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OBJECTIVE: The objective of this study was to update the mortality experience of a cohort of workers with and without potential exposure to acrylamide (AMD) at three U.S. plants (n = 8508) and one plant in The Netherlands (n = 344). METHODS: We computed standardized mortality ratios (SMRs) using national and local rates and modeled internal cohort rates to assess site-specific cancer risks by demographic and work history factors and several exposure indicators for AMD. RESULTS: For the 1925-2002 study period, we observed both deficit and excess overall mortality risks among the U.S. cohort for cancer sites implicated in experimental animal studies: brain and other central nervous system (SMR = 0.67, confidence interval [CI] = 0.40-1.05), thyroid gland (SMR = 1.38, CI = 0.28-4.02), testis and other male genital organs (SMR = 0.64, CI = 0.08-2.30); and for sites selected in earlier exploratory analyses of this cohort: respiratory system cancer (RSC) (SMR = 1.17, CI = 1.06-1.27), esophagus (SMR = 1.20, CI = 0.86-1.63), rectum (SMR = 1.25, CI = 0.84-1.78), pancreas (SMR = 0.94, CI = 0.70-1.22), and kidney (SMR = 1.01, CI = 0.66-1.46). Except for RSC, attributed earlier to muriatic acid exposure, none of the mortality excesses was statistically significant. In the Dutch cohort, we observed deficits in deaths for all sites of a priori interest. An updated analysis of our previous exploratory findings for pancreatic cancer in the U.S. cohort revealed much less evidence of a possible exposure-response relationship with AMD. CONCLUSION: AMD exposure at the levels present in our study sites was not associated with elevated cancer mortality risks. [ABSTRACT FROM AUTHOR]

We report the 1946-1992 mortality experience of 4008 females employed in any of 10 U.S. fiberglass manufacturing plants between 1945 and 1978 relative to external population rates. We also examine respiratory system cancer (RSC) mortality as a function of estimated exposure to respirable fibers (RFib), formaldehyde (FOR), silica, phenolics, urea, and other agents based on internal cohort comparisons. No statistically significantly elevated standardized mortality ratios were observed for all-cause mortality (930 deaths), any of the 25 nonmalignant causes considered, all malignant neoplasms (266 deaths), or any of the 27 malignant causes considered. Internal cohort comparisons revealed no significant positive associations between RSC mortality (53 cases) and exposure to RFib, FOR, or any of the other agents considered, although exposure levels were generally low. Some demographic subgroups appear to be at relatively increased risk of RSC. [ABSTRACT FROM AUTHOR]

Importance: Recent legislation facilitates veterans' ability to receive non-Veterans Affairs (VA) surgical care. Although veterans are predominantly male, the number of women receiving care within the VA has nearly doubled to 10% over the past decade and recent data comparing the surgical care of women in VA and non-VA care settings are lacking., Objective: To compare postoperative outcomes among women treated in VA hospitals vs private-sector hospitals., Design, Setting, and Participants: This coarsened exact-matched cohort study across 9 noncardiac specialties in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and American College of Surgeons National Surgical Quality Improvement Program (NSQIP) took place from January 1, 2016, to December 31, 2019. Multivariable Poisson models with robust standard errors were used to evaluate the association between VA vs private-sector care settings and 30-day mortality. Hospitals participating in American College of Surgeons NSQIP and VASQIP were included. Data analysis was performed in January 