Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-30 (of 34 Records) |
Query Trace: Soman A[original query] |
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Variation in cervical cancer screening test utilization and results in a United States-based program
Dorismond VG , Saraiya M , Gopalani SV , Soman A , Kenney K , Miller J , Sawaya GF . Gynecol Oncol 2024 184 96-102 BACKGROUND: Little is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States. METHODS: Data from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21-65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories. RESULTS: Primary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30-65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9-72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7-28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4-19.1%) to 49.0% (95% CI 48.4-49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results. CONCLUSIONS: Cervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region. |
Breast, cervical, and colorectal cancer screening test use in the US territories of Guam, Puerto Rico, and the US Virgin Islands
Gopalani SV , Soman A , Shapiro JA , Miller JW , Ortiz-Ortiz KJ , Castañeda-Avila MA , Buenconsejo-Lum LE , Fredericks LE , Tortolero-Luna G , Saraiya M . Cancer Epidemiol 2023 84 102371 BACKGROUND: The United States Preventive Services Task Force (USPSTF) recommends breast, cervical, and colorectal cancer screening among eligible adults, but information on screening use in the US territories is limited. METHODS: To estimate the proportion of adults up-to-date with breast, cervical, and colorectal cancer screening based on USPSTF recommendations, we analyzed Behavioral Risk Factor Surveillance System data from 2016, 2018, and 2020 for the 50 US states and DC (US) and US territories of Guam and Puerto Rico and from 2016 for the US Virgin Islands. Age-standardized weighted proportions for up-to-date cancer screening were examined overall and by select characteristics for each jurisdiction. RESULTS: Overall, 67.2% (95% CI: 60.6-73.3) of women aged 50-74 years in the US Virgin Islands, 74.8% (70.9-78.3) in Guam, 83.4% (81.7-84.9) in Puerto Rico, and 78.3% (77.9-78.6) in the US were up-to-date with breast cancer screening. For cervical cancer screening, 71.1% (67.6-74.3) of women aged 21-65 years in Guam, 81.3% (74.6-86.5) in the US Virgin Islands, 83.0% (81.7-84.3) in Puerto Rico, and 84.5% (84.3-84.8) in the US were up-to-date. For colorectal cancer screening, 45.2% (40.0-50.5) of adults aged 50-75 years in the US Virgin Islands, 47.3% (43.6-51.0) in Guam, 61.2% (59.5-62.8) in Puerto Rico, and 69.0% (68.7-69.3) in the US were up-to-date. Adults without health care coverage reported low test use for all three cancers in all jurisdictions. In most jurisdictions, test use was lower among adults with less than a high school degree and an annual household income of < $25,000. CONCLUSION: Cancer screening test use varied between the US territories, highlighting the importance of understanding and addressing territory-specific barriers. Test use was lower among groups without health care coverage and with lower income and education levels, suggesting the need for targeted evidence-based interventions. |
Accelerating cervical cancer screening with human papillomavirus genotyping
Sawaya GF , Saraiya M , Soman A , Gopalani SV , Kenney K , Miller J . Am J Prev Med 2023 64 (4) 552-555 INTRODUCTION: Selective utilization of human papillomavirus (HPV) genotyping in cervical cancer screening can accelerate clinical management, leading to earlier identification and treatment of precancerous lesions and cancer. Specifically, immediate colposcopy (instead of 1-year return) is recommended in persons with normal cytology and HPV genotypes 16 and/or 18, and expedited treatment (instead of colposcopy) is recommended in persons with high-grade squamous intraepithelial lesion (HSIL) cytology and HPV genotype 16. The effects of implementing HPV testing and genotyping into a screening program are largely unknown. METHODS: Average-risk persons aged 30-65 years screened for cervical cancer in the National Breast and Cervical Cancer Early Detection Program from 2019 to 2020 were included (N=104,991). Percentage HPV genotyping test positivity was estimated within cytology result categories. Analyses were performed in 2022. RESULTS: The most common abnormality was positive high-risk HPV testing with normal cytology, representing 40.1% (7,155/17,832) of all abnormal test result categories; HSIL cytology represented 3.0% (530/17,832) of all abnormal test result categories. In high-risk HPV‒positive persons with normal or high-grade cytology, HPV genotyping could accelerate management (immediate colposcopy and expedited treatment) in 5.4% of all persons with abnormal screening test results; if HPV genotyping had been performed in all high-risk HPV‒positive persons with normal or HSIL cytology, approximately 13.1% could have accelerated management. CONCLUSIONS: HPV genotyping in human papillomavirus‒positive persons with normal or HSIL cytology could accelerate management in a sizable percentage of persons with abnormal test results and may be particularly useful in populations with challenges adhering to longitudinal follow-up. |
Risk of clear-cell adenocarcinoma of the vagina and cervix among US women with potential exposure to diethylstilbestrol in utero
White MC , Weir HK , Soman AV , Peipins LA , Thompson TD . Cancer Causes Control 2022 33 (8) 1121-1124 PURPOSE: Women exposed to diethylstilbestrol (DES) in utero were at elevated risk of clear-cell adenocarcinoma of the vagina and cervix (CCA) as young women. Previous research suggested that this elevated risk of CCA may persist into adulthood. We extended a published analysis to measure CCA risk as these women aged. METHODS: Standardized incidence ratios (SIR) compared CCA risk among women born from 1947 through 1971 (the DES-era) to CCA risk among the comparison group of women born prior to 1947, using registry data that covered the US population. RESULTS: Incidence rates of CCA among both cohorts increased with age. Among the DES-era birth cohort, higher rates of CCA were observed across all age groups except 55-59 years. SIR estimates had wide confidence intervals that often included the null value. CONCLUSIONS: Results are consistent with prior research and suggest an elevated risk of CCA in midlife and at older ages among women exposed in utero to DES. These results highlight unresolved issues regarding cancer risk among aging DES daughters and appropriate screening guidance. The examination of population-based cancer surveillance data may be a useful tool for monitoring trends in the incidence of other rare cancers over time among specific birth cohorts. |
