (median, 5%), and the rectal V(75) ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients. CONCLUSION: High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.

Intraoperative infrared functional imaging of human brain.

We hypothesized that it would be possible to detect the distribution of cortical activation by using a sensitive, rapid, high-resolution infrared imaging technique to monitor changes in local cerebral blood flow induced by changes in focal cortical metabolism. In a prospective study, we recorded in 21 patients the emission of infrared radiation from the exposed human cerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02 degrees C). The language and sensorimotor cortex was identified by standard mapping methods (cortical stimulation, median nerve somatosensory-evoked potential, functional magnetic resonance imaging), which were compared with infrared functional localization. The temperature gradients measured during surgery are dominated by changes in local cerebral blood flow associated with evoked functional activation. The distribution of the evoked temperature changes overlaps with, but extends beyond, functional regions identified by standard mapping techniques. The distribution observed via infrared mapping is consistent with distributed and complex functional representation of the cerebral cortex, rather than the traditional concept of discrete functional loci demonstrated by brief cortical stimulation during surgery and by noninvasive functional imaging techniques. By providing information on the spatial and temporal patterns of sensory-motor and language representation, infrared imaging may prove to be a useful approach to study brain function.