IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

OBJECTIVE: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules. METHODS: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination. RESULTS: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels. CONCLUSION: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection. ABBREVIATIONS: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Occupational Injuries and Exposures among Emergency Medical Services Workers.

OBJECTIVE: Emergency medical services (EMS) workers incur occupational injuries at a higher rate than the general worker population. This study describes the circumstances of occupational injuries and exposures among EMS workers to guide injury prevention efforts. METHODS: The National Institute for Occupational Safety and Health collaborated with the National Highway Traffic Safety Administration to conduct a follow-back survey of injured EMS workers identified from a national sample of hospital emergency departments (EDs) from July 2010 through June 2014. The interviews captured demographic, employment, and injury event characteristics. The telephone interview data were weighted and are presented in the results as national estimates and rates. RESULTS: Telephone interviews were completed by 572 EMS workers treated in EDs, resulting in a 74% cooperation rate among all EMS workers who were identified and successfully contacted. Study respondents represented 89,100 (95% CI 54,400-123,800) EMS workers who sought treatment in EDs over the four-year period. Two-thirds were male (59,900, 95% CI 35,200-84,600) and 42% were 18-29 years old (37,300, 95% CI 19,700-54,700). Three-quarters of the workers were full-time (66,800, 95% CI 39,800-93,800) and an additional 10% were part-time or on-call (9,300, 95% 4,900-13,700). Among career EMS workers, the injury rate was 8.6 per 100 full-time equivalent EMS workers (95% CI 5.3-11.8). Over half of all injured workers had less than ten years of work experience. Sprains and strains accounted for over 40% of all injuries (37,000, 95% CI 22,000-52,000). Body motion injuries were the leading event (24,900, 95% CI 14,900-35,000), with 90% (20,500, 95% CI 12,800-32,100) attributed to lifting, carrying, or transferring a patient and/or equipment. Exposures to harmful substances were the second leading event (24,400, 95% CI 11,700-37,100). CONCLUSION: New and enhanced efforts to prevent EMS worker injuries are needed, especially those aimed at preventing body motion injuries and exposures to harmful substances. EMS and public safety agencies should consider adopting and evaluating injury prevention measures to improve occupational safety and promote the health, performance, and retention of the EMS workforce.

Hired crop worker injuries on farms in the United States: A comparison of two survey periods from the National Agricultural Workers Survey.

BACKGROUND: Hired crop workers in the United States are at high risk of occupational injury. Targeted surveillance is important for effective occupational safety efforts. METHODS: The National Agricultural Workers Survey was utilized to collect injury data during the years 1999, 2002-2004 (period I) and 2008-2010 (period II). RESULTS: The overall injury rate declined between the two periods from 4.3 to 2.9/100 per full-time week-based equivalents (FTEWB ). Injury rates remained high during both periods for those with greater than 20 years farm experience (3.6 and 3.8/100 FTEWB ) and pesticide handling work (4.9 and 5.0/100 FTEWB ). Overexertion, contact with objects and equipment, and falls from height were common during both periods. Older workers comprised a greater proportion of injury cases in period II. CONCLUSION: Overexertion that leads to sprains/strains, dangerous ladder use, and pesticide use should be targeted as important risk exposures on the farm.

Characterizing emergency department patients who reported work-related injuries and illnesses.

BACKGROUND: Per a Congressional directive and funding, this study describes worker and workplace characteristics of emergency department (ED) patients who reported their injury/illness to their employer. The study also responds to Congress's request to enumerate injured/ill self-employed workers and workers with chronic conditions. METHODS: We conducted a follow-back study on injured/ill workers, including self-employed, identified from a national ED surveillance system from June 2012 through December 2013. RESULTS: An estimated 3,357,000 (95%CI: 2,516,000-4,199,000) workers treated in EDs reported their injury/illness to their employer or were self-employed. Of those, 202,000 (95%CI: 133,000-272,000) had a chronic condition. Of all reporters, excluding self-employed, 77% indicated they received instructions as to whom to report. CONCLUSION: The study did not identify underreporting issues and revealed that medical records data may not be appropriate for assessing underreporting. Additional research is needed to examine workplace characteristics that encourage injury and illness reporting. Am. J. Ind. Med. 59:610-620, 2016. © 2016 Wiley Periodicals, Inc.

Using emergency department surveillance data to assess occupational injury and illness reporting by workers.