Screening for colorectal cancer in the United States: correlates and time trends by type of test
Shapiro JA , Soman AV , Berkowitz Z , Fedewa SA , Sabatino SA , de Moor JS , Clarke TC , Doria-Rose VP , Breslau ES , Jamal A , Nadel MR . Cancer Epidemiol Biomarkers Prev 2021 30 (8) 1554-1565 BACKGROUND: It is strongly recommended that adults aged 50-75 years be screened for colorectal cancer (CRC). Recommended screening options include colonoscopy, sigmoidoscopy, computed tomography colonography, guaiac fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), or the more recently introduced FIT-DNA (FIT in combination with a stool DNA test). CRC screening programs can benefit from knowledge of patterns of use by test type and within population subgroups. METHODS: Using 2018 National Health Interview Survey data, we examined CRC screening test use for adults aged 50-75 years (N=10,595). We also examined time trends in CRC screening test use from 2010-2018. RESULTS: In 2018, an estimated 66.9% of U.S. adults aged 50-75 years had a CRC screening test within recommended time intervals. However, the prevalence was less than 50% among those aged 50-54 years, those without a usual source of health care, those with no doctor visits in the past year, and those who were uninsured. The test types most commonly used within recommended time intervals were colonoscopy within 10 years (61.1%), FOBT or FIT in the past year (8.8%), and FIT-DNA within 3 years (2.7%). After age-standardization to the 2010 census population, the percentage up-to-date with CRC screening increased from 61.2% in 2015 to 65.3% in 2018, driven by increased use of stool testing, including FIT-DNA. CONCLUSIONS: These results show some progress, driven by a modest increase in stool testing. However, CRC testing remains low in many population subgroups. IMPACT: These results can inform efforts to achieve population CRC screening goals. |
Risk of cervical precancer and cancer among uninsured and underserved women from 2009 to 2017
Saraiya M , Cheung LC , Soman A , Mix J , Kenney K , Chen X , Perkins RB , Schiffman M , Wentzensen N , Miller J . Am J Obstet Gynecol 2020 224 (4) 366 e1-366 e32 BACKGROUND: New guidelines for managing cervical precancer among women in the United States use risk directly to guide clinical actions for individuals who are being screened. These risk-based management guidelines have previously only been based on risks from a large integrated healthcare system. We present here data representative of women of low income without continuous insurance coverage to inform the 2019 guidelines and ensure applicability. OBJECTIVE: We examined the risks of high-grade precancer after human papillomavirus and cytology tests in underserved women and assessed the applicability of the 2019 guidelines to this population. STUDY DESIGN: We examined cervical cancer screening and follow-up data among 363,546 women enrolled in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program from 2009 to 2017. We estimated the immediate (prevalent) risks of cervical intraepithelial lesion grade 3 or cancer by using prevalence-incidence mixture models. Risks were estimated for each combination of human papillomavirus and cytology result and were stratified by screening history. We compared these risks with published estimates used in new risk-based management guidelines. RESULTS: Women who were up-to-date with their screening, defined as being screened with cytology within the past 5 years, had immediate risks of cervical intraepithelial neoplasia grade 3 or higher similar to that of women at Kaiser Permanente Northern California, whose data were used to develop the management guidelines. However, women in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program had greater immediate risks if they were never screened or not up-to-date with their screening. CONCLUSION: New cervical risk-based management guidelines are applicable for underinsured and uninsured women with a low income in the United States who are up-to-date with their screening. The increased risk observed here among women who received human papillomavirus-positive, high-grade cytology results, who were never screened, or who were not up-to-date with their cervical cancer screening, led to a recommendation in the management guidelines for immediate treatment among these women. |
Neurochemical and neurobiological weapons
Sejvar JJ . Neurol Clin 2020 38 (4) 881-896 Nerve agents and neurobiological weapons are among the most devastating and lethal of weapons. Acetylcholinesterase inhibitors act by increasing the amount of acetylcholine in the neuromuscular junction, resulting in flaccid paralysis. Tabun, VX, soman, and sarin are the major agents in this category. Exposure to nerve agents can be inhalational or through dermal contact. Neurotoxins may have peripheral and central effects on the nervous system. Atropine is an effective antidote to nerve agents. Neurobiological weapons entail using whole organisms or organism-synthesized toxins as agents. Some organisms that can be used as biological weapons include smallpox virus. |
Screening for lung cancer - 10 states, 2017