2023. Participants included female patients 18 years old or older., Exposures: Surgical care in VA or private-sector hospitals., Main Outcomes and Measures: Postoperative 30-day mortality and failure to rescue (FTR)., Results: Among 1 913 033 procedures analyzed, patients in VASQIP were younger (VASQIP: mean age, 49.8 [SD, 13.0] years; NSQIP: mean age, 55.9 [SD, 16.9] years; P < .001) and although most patients in both groups identified as White, there were significantly more Black women in VASQIP compared with NSQIP (29.6% vs 12.7%; P < .001). The mean risk analysis index score was lower in VASQIP (13.9 [SD, 6.4]) compared with NSQIP (16.3 [SD, 7.8]) (P < .001 for both). Patients in the VA were more likely to have a preoperative acute serious condition (2.4% vs 1.8%: P < .001), but cases in NSQIP were more frequently emergent (6.9% vs 2.6%; P < .001). The 30-day mortality, complications, and FTR were 0.2%, 3.2%, and 0.1% in VASQIP (n = 36 762 procedures) as compared with 0.8%, 5.0%, and 0.5% in NSQIP (n = 1 876 271 procedures), respectively (all P < .001). Among 1 763 540 matched women (n = 36 478 procedures in VASQIP; n = 1 727 062 procedures in NSQIP), these rates were 0.3%, 3.7%, and 0.2% in NSQIP and 0.1%, 3.4%, and 0.1% in VASQIP (all P < .01). Relative to private-sector care, VA surgical care was associated with a lower risk of death (adjusted risk ratio [aRR], 0.41; 95% CI, 0.23-0.76). This finding was robust among women undergoing gynecologic surgery, inpatient surgery, and low-physiologic stress procedures. VA surgical care was also associated with lower risk of FTR (aRR, 0.41; 95% CI, 0.18-0.92) for frail or Black women and inpatient and low-physiologic stress procedures., Conclusions and Relevance: Although women comprise the minority of veterans receiving care within the VA, in this study, VA surgical care for women was associated with half the risk of postoperative death and FTR. The VA appears better equipped to meet the unique surgical needs and risk profiles of veterans, regardless of sex and health policy decisions, including funding, should reflect these important outcome differences.

Introduction: The Risk Analysis Index (RAI) is a frailty assessment tool associated with adverse postoperative outcomes including 180 and 365-d mortality. However, the RAI has been criticized for only containing subjective inputs rather than including more objective components such as biomarkers., Methods: We conducted a retrospective cohort study to assess the benefit of adding common biomarkers to the RAI using the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database. RAI plus body mass index (BMI), creatinine, hematocrit, and albumin were evaluated as individual and composite variables on 180-d postoperative mortality., Results: Among 480,731 noncardiac cases in VASQIP from 2010 to 2014, 324,320 (67%) met our inclusion criteria. Frail patients (RAI ≥30) made up to 13.0% of the sample. RAI demonstrated strong discrimination for 180-d mortality (c = 0.839 [0.836-0.843]). Discrimination significantly improved with the addition of Hematocrit (c = 0.862 [0.859-0.865]) and albumin (c = 0.870 [0.866-0.873]), but not for body mass index (BMI) or creatinine. However, calibration plots demonstrate that the improvement was primarily at high RAI values where the model overpredicts observed mortality., Conclusions: While RAI's ability to predict the risk of 180-d postoperative mortality improves with the addition of certain biomarkers, this only observed in patients classified as very frail (RAI >49). Because very frail patients have significantly elevated observed and predicted mortality, the improved discrimination is likely of limited clinical utility for a frailty screening tool., (Published by Elsevier Inc.)