OBJECTIVE: Researchers from the National Institute for Occupational Safety and Health (NIOSH) share detailed methodologies from conducting two follow-back studies initiated in 2010 that were designed to assess whether workers reported their injuries and illnesses to their employers and to identify worker incentives and disincentives for reporting work-related injuries to employers. METHODOLOGY: Study respondents were sampled from the National Electronic Injury Surveillance System occupational supplement (NEISS-Work), an emergency department-based surveillance system. Telephone interviews were used to collect information directly from workers. OUTCOMES: Among persons treated in emergency departments who could be identified as working at the time of injury or illness, most reported their injury or illness to their employer. Our studies did not assess if these reported injuries and illnesses were recorded on the Occupational Safety and Health logs. DISCUSSION: Our approach suggests that emergency department-based surveillance data are limited in their utility to investigate underreporting among workers. Am. J. Ind. Med. 59:600-609, 2016. © 2016 Wiley Periodicals, Inc.

Reported work-related injuries and illnesses among Hispanic workers: Results from an emergency department surveillance system follow-back survey.

BACKGROUND: Research suggests Hispanic workers underreport injuries/illnesses to their employer. METHODS: The National Electronic Injury Surveillance System-occupational supplement was used to conduct a follow-back study of workers treated in emergency departments (EDs) from June 2012 through December 2013. RESULTS: An estimated 448,000 (95%CI 230,000-665,000) Hispanic workers treated in EDs for a work-related injury or illness were represented by 362 completed interviews. Of these, an estimated 443,000 (95%CI 228,000-657,000) workers reported the injury or illness to their employer or were self-employed. The majority had not heard of workers' compensation. Only 10% expected workers' compensation to cover their medical payment while 62% expected payment to be covered by their employer. CONCLUSION: We characterized our respondent workforce who reported their injury or illness. We determined that NEISS-Work data are not the most appropriate source to capture underreporting of work-related injuries and illnesses to employers among Hispanic workers. Am. J. Ind. Med. 59:621-629, 2016. © 2016 Wiley Periodicals, Inc.

Mutation detection using plasma circulating tumor DNA (ctDNA) in a cohort of asymptomatic adults at increased risk for cancer.

PURPOSE: The primary purpose of this study was to clinically evaluate circulating tumor DNA (ctDNA) with a nine gene, 96 mutation panel among subjects at increased risk for cancer with no previous cancer diagnosis. SUBJECTS AND METHODS: DNA from 1059 asymptomatic subjects was analyzed for detection of low levels ctDNA using a blood plasma liquid biopsy assay. Subjects with detectable copies of ctDNA were asked to provide additional blood samples and relevant medical records throughout their one-year of participation. Subjects with a negative result were followed-up at one-year with a questionnaire. RESULTS: Mutations were detected in 58 subjects and not detected in 1001 subjects. Among the subjects who tested positive for one or more mutations, four were diagnosed with cancer, two of which through study-triggered clinical follow-up. Two subjects who tested negative on the screen received an early cancer diagnosis over the course of the year. The sensitivity of the assay at a threshold of ≥2 copies in this population was 66.67% and specificity was 94.87%. While the negative predictive value was 99.8%, the positive predictive value was only 6.9% in this cohort. Analysis of buffy coat DNA from eight positive subjects, including one who was diagnosed with cancer, revealed matching mutations suggesting that the ctDNA could have been derived from clonal hematopoiesis. CONCLUSION: The observed false positive rate of ctDNA on a 96-mutation assay in an asymptomatic high-risk population is much greater than the true positive rate, limiting its usefulness as a cancer screening tool in its current form.

Tumor-associated DNA mutation detection in individuals undergoing colonoscopy.

The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. Two hundred patients without a history of nonskin cancer had blood drawn before a colonoscopy. Plasma ctDNA was measured with a 96 mutation panel for nine cancer driver genes. The ctDNA results were correlated with the findings at colonoscopy. Of the 200 patients, 176 (88%) had wild-type DNA, 12 (6%) had mutations detected, and 12 (6%) had indeterminate results. Colonoscopy was normal in 80% of the patients and 20% were found to have polyps. No CRC was found in this study, precluding a determination of true-positive rate for CRC detection. Our ctDNA panel was positive in 13.2% of patients with colonic polyps found at colonoscopy, while 4.7% of patients with normal colonoscopy also had ctDNA detected, which may represent ctDNA released from a benign process, an occult tumor, or an acquired somatic mutation from clonal hematopoiesis.

Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study.

AIM: To compare pharmacogenetic test predictions with self-reported treatment experience and side effect tolerability among patients with depression taking psychotherapeutic medications. METHODS: Subjects completed a survey recalling medication effectiveness and side effects and then underwent pharmacogenetic testing. RESULTS: Our 15 gene pharmacogenetic panel predicted efficacy (p < 0.001) but did not predict side effect tolerability (p = 0.70) in a group of 352 patients. The pharmacogenetic panel and reported efficacy corresponded 60% of the time and medication tolerability agreed 71% of the time. CONCLUSION: Pharmacogenetic testing may be a useful adjunct to predict efficacy of medications used to treat depression.