Richards TB , Soman A , Thomas CC , VanFrank B , Henley SJ , Gallaway MS , Richardson LC . MMWR Morb Mortal Wkly Rep 2020 69 (8) 201-206 Lung cancer is the leading cause of cancer death in the United States; 148,869 lung cancer-associated deaths occurred in 2016 (1). Mortality might be reduced by identifying lung cancer at an early stage when treatment can be more effective (2). In 2013, the U.S. Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low-dose computed tomography (CT) for adults aged 55-80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years (2).(dagger) This was a Grade B recommendation, which required health insurance plans to cover lung cancer screening as a preventive service.( section sign) To assess the prevalence of lung cancer screening by state, CDC used Behavioral Risk Factor Surveillance System (BRFSS) data( paragraph sign) collected in 2017 by 10 states. Overall, 12.7% adults aged 55-80 years met the USPSTF criteria for lung cancer screening. Among those meeting USPSTF criteria, 12.5% reported they had received a CT scan to check for lung cancer in the last 12 months. Efforts to educate health care providers and provide decision support tools might increase recommended lung cancer screening. |
Perceived risk of colorectal and breast cancers among women who are overweight or with obesity
Hall IJ , Soman A , Smith JL , White A , Crawford A . Prev Med Rep 2019 14 (100845) 100845 Many overweight women or women with obesity do not acknowledge their high weight status and may be unaware of their elevated cancer risk. We explored the relationship between weight status and women's perceived risk of colorectal (CRC) and breast cancers, overall and by race/ethnicity, in a nationally representative sample. Data was combined from NHIS 2005, 2010, and 2015 sample adult questionnaires and cancer control supplements. The analytic sample included females aged 18 years and over without reported history of cancer diagnosis. Multivariable logistic regression was performed and adjusted estimates for perceived risk of CRC and breast cancers were examined, stratified by body mass index and race/ethnicity. Data were reported using predicted marginal risk ratio (PMR). Colorectal cancer risk perception remained lowest among Non-Hispanic (NH) Black women regardless of weight status (PMR = 0.53 obesity, 0.65 overweight, 0.55 normal) compared to NH White women after adjustment for all covariates. Hispanic women who were overweight or had obesity also saw themselves at lower risk of CRC compared to NH White women, however these findings were statistically insignificant. Breast cancer risk perception also remained low for NH Blacks and Hispanics at any weight compared with NH Whites. Greater effort is needed to develop, disseminate, and widely adopt or institutionalize multilevel weight management interventions and programs. These programs increase awareness of excess weight as a risk factor for cancer and empower women in diverse communities to achieve and maintain a healthy weight by adopting healthy behaviors related to nutrition and physical activity. |
Lung cancer screening inconsistent with U.S. Preventive Services Task Force recommendations
Richards TB , Doria-Rose VP , Soman A , Klabunde CN , Caraballo RS , Gray SC , Houston KA , White MC . Am J Prev Med 2018 56 (1) 66-73 INTRODUCTION: Prior studies suggest overuse of nonrecommended lung cancer screening tests in U.S. community practice and underuse of recommended tests. METHODS: Data from the 2010 and 2015 National Health Interview Surveys was analyzed from 2016 to 2018. Prevalence, populations, and number of chest computed tomography (CT) and chest x-ray tests were estimated for people who did and did not meet U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening, among people aged >/=40 years without lung cancer. RESULTS: In 2015, among those who met USPSTF criteria, 4.4% (95% CI=3.0%, 6.6%), or 360,000 (95% CI=240,000, 535,000) people reported lung cancer screening with a chest CT; and 8.5% (95% CI=6.5%, 11.1%), or 689,000 (95% CI=526,000, 898,000) people reported a chest x ray. Among those who did not meet USPSTF criteria, 2.3% (95% CI=2.0%, 2.6%), or 3,259,000 (95% CI=2,850,000, 3,724,000) people reported a chest x ray; and 1.3% (95% CI=1.1%, 1.5%), or 1,806,000 (95% CI=1,495,000, 2,173,000) people reported a chest CT. The estimated population meeting USPSTF criteria for lung cancer screening in 2015 was 8,098,000 (95% CI=7,533,000, 8,702,000), which was smaller than the 9,620,000 people (95% CI=8,960,000, 10,325,000) in 2010. CONCLUSIONS: The number of adults inappropriately screened for lung cancer greatly exceeds the number screened according to USPSTF recommendations, the prevalence of appropriate lung cancer screening is low, and the population meeting USPSTF criteria is shrinking. To realize the potential benefits of screening, better processes to appropriately triage eligible individuals to screening, plus screening with a USPSTF-recommended test, would be beneficial. |
Investigation of dried blood sampling with liquid chromatography tandem mass spectrometry to confirm human exposure to nerve agents
Shaner RL , Coleman RM , Schulze N , Platanitis K , Brown AA , Seymour C , Kaplan P , Perez J , Hamelin EI , Johnson RC . Anal Chim Acta 2018 1033 100-107 A method was developed to detect and quantify organophosphate nerve agent (OPNA) metabolites in dried blood samples. Dried blood spots (DBS) and microsampling devices are alternatives to traditional blood draws, allowing for safe handling, extended stability, reduced shipping costs, and potential self-sampling. DBS and microsamplers were evaluated for precision, accuracy, sensitivity, matrix effects, and extraction recovery following collection of whole blood containing five OPNA metabolites. The metabolites of VX, Sarin (GB), Soman (GD), Cyclosarin (GF), and Russian VX (VR) were quantitated from 5.0 to 500 ng mL-1 with precision of <=16% and accuracy between 93 and 108% for QC samples with controlled volumes. For unknown spot volumes, OPNA metabolite concentrations were normalized to total blood protein to improve interpretation of nerve agent exposures. This study provides data to support the use of DBS and microsamplers to collect critical exposure samples quickly, safely, and efficiently following large-scale chemical exposure events. |
Factors associated with breast MRI use among women with a family history of breast cancer