Background and Objectives: The Risk Analysis Index (RAI) accurately predicts adverse postoperative outcomes but the inclusion of cancer status in the RAI has raised two key concerns about its suitability for use in surgical oncology: (1) the potential over classification of cancer patients as frail, and (2) the potential overestimation of postoperative mortality for patients with surgically curable cancers., Methods: We performed a retrospective cohort analysis to assess the RAI's power to appropriately identify frailty and predict postoperative mortality in cancer patients. We assessed discrimination for mortality and calibration across five RAI models-the complete RAI and four variants that removed different cancer-related variables., Results: We found that the presence of disseminated cancer was a key variable driving the RAI's power to predict postoperative mortality. The model including only this variable [RAI (disseminated cancer)] was similar to the complete RAI in the overall sample (c = 0.842 vs. 0.840) and outperformed the complete RAI in the cancer subgroup (c = 0.736 vs 0.704, respectively, p < 0.0001, Max R 2  = 19.3% vs. 15.1%, respectively)., Conclusion: The RAI demonstrates somewhat less discrimination when applied exclusively to cancer patients, but remains a strong predictor of postoperative mortality, especially in the setting of disseminated cancer., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Importance: More than 75% of US adults with diabetes do not meet treatment goals. More effective support from family and friends ("supporters") may improve diabetes management and outcomes., Objective: To determine if the Caring Others Increasing Engagement in Patient Aligned Care Teams (CO-IMPACT) intervention improves patient activation, diabetes management, and outcomes compared with standard care., Design, Setting, and Participants: This randomized clinical trial was conducted from November 2016 to August 2019 among participants recruited from 2 Veterans Health Administration primary care sites. All patient participants were adults aged 30 to 70 years with diabetes who had hemoglobin A1c (HbA1c) levels greater than 8% of total hemoglobin (to convert to proportion of total hemoglobin, multiply by 0.01) or systolic blood pressure (SBP) higher than 150 mm Hg; each participating patient had an adult supporter. Of 1119 recruited, 239 patient-supporter dyads were enrolled between November 2016 and May 2018, randomized 1:1 to receive the CO-IMPACT intervention or standard care, and followed up for 12 to 15 months. Investigators and analysts were blinded to group assignment., Interventions: Patient-supporter dyads received a health coaching session focused on dyadic information sharing and positive support techniques, then 12 months of biweekly automated monitoring telephone calls to prompt dyadic actions to meet diabetes goals, coaching calls to help dyads prepare for primary care visits, and after-visit summaries. Standard-care dyads received general diabetes education materials only., Main Outcomes and Measures: Intent-to-treat analyses were conducted according to baseline dyad assignment. Primary prespecified outcomes were 12-month changes in Patient Activation Measure-13 (PAM-13) and UK Prospective Diabetes Study (UKPDS) 5-year diabetes-specific cardiac event risk scores. Secondary outcomes included 12-month changes in HbA1c levels, SBP, diabetes self-management behaviors, diabetes distress, diabetes management self-efficacy, and satisfaction with health system support for the involvement of family supporters. Changes in outcome measures between baseline and 12 months were analyzed using linear regression models., Results: A total of 239 dyads enrolled; among patient participants, the mean (SD) age was 60 (8.9) years, and 231 (96.7%) were male. The mean (SD) baseline HbA1c level was 8.5% (1.6%) and SBP was 140.2 mm Hg (18.4 mm Hg). A total of 168 patients (70.3%) lived with their enrolled supporter; 229 patients (95.8%) had complete 12-month outcome data. In intention-to-treat analyses vs standard care, CO-IMPACT patients had greater 12-month improvements in PAM-13 scores (intervention effect, 2.60 points; 95% CI, 0.02-5.18 points; P = .048) but nonsignificant differences in UKPDS 5-year cardiac risk (intervention effect, 1.01 points; 95% CI, -0.74 to 2.77 points; P = .26). Patients in the CO-IMPACT arm also had greater 12-month improvements in healthy eating (intervention effect, 0.71 d/wk; 95% CI, 0.20-1.22 d/wk; P = .007), diabetes self-efficacy (intervention effect, 0.40 points; 95% CI, 0.09-0.71 points; P = .01), and satisfaction with health system support for the family supporter participants' involvement (intervention effect, 0.28 points; 95% CI, 0.07-0.49 points; P = .009); however, the 2 arms had similar improvements in HbA1c levels and in other measures., Conclusions and Relevance: In this randomized clinical trial, the CO-IMPACT intervention successfully engaged patient-supporter dyads and led to improved patient activation and self-efficacy. Physiological outcomes improved similarly in both arms. More intensive direct coaching of supporters, or targeting patients with less preexisting support or fewer diabetes management resources, may have greater impact., Trial Registration: ClinicalTrials.gov Identifier: NCT02328326.