White MC , Soman A , Weinberg CR , Rodriguez JL , Sabatino SA , Peipins LA , DeRoo L , Nichols HB , Hodgson ME , Sandler DP . Breast J 2018 24 (5) 764-771 Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk >/= 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications. |
Communicating with daughters about familial risk of breast cancer: Individual, family, and provider influences on women's knowledge of cancer risk
Peipins LA , Rodriguez JL , Hawkins NA , Soman A , White MC , Hodgson ME , DeRoo LA , Sandler DP . J Womens Health (Larchmt) 2018 27 (5) 630-639 INTRODUCTION: Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. MATERIALS AND METHODS: Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. RESULTS: We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. CONCLUSIONS: Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer. |
Relationship between serum trimethylamine N-oxide and exposure to dioxin-like pollutants
Petriello MC , Charnigo R , Sunkara M , Soman S , Pavuk M , Birnbaum L , Morris AJ , Hennig B . Environ Res 2018 162 211-218 Trimethylamine N-oxide (TMAO) is a diet and gut microbiota-derived metabolite that has been linked to cardiovascular disease risk in human studies and animal models. TMAO levels show wide inter and intra individual variability in humans that can likely be accounted for by multiple factors including diet, the gut microbiota, levels of the TMAO generating liver enzyme Flavin-containing monooxygenase 3 (FMO3) and kidney function. We recently found that dioxin-like (DL) environmental pollutants increased FMO3 expression to elevate circulating diet-derived TMAO in mice, suggesting that exposure to this class of pollutants might also contribute to inter-individual variability in circulating TMAO levels in humans. To begin to explore this possibility we examined the relationship between body burden of DL pollutants (reported by serum lipid concentrations) and serum TMAO levels (n = 340) in the Anniston, AL cohort, which was highly exposed to polychlorinated biphenyls (PCBs). TMAO concentrations in archived serum samples from the Anniston Community Health Survey (ACHS-II) were measured, and associations of TMAO with 28 indices of pollutant body burden, including total dioxins toxic equivalent (TEQ), were quantified. Twenty-three (22 after adjustment for multiple comparisons) of the 28 indices were significantly positively associated with TMAO. Although the design of ACHS-II does not enable quantitative assessment of the contributions of previously known determinants of TMAO variability to this relationship, limited multivariate modeling revealed that total dioxins TEQ was significantly associated with TMAO among females (except at high BMIs) but not among males. Our results from this cross-sectional study indicate that exposure to DL pollutants may contribute to elevated serum TMAO levels. Prospective longitudinal studies will be required to assess the joint relationship between DL pollutant exposures, other determinants of TMAO, and health outcomes. |
Use of hupresin to capture red blood cell acetylcholinesterase for detection of soman exposure
Onder S , Schopfer LM , Cashman JR , Tacal O , Johnson RC , Blake TA , Lockridge O . Anal Chem 2018 90 (1) 974-979 Toxicity from acute exposure to nerve agents and organophosphorus toxicants is due to irreversible inhibition of acetylcholinesterase (AChE) in the nervous system. AChE in red blood cells is a surrogate for AChE in the nervous system. Previously we developed an immunopurification method to enrich red blood cell AChE (RBC AChE) as a biomarker of exposure. The goal of the present work was to provide an alternative RBC AChE enrichment strategy, by binding RBC AChE to Hupresin affinity gel. AChE was solubilized from frozen RBC by addition of 1% Triton X-100. Insoluble debris was removed by centrifugation. The red, but not viscous, RBC AChE solution was loaded on a Hupresin affinity column. Hemoglobin and other proteins were washed off with 3 M NaCl, while retaining AChE bound to Hupresin. Denatured AChE was eluted with 1% trifluoroacetic acid. The same protocol was used for 20 mL of RBC AChE inhibited with a soman model compound. The acid denatured protein was digested with pepsin and analyzed by liquid chromatography tandem mass spectrometry on a 6600 Triple-TOF mass spectrometer. A targeted method identified the aged soman adduct on serine 203 in peptide FGESAGAAS. It was concluded that Hupresin can be used to enrich soman-inhibited AChE solubilized from 8 mL of frozen human erythrocytes, yielding a quantity sufficient for detecting soman exposure. |
Immunopurification of acetylcholinesterase from red blood cells for detection of nerve agent exposure
Dafferner AJ , Schopfer LM , Xiao G , Cashman JR , Yerramalla U , Johnson RC , Blake TA , Lockridge O . Chem Res Toxicol 2017 30 (10) 1897-1910 Nerve agents and organophosphorus pesticides make a covalent bond with the active site serine of acetylcholinesterase (AChE), resulting in inhibition of AChE activity and toxic symptoms. AChE in red blood cells (RBCs) serves as a surrogate for AChE in the nervous system. Mass spectrometry analysis of adducts on RBC AChE could provide evidence of exposure. Our goal was to develop a method of immunopurifying human RBC AChE in quantities adequate for detecting exposure by mass spectrometry. For this purpose, we immobilized 3 commercially available anti-human acetylcholinesterase monoclonal antibodies (AE-1, AE-2, and HR2) plus 3 new monoclonal antibodies. The monoclonal antibodies were characterized for binding affinity, epitope mapping by pairing analysis, and nucleotide and amino acid sequences. AChE was solubilized from frozen RBCs with 1% (v/v) Triton X-100. A 16 mL sample containing 5.8 mug of RBC AChE was treated with a quantity of soman model compound that inhibited 50% of the AChE activity. Native and soman-inhibited RBC AChE samples were immunopurified on antibody-Sepharose beads. The immunopurified RBC AChE was digested with pepsin and analyzed by liquid chromatography tandem mass spectrometry on a 6600 Triple-TOF mass spectrometer. The aged soman-modified PheGlyGluSerAlaGlyAlaAlaSer (FGESAGAAS) peptide was detected using a targeted analysis method. It was concluded that all 6 monoclonal antibodies could be used to immunopurify RBC AChE and that exposure to nerve agents could be detected as adducts on the active site serine of RBC AChE. |
Surveillance of high-grade cervical cancer precursors (CIN III/AIS) in four population-based cancer registries, United States, 2009-2012
Watson M , Soman A , Flagg EW , Unger E , Deapen D , Chen VW , Peres LC , Copeland G , Tucker TC , Garnett E , Saraiya M . Prev Med 2017 103 60-65 Surveillance of cervical intraepithelial neoplasia grade III (CIN III) and adenocarcinoma in situ (AIS) is important for determining the burden of a preventable disease, identifying effects of vaccination on future diagnoses, and developing targeted programs. We analyzed population-based rates of high-grade cervical cancer precursor lesions using data from four central cancer registries (diagnosis years 2009-2012 from Louisiana, Kentucky, Michigan, and diagnosis years 2011-2012 from Los Angeles) by age, race, and histology. We also compared rates of precursors to invasive cancers. With 4 complete years of data from Michigan, we were able to conduct a trend analysis for that state. Data analysis was conducted in Atlanta during 2016. Kentucky reported the highest rate of CIN III/AIS (69.8), followed by Michigan (55.4), Louisiana (42.3), and Los Angeles (19.2). CIN III/AIS rates declined among women in Michigan by 37% each year for women aged 15-19, 14% for those aged 20-24, and 7% for those aged 25-29. Rates of CIN III/AIS vary by registry, and were higher than invasive cancer. In Michigan, declines in CIN III/AIS among women aged 15-29 are likely related in part to updated screening recommendations, and to the impact of human papillomavirus vaccination. |
Use of medications for treating anxiety and depression in cancer survivors in the United States
Hawkins NA , Soman A , Buchanan Lunsford N , Leadbetter S , Rodriguez JL . J Clin Oncol 2017 35 (1) 78-85 Purpose This study used population-based data to estimate the percentage of cancer survivors in the United States reporting current medication use for anxiety and depression and to characterize the survivors taking this type of medication. Rates of medication use in cancer survivors were compared with rates in the general population. Methods We analyzed data from the National Health Interview Survey, years 2010 to 2013, identifying cancer survivors (n = 3,184) and adults with no history of cancer (n = 44,997) who completed both the Sample Adult Core Questionnaire and the Adult Functioning and Disability Supplement. Results Compared with adults with no history of cancer, cancer survivors were significantly more likely to report taking medication for anxiety (16.8% v 8.6%, P < .001), depression (14.1% v 7.8%, P < .001), and one or both of these conditions combined (19.1% v 10.4%, P < .001), indicating that an estimated 2.5 million cancer survivors were taking medication for anxiety or depression in the United States at that time. Survivor characteristics associated with higher rates of medication use for anxiety included being younger than 65 years old, female, and non-Hispanic white, and having public insurance, a usual source of medical care, and multiple chronic health conditions. Survivor characteristics associated with medication use for depression were largely consistent with those for anxiety, with the exceptions that insurance status was not significant, whereas being widowed/divorced/separated was associated with more use. Conclusion Cancer survivors in the United States reported medication use for anxiety and depression at rates nearly two times those reported by the general public, likely a reflection of greater emotional and physical burdens from cancer or its treatment. |
Heart disease and cancer deaths - trends and projections in the United States, 1969-2020
Weir HK , Anderson RN , Coleman King SM , Soman A , Thompson TD , Hong Y , Moller B , Leadbetter S . Prev Chronic Dis 2016 13 E157 INTRODUCTION: Heart disease and cancer are the first and second leading causes of death in the United States. Age-standardized death rates (risk) have declined since the 1960s for heart disease and for cancer since the 1990s, whereas the overall number of heart disease deaths declined and cancer deaths increased. We analyzed mortality data to evaluate and project the effect of risk reduction, population growth, and aging on the number of heart disease and cancer deaths to the year 2020. METHODS: We used mortality data, population estimates, and population projections to estimate and predict heart disease and cancer deaths from 1969 through 2020 and to apportion changes in deaths resulting from population risk, growth, and aging. RESULTS: We predicted that from 1969 through 2020, the number of heart disease deaths would decrease 21.3% among men (-73.9% risk, 17.9% growth, 34.7% aging) and 13.4% among women (-73.3% risk, 17.1% growth, 42.8% aging) while the number of cancer deaths would increase 91.1% among men (-33.5% risk, 45.6% growth, 79.0% aging) and 101.1% among women (-23.8% risk, 48.8% growth, 76.0% aging). We predicted that cancer would become the leading cause of death around 2016, although sex-specific crossover years varied. CONCLUSION: Risk of death declined more steeply for heart disease than cancer, offset the increase in heart disease deaths, and partially offset the increase in cancer deaths resulting from demographic changes over the past 4 decades. If current trends continue, cancer will become the leading cause of death by 2020. |
Evaluation of multiple blood matrices for assessment of human exposure to nerve agents