Objective: To discern whether there is evidence that individuals who sustained a traumatic brain injury (TBI) had the greater odds of preexisting health conditions and/or poorer health behaviors than matched controls without TBI., Setting: Brain Injury Inpatient Rehabilitation Unit at Mount Sinai Hospital. Midlife in the United States (MIDUS) control data were collected via random-digit-dialing phone survey., Participants: TBI cases were enrolled in the TBI Health Study and met at least 1 of the following 4 injury severity criteria: abnormal computed tomography scan; Glasgow Coma Scale score between 3 and 12; loss of consciousness greater than 30 minutes; or post-TBI amnesia longer than 24 hours. Sixty-two TBI cases and 171 matched MIDUS controls were included in the analyses; controls were excluded if they reported having a history of head injury., Design: Matched case-control study., Main Measures: Self-reported measures of depression symptoms, chronic pain, health status, alcohol use, smoking status, abuse of controlled substances, physical activity, physical health composite score, and behavioral health composite score., Results: Pre-index injury depression was nearly 4 times higher in TBI cases than in matched controls (OR= 3.98, 95% CI, 1.71-9.27; P = .001). We found no significant differences in the odds of self-reporting 3 or more medical health conditions in year prior to index injury (OR = 1.52; 95% CI, 0.82-2.81; P = .183) or reporting more risky health behaviors (OR = 1.48; 95% CI; 0.75-2.91; P = .254]) in individuals with TBI than in controls., Conclusion: These preliminary findings suggest that the odds of depression in the year prior to index injury far exceed those reported in matched controls. Further study in larger samples is required to better understand the relative odds of prior health problems in those who sustain a TBI, with a goal of elucidating the implications of preinjury health on post-TBI disease burden., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: US military veterans have disproportionately high rates of diabetes and diabetes-related morbidity in addition to being at risk of comorbid stress-related conditions. This study aimed to examine the effects of a technology-supported mindfulness intervention integrated into usual diabetes care and education on psychological and biobehavioral outcomes., Research Design and Methods: Veterans (N=132) with type 1 or 2 diabetes participated in this two-arm randomized controlled efficacy trial. The intervention arm received a one-session mindfulness intervention integrated into a pre-existing program of diabetes self-management education and support (DSMES) plus one booster session and 24 weeks of home practice supported by a mobile application. The control arm received one 3-hour comprehensive DSMES group session. The primary outcome was change in diabetes distress (DD). The secondary outcomes were diabetes self-care behaviors, diabetes self-efficacy, post-traumatic stress disorder (PTSD), depression, mindfulness, hemoglobin A1C (HbA1C), body weight, and blood pressure. Assessments were conducted at baseline, 12 weeks, and 24 weeks. Participant satisfaction and engagement in home practice were assessed in the intervention group at 12 and 24 weeks., Results: Intention-to-treat group by time analyses showed a statistically significant improvement in DD in both arms without significant intervention effect from baseline to 24 weeks. Examination of distal effects on DD between weeks 12 and 24 showed significantly greater improvement in the intervention arm. Improvement in DD was greater when baseline HbA1C was <8.5%. A significant intervention effect was also shown for general dietary behaviors. The secondary outcomes diabetes self-efficacy, PTSD, depression, and HbA1C significantly improved in both arms without significant intervention effects. Mindfulness and body weight were unchanged in either group., Conclusions: A technology-supported mindfulness intervention integrated with DSMES showed stronger distal effects on DD compared with DSMES control. Examination of longer-term outcomes, underlying mechanisms, and the feasibility of virtual delivery is warranted., Trial Registration Number: NCT02928952., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nonalcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the United States and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiologic data on iron overload without hemochromatosis in relation to HCC are sparse. This study aimed to examine the associations between serum biomarkers of iron and the risk of HCC in patients with NAFLD., Methods: We identified 18,569 patients with NAFLD using the University of Pittsburgh Medical Center electronic health records from 2004 through 2018. After an average 4.34 years of follow-up, 244 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of HCC incidence associated with elevated levels of iron biomarkers with adjustment for age, sex, race, body mass index, history of diabetes, and tobacco smoking., Results: The HRs (95% CIs) of HCC for clinically defined elevation of serum iron and transferrin saturation were 2.91 (1.34-6.30) and 2.02 (1.22-3.32), respectively, compared with their respective normal range. No statistically significant association was observed for total iron-binding capacity or serum ferritin with HCC risk., Conclusions: Elevated levels of serum iron and transferrin saturation were significantly associated with increased risk of HCC among patients with NAFLD without hemochromatosis or other major underlying causes of chronic liver diseases., Impact: Clinical surveillance of serum iron level may be a potential strategy to identify patients with NAFLD who are at high risk for HCC., (©2021 American Association for Cancer Research.)