Schulze ND , Hamelin EI , Winkeljohn WR , Shaner RL , Basden BJ , deCastro BR , Pantazides BG , Thomas JD , Johnson RC . J Anal Toxicol 2016 40 (3) 229-35 Biomedical samples may be used to determine human exposure to nerve agents through the analysis of specific biomarkers. Samples received may include serum, plasma, whole blood, lysed blood and, due to the toxicity of these compounds, postmortem blood. To quantitate metabolites resulting from exposure to sarin (GB), soman (GD), cyclosarin (GF), VX and VR, these blood matrices were evaluated individually for precision, accuracy, sensitivity and specificity. Accuracies for these metabolites ranged from 100 to 113% with coefficients of variation ranging from 2.31 to 13.5% across a reportable range of 1-100 ng/mL meeting FDA recommended guidelines for bioanalytical methods in all five matrices. Limits of detection were calculated to be 0.09-0.043 ng/mL, and no interferences were detected in unexposed matrix samples. The use of serum calibrators was also determined to be a suitable alternative to matrix-matched calibrators. Finally, to provide a comparative value between whole blood and plasma, the ratio of the five nerve agent metabolites measured in whole blood versus plasma was determined. Analysis of individual whole blood samples (n = 40), fortified with nerve agent metabolites across the reportable range, resulted in average nerve agent metabolite blood to plasma ratios ranging from 0.53 to 0.56. This study demonstrates the accurate and precise quantitation of nerve agent metabolites in serum, plasma, whole blood, lysed blood and postmortem blood. It also provides a comparative value between whole blood and plasma samples, which can assist epidemiologists and physicians with interpretation of test results from blood specimens obtained under variable conditions. |
Reply to it is not all black and white: Future incidence of stomach cancer will be substantially higher than projected due to the effects of immigration and increasing Hispanic and Asian populations in the United States
Weir HK , Thompson TD , Soman A , Møller B , Leadbetter S . Cancer 2015 121 (23) 4267-8 Drs. Hillard and Graham have provided thoughtful comments on our article,1 and we agree that we might have underestimated the projected incidence of stomach cancer. As they note, the results of our analyses were limited to the 2 major racial groups in the United States (blacks and whites) and did not include predictions of the cancer burden for other racial and ethnic groups. The age-period-cohort models that we used require a minimum of 20 years of incidence data to generate reasonable estimates for predicting future trends in cancer incidence.2 The data for these models came from 9 Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries, which cover approximately 10% of the US population.3 In more recent years, both SEER registries and those participating in the Centers for Disease Control and Prevention’s National Program of Cancer Registries have been collecting more detailed information regarding race, including Asian/Pacific Islander subpopulations and ethnicity (Hispanic and non-Hispanic).4 In addition, cancer registries are now in all 50 states and the District of Columbia.4 In the future, with expanded population coverage and more detailed information concerning race and ethnicity, it will be possible to predict the cancer incidence burden for Asian/Pacific Islander and Hispanic individuals and thus improve the projections for cancers that disproportionately impact these populations. | | The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. |
Meeting the Healthy People 2020 objectives to reduce cancer mortality
Weir HK , Thompson TD , Soman A , Moller B , Leadbetter S , White MC . Prev Chronic Dis 2015 12 E104 INTRODUCTION: Healthy People 2020 (HP2020) calls for a 10% to 15% reduction in death rates from 2007 to 2020 for selected cancers. Trends in death rates can be used to predict progress toward meeting HP2020 targets. METHODS: We used mortality data from 1975 through 2009 and population estimates and projections to predict deaths for all cancers and the top 23 cancers among men and women by race. We apportioned changes in deaths from population risk and population growth and aging. RESULTS: From 1975 to 2009, the number of cancer deaths increased among white and black Americans primarily because of an aging white population and a growing black population. Overall, age-standardized cancer death rates (risk) declined in all groups. From 2007 to 2020, rates are predicted to continue to decrease while counts of deaths are predicted to increase among men (15%) and stabilize among women (increase <10%). Declining death rates are predicted to meet HP2020 targets for cancers of the female breast, lung and bronchus, cervix and uterus, colon and rectum, oral cavity and pharynx, and prostate, but not for melanoma. CONCLUSION: Cancer deaths among women overall are predicted to increase by less than 10%, because of, in part, declines in breast, cervical, and colorectal cancer deaths among white women. Increased efforts to promote cancer prevention and improve survival are needed to counter the impact of a growing and aging population on the cancer burden and to meet melanoma target death rates. |
The past, present, and future of cancer incidence in the United States: 1975 through 2020
Weir HK , Thompson TD , Soman A , Moller B , Leadbetter S . Cancer 2015 121 (11) 1827-37 BACKGROUND: The overall age-standardized cancer incidence rate continues to decline whereas the number of cases diagnosed each year increases. Predicting cancer incidence can help to anticipate future resource needs, evaluate primary prevention strategies, and inform research. METHODS: Surveillance, Epidemiology, and End Results data were used to estimate the number of cancers (all sites) resulting from changes in population risk, age, and size. The authors projected to 2020 nationwide age-standardized incidence rates and cases (including the top 23 cancers). RESULTS: Since 1975, incident cases increased among white individuals, primarily caused by an aging white population, and among black individuals, primarily caused by an increasing black population. Between 2010 and 2020, it is expected that overall incidence rates (proxy for risk) will decrease slightly among black men and stabilize in other groups. By 2020, the authors predict annual cancer cases (all races, all sites) to increase among men by 24.1% (-3.2% risk and 27.3% age/growth) to >1 million cases, and by 20.6% among women (1.2% risk and 19.4% age/growth) to >900,000 cases. The largest increases are expected for melanoma (white individuals); cancers of the prostate, kidney, liver, and urinary bladder in males; and the lung, breast, uterus, and thyroid in females. CONCLUSIONS: Overall, the authors predict cancer incidence rates/risk to stabilize for the majority of the population; however, they expect the number of cancer cases to increase by >20%. A greater emphasis on primary prevention and early detection is needed to counter the effect of an aging and growing population on the burden of cancer. |
Reply to Soman et al, Alffenaar et al, Metcalfe et al, and Raoult
Cegielski JP , Chen MP , Tupasi TE , Leimane V , Volchenkov GV . Clin Infect Dis 2014 60 (6) 971-3 We thank Metcalfe et al, Alffenaar et al, Soman et al, and Raoult for their interest in our study [1]. Metcalfe et al raise 2 issues about the analysis and reporting of results [2]. Alffenaar and colleagues raise issues related to drug dosing [3]. Soman and colleagues raise concern about standardized treatment regimens [4]. Raoult refers to the potential utility of existing drugs that are not standard antituberculosis drugs [5]. We respond to each of these letters in turn. | Metcalfe and colleagues suggest that patients who remain culture negative after 1 month of treatment could not have acquired drug resistance and therefore might have been included in the denominator when calculating the proportion of patients with acquired drug resistance [2]. However, the reality and the math are more complicated for at least 3 reasons. First, we disagree that the target population “is presented as all patients with MDR [multidrug-resistant] tuberculosis starting treatment with [second-line drugs].” The target population for this analysis was patients with at least one positive follow-up cultures as displayed in our Figure 1 [1]. Second, we described the excluded subset of patients as having no positive follow-up cultures rather than as having all negative follow-up cultures because these are not the same: 20.8% of the excluded group of patients did not complete treatment (ie, were classified as defaulting) after a median of <12 months (interquartile range, 5–16 months). Because “default” is a World Health Organization (WHO)–defined standard outcome category [6], it was the endpoint in our follow-up of these patients, and we cannot know whether these patients had any subsequent positive cultures. However, the duration of treatment for this group of patients is inadequate. These patients would be at high risk for again becoming culture positive and for acquired drug resistance. Third, many of these patients already had baseline resistance to fluoroquinolones, second-line injectable drugs, or both. It would not be appropriate to include them in the denominator when calculating the frequency of acquired resistance to these same drugs. The exact percentages are uncertain because we did not receive baseline cultures for all these patients and did not recover viable mycobacteria from all cultures received. However, of the 340 viable baseline isolates we received among patients with no positive follow-up cultures, 6.8% had fluoroquinolone resistance, 8.5% had resistance to 1 or more second-line injectable drugs, 11.8% had resistance to either, and 3.5% had resistance to both. |
Simultaneous measurement of tabun, sarin, soman, cyclosarin, VR, VX, and VM adducts to tyrosine in blood products by isotope dilution UHPLC-MS/MS
Crow BS , Pantazides BG , Quinones-Gonzalez J , Garton JW , Carter MD , Perez JW , Watson CM , Tomcik DJ , Crenshaw MD , Brewer BN , Riches JR , Stubbs SJ , Read RW , Evans RA , Thomas JD , Blake TA , Johnson RC . Anal Chem 2014 86 (20) 10397-405 This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 muL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100-50.0 ng/mL for GB- and VR-Tyr and 0.250-50.0 ng/mL for GA-, GD-, GF-, and VX/VM-Tyr (R2 ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA-, GB-, GD-, GF-, VR-, and VX/VM-Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence. |
Quantitation of five organophosphorus nerve agent metabolites in serum using hydrophilic interaction liquid chromatography and tandem mass spectrometry
Hamelin EI , Schulze ND , Shaner RL , Coleman RM , Lawrence RJ , Crow BS , Jakubowski EM , Johnson RC . Anal Bioanal Chem 2014 406 (21) 5195-202 Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman), and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid-phase extraction coupled with high-performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3 to 0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101-105 %) and high precision (5-8 %) for the detection of these five nerve agent hydrolysis products in serum. |
Gender disparity between cutaneous and non-cutaneous manifestations of Lyme borreliosis
Strle F , Wormser GP , Mead P , Dhaduvai K , Longo MV , Adenikinju O , Soman S , Tefera Y , Maraspin V , Lotric-Furlan S , Ogrinc K , Cimperman J , Ruzic-Sabljic E , Stupica D . PLoS One 2013 8 (5) e64110 Cutaneous manifestations of Lyme borreliosis in Europe include erythema migrans (EM) and acrodermatitis chronica atrophicans (ACA); the most common non-cutaneous manifestations are Lyme neuroborreliosis (LNB) and Lyme arthritis. The purpose of this study was to evaluate the gender distribution of patients with these clinical manifestations of Lyme borreliosis. Data on gender were obtained from the clinical records of patients with Lyme borreliosis aged ≥15 years who had been evaluated at the University Medical Center Ljubljana, Ljubljana, Slovenia. Among 10,539 patients diagnosed with EM, 6,245 (59.3%) were female and among 506 ACA patients 347 (68.6%) were female. In contrast, among the 60 patients with Lyme arthritis only 15 (25%) were female (p<0.0001 for the comparison of gender with EM or ACA) and among the 130 patients with LNB only 51 (39.2%) were females (p<0.0001 for the comparison of gender with EM or ACA). Although the proportion that was female in the LNB group was greater than that of patients with Lyme arthritis, this difference did not reach statistical significance (p = 0.10). Although older individuals are more likely to be female in the general Slovenian population, the age of patients with cutaneous versus non-cutaneous manifestations was not the explanation for the observed differences in gender. In conclusion, patients with cutaneous manifestations of Lyme borreliosis were predominantly female, whereas those with non-cutaneous manifestations were predominantly male. This provocative finding is unexplained but may have direct relevance to the pathogenesis of Lyme borreliosis. |