Objectives: To assess what patient, family supporter, and call characteristics predicted whether patients completed automated and coach-provided calls in a telehealth diabetes intervention., Study Design: A total of 123 adults with type 2 diabetes and high glycated hemoglobin A1c (HbA1c) or blood pressure, enrolled with a family supporter, received automated interactive voice response (IVR) and coach-provided visit preparation calls over 12 months., Methods: Data from baseline surveys and diabetes-related clinical information from patient medical records were entered into multilevel, multivariate regression models of associations between participant and call characteristics with call completion., Results: A total of 76.3% of 2784 IVR calls and 75.8% of 367 visit preparation calls were completed. For IVR calls, patients with recent call-triggered provider alerts had higher odds of call completion (adjusted odds ratio [AOR], 3.5; 95% CI, 2.2-5.5); those with depressive symptoms (AOR, 0.4; 95% CI, 0.2-0.9), higher HbA1c (AOR, 0.8; 95% CI, 0.6-0.99), and more months in the study (AOR, 0.9; 95% CI, 0.87-0.94 per month) had lower odds. For visit preparation calls, higher patient activation scores predicted higher call completion (AOR, 1.4; 95% CI, 1.1-1.9); patient college education predicted less call completion (AOR, 0.3; 95% CI, 0.2-0.6). Supporter help taking medications predicted less completion of both call types. Patient age did not predict call completion., Conclusions: Patients of all ages completed telehealth calls at a high rate. Automated IVR calls were completed more often when urgent issues were identified to patients' providers, but less often if patients had high HbA1c or depression. Visit preparation call content should be tailored to patient education level. Family help with medications may identify patients needing additional support to engage with telehealth.

Objective: To evaluate race and gender variations in complementary and alternative medicine (CAM) use for knee osteoarthritis (OA) (unadjusted and adjusted for demographic and clinical factors)., Methods: A secondary analysis of cross-sectional data was conducted. The sample included Veterans Affairs patients 50 years of age or older with symptomatic knee OA. Current use of various CAM therapies was assessed at baseline. Logistic regression models were used to compare race and gender differences in the use of specific CAMs., Results: The sample included 517 participants (52.2% identified as African American [AA]; 27.1% identified as female). After adjusting for demographic and clinical factors, AA participants, compared with white participants, were less likely to use joint supplements (odds ratio [OR]: 0.53; 95% confidence interval [CI], 0.31-0.90]); yoga, tai chi, or pilates (OR: 0.39; 95% CI: 0.19-0.77); and chiropractic care (OR: 0.51; 95% CI: 0.26-1.00). However, they were more likely to participate in spiritual activities (OR: 2.02; 95% CI: 1.39-2.94). Women, compared with men, were more likely to use herbs (OR: 2.42; 95% CI: 1.41-4.14); yoga, tai chi, or pilates (OR: 2.09; 95% CI: 1.04-4.19); acupuncture, acupressure, or massage (OR: 2.45; 95% CI: 1.28-4.67); and spiritual activities (OR: 1.68; 95% CI: 1.09-2.60). The interactive effects of race and gender were significant in the use of herbs (P = 0.008); yoga, tai chi, or pilates (P = 0.011); acupuncture, acupressure or massage (P = 0.038); and spiritual activities (P < 0.001)., Conclusion: There are race and gender differences in the use of various CAMs for OA. As benefits and limitations of CAM therapies vary, clinicians must be aware of these differences., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination., Methods: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection., Results: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ≥5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2)., Conclusion: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: This study examines the differences in suicide, homicide, and all-cause mortality between transgender and cisgender Veterans Health Administration (VHA) patients. Methods: VHA electronic medical record data from October 1, 1999 to December 31, 2016 were used to create a sample of transgender and cisgender patients ( n  = 32,441). Cox proportional hazard regression was used to evaluate differences in survival time (date of birth to death date/study end). Death data were from the National Death Index. Results: Transgender patients had more than twofold greater hazard of suicide than cisgender patients (adjusted hazard ratio [aHR] = 2.77, 95% confidence interval [CI] = 1.88-4.09), especially among younger (18-39 years) (aHR = 3.35, 95% CI = 1.30-8.60) and older (≥65 years) patients (aHR = 9.48, 95% CI = 3.88-23.19). Alternatively, transgender patients had an overall lower hazard of all-cause mortality (aHR = 0.90, 95% CI = 0.84-0.97) compared with cisgender patients, which was driven by patients 40-64 years old (aHR = 0.78, 95% CI = 0.72-0.86) and reversed by those 65 years and older (aHR = 1.17, 95% CI = 1.03-1.33). Conclusion: Transgender patients' hazard of suicide mortality was significantly greater than that of cisgender VHA patients.

The goal of this study was to compare a brief behavioral treatment for insomnia (BBTI), which has fewer sessions (4), shorter duration (<30-45 minutes), and delivers treatment in-person plus phone calls to cognitive behavioral therapy for insomnia (CBTI), which has 5 in-person sessions. The hypothesis was BBTI would be noninferior to CBTI. The Reliable Change Index was used to establish a noninferiority margin (NIM) of 3.43, representing the maximum allowable difference between groups on the pre-post Insomnia Severity Index change (ΔISI). Sixty-three veterans with chronic insomnia were randomized to either BBTI or CBTI and veterans in both groups had significant reductions of their insomnia severity per the ISI and improved their sleep onset latency, total wake time, sleep efficiency, and sleep quality per sleep diaries. While CBTI had a larger pre-post ΔISI, this was not significantly different than ΔISI BBTI and was less than the NIM. However, the 95% confidence interval of the between group pre-post ΔISI extended beyond the NIM, and thus BBTI was inconclusively noninferior to CBTI. Limitations, such as small sample size and high rate of dropout, indicate further study is needed to compare brief, alternative yet complementary behavioral insomnia interventions to CBTI. Still, evidence-based brief and flexible treatment options will help to further enhance access to care for veterans with chronic insomnia, especially in non-mental-health settings like primary care., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To describe clinical findings and survival times for dogs with functional thyroid tumors treated with surgery alone and investigate potential prognostic factors for outcome in these patients., Animals: 27 client-owned dogs., Procedures: Medical records of 9 institutions were reviewed to identify dogs with hyperthyroidism secondary to thyroid neoplasia that were treated with surgery alone between 2005 and 2015. Data collected included signalment, hematologic and physical examination findings, tumor staging results, time from diagnosis to treatment, surgical procedure performed, histologic findings, evidence of recurrence or metastatic disease, and date of death or last follow-up. Median survival time and 1-, 2-, and 3-year survival rates were assessed by Kaplan-Meier analysis. Associations between variables of interest and the outcome of death were assessed with Cox proportional hazards models., Results: Dogs from 8 institutions met inclusion criteria. Median age at diagnosis was 10 years (range, 8 to 13 years). Golden Retrievers and Labrador Retrievers were commonly represented (5 dogs each). Polyuria with polydipsia (15/27 [56%]) and weight loss (12 [44%]) were the most common clinical signs; 2 dogs without clinical signs had hyperthyroidism identified by routine hematologic analysis. One dog had metastatic disease at the time of diagnosis. Most tumors (23/27 [85%]) were malignant. Estimated median survival time was 1,072 days. No significant prognostic factors were identified., Conclusions and Clinical Relevance: Dogs with resectable functional thyroid tumors had a good prognosis with surgical excision alone. Survival times for these dogs were similar to those in previous studies that included dogs with nonfunctional thyroid tumors.