Comparison of high-resolution and tandem mass spectrometry for the analysis of nerve agent metabolites in urine
Hamelin EI , Bragg W , Shaner RL , Swaim LL , Johnson RC . Rapid Commun Mass Spectrom 2013 27 (15) 1697-704 RATIONALE: Although use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. High-resolution mass spectrometry (HRMS) was compared to tandem mass spectrometry (MS/MS) analysis for the quantitation of five urinary metabolites specific to VX, Russian VX, soman, sarin and cyclosarin nerve agents. The HRMS method was further evaluated for qualitative screening of metabolites not included in the test panel. METHODS: Nerve agent metabolites were extracted from urine using solid-phase extraction, separated using hydrophilic interaction chromatography and analyzed using both tandem and high-resolution mass spectrometry. MS/MS results were obtained using selected reaction monitoring with unit resolution; HRMS results were obtained using a mass extraction window of 10 ppm at a mass resolution of 50 000. The benchtop Orbitrap HRMS instrument was operated in full scan mode, to measure the presence of unexpected nerve agent metabolites. RESULTS: The assessment of two quality control samples demonstrated high accuracy (99.5-104%) and high precision (2-9%) for both HRMS and MS/MS. Sensitivity, as described by the limit of detection, was overlapping for both detectors (0.2-0.7 ng/mL). Additionally, the HRMS method positively confirmed the presence of a nerve agent metabolite, not included in the test panel, using the accurate mass and relative retention time. CONCLUSIONS: The precision, accuracy, and sensitivity were comparable between the current MS/MS method and this newly developed HRMS analysis for five nerve agent metabolites. HRMS showed additional capabilities beyond the current method by confirming the presence of a metabolite not included in the test panel. |
Cervical cancer screening among young adult women in the United States
Roland KB , Benard V , Soman A , Breen N , Kepka D , Saraiya M . Cancer Epidemiol Biomarkers Prev 2013 22 (4) 580-8 BACKGROUND: Cervical cancer screening guidelines have evolved significantly in the last decade for young adult women, with current recommendations promoting later initiation and longer intervals. METHODS: Using self-reported cross-sectional National Health Interview Survey (NHIS) 2000-2010 data, trends in Papanicolaou (Pap) testing among women aged 18-29 years were examined. NHIS 2010 data were used to investigate age at first Pap test (N=2,198), time since most recent Pap test (n=1,622), and predictors of Pap testing within the last 12 months (n=1,622). RESULTS: The percentage of 18-year-olds who reported ever having a Pap test significantly decreased from 49.9% in 2000 to 37.9% in 2010. Mean age at first Pap test in 2010 was significantly younger for non-Hispanic black women (16.9 years), women <high school education (16.9 years), women who received the HPV vaccine (17.1 years), and women who have ever given birth (17.3 years). The majority reported their last Pap test within the previous 12 months (73.1%). Usual source of healthcare (OR 2.31) and current birth control use (OR 1.64) significantly increased chances of having a Pap test within the previous 12 months. CONCLUSIONS: From 2000 to 2010 there was a gradual decline in Pap test initiation among 18-year-olds, however, in 2010 many women reported ≤12 months since last screening. Evidence-based guidelines should be promoted, as screening young adult women for cervical cancer more frequently than recommended can cause considerable harms. IMPACT: A baseline of cervical cancer screening among young adult women in the United States to assess adherence to evidence-based screening guidelines. |
Reproductive patterns among mothers of males diagnosed with Duchenne or Becker muscular dystrophy.
Nabukera SK , Romitti PA , Caspers KM , Street N , Cunniff C , Mathews KD , Fox DJ , Puzhankara S , Ciafaloni E , James KA , Su Y . Am J Med Genet A 2013 161 (1) 70-75 Diagnosis of a child with Duchenne or Becker muscular dystrophy (DBMD) may impact future maternal reproductive choice; however, little is known about the reproductive patterns of mothers with a male child diagnosed with DBMD. Using population-based surveillance data collected by the muscular dystrophy surveillance, tracking, and research network, the proportion of mothers who conceived and delivered a live birth following the diagnosis of DBMD in an affected male child and factors associated with such reproductive choice were identified. To accomplish this, maternal demographic data were linked to birth certificate data to construct the reproductive history for 239 mothers. Univariable and bivariable analyses were conducted to determine the proportion of mothers delivering a live birth and associated factors. By the time of the current study, 96 (40.2%) of the 239 mothers had at least one live birth following delivery of their oldest affected male child; 53 (22.2%) of these mothers had a live birth before and 43 (18.0%) had a live birth after DBMD diagnosis of a male child. Mothers with a live birth after diagnosis were significantly younger at diagnosis of the oldest affected male child (26.2 +/- 4.2 years vs. 31.5 +/- 5.5 years), and were less likely to be white non-Hispanic compared to those with no live birth after diagnosis. These results suggest that about one in five mothers deliver a live birth subsequent to DBMD diagnosis in a male child. Maternal age and race/ethnicity were associated with this reproductive choice. (c) 2012 Wiley Periodicals, Inc. |
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