Objective: This prospective, longitudinal study explored the impact of a continuing education class on librarians' knowledge levels about and professional involvement with systematic reviews. Barriers to systematic review participation and the presence of formal systematic review services in libraries were also measured., Methods: Participants completed web-based surveys at three points in time: pre-class, post-class, and six-months' follow-up. Descriptive statistics were calculated for demographics and survey questions. Linear mixed effects models assessed knowledge score changes over time., Results: Of 160 class attendees, 140 (88%) completed the pre-class survey. Of those 140, 123 (88%) completed the post-class survey, and 103 (74%) completed the follow-up survey. There was a significant increase ( p <0.00001) from pre-class to post-class in knowledge test scores, and this increase was maintained at follow-up. At post-class, 69% or more of participants intended to promote peer review of searches, seek peer review of their searches, search for grey literature, read or follow published guidelines on conduct and documentation of systematic reviews, and ask for authorship on a systematic review. Among librarians who completed a systematic review between post-class and follow-up, 73% consulted published guidelines, 52% searched grey literature, 48% sought peer review, 57% asked for authorship, and 70% received authorship., Conclusions: Attendance at this continuing education class was associated with positive changes in knowledge about systematic reviews and in librarians' systematic review-related professional practices. This suggests that in-depth professional development classes can help librarians develop skills that are needed to meet library patrons' changing service needs., (Copyright: © 2020, Authors.)

Objective: To describe the planning of a modified cranial closing wedge ostectomy (mCCWO) and determine the accuracy of execution without intraoperative jigs or alignment guides., Study Design: Retrospective study., Animals: Twenty-five client-owned dogs (32 stifles) with cranial cruciate ligament disease., Methods: Medical records of dogs treated with mCCWO between July 2014 and December 2016 were reviewed. Preoperative, postoperative, and 8-week-recheck radiographs were reviewed to measure changes in the conformation of the proximal tibia. The accuracy of execution was assessed by comparing planned and actual postoperative tibial plateau angle (TPA) and the lengths of bone contact along osteotomy lines. Radiographic healing and clinical outcome were subjectively evaluated 8 weeks after surgery., Results: Preoperative planning of mCCWO decreased the cranial wedge length by a mean of 23% compared with the traditional CCWO planning. Mean TPA decreased from 40.69 ° (range 28-63) to 6.94 ° (range 2-20) after surgery (P < .001). Mean tibial length decreased by 0.5 mm (±0.16, P = .003), from 138 mm (range 65-267) to 137.5 mm (range 65-265) after mCCWO. The tibial long axis (TLA) shifted by a mean of 3.47 ° (range 0-10). Planned and actual postoperative TPA differed by -0.66 ° (±0.47, P = .034). The proximal and distal apposing osteotomies differed in length by 1.81 mm (±0.35). No bone healing complications or implant failures were diagnosed, and all dogs returned to subjectively satisfactory function by 8 weeks after surgery., Conclusion: The preoperative planning and methods of execution of the mCCWO resulted in differences in target TPA and postoperative TPA, differences in lengths of proximal and distal osteotomies, and tibial shortening that did not appear clinically significant in this study., Clinical Significance: mCCWO can be planned and accurately executed without consideration of TLA shift or the intraoperative use of alignment guides or jigs., (© 2018 The American College of Veterinary Surgeons.)

Purpose of the Study: In a number of states, physicians are mandated by state law to report at-risk drivers to licensing authorities. Often these patients are older adult drivers who may exhibit unsafe driving behaviors, have functional/cognitive impairments, or are diagnosed with conditions such as Alzheimer's disease and/or seizure disorders. The hypothesis that mandatory physician reporting laws reduce the rate of crash-related hospitalizations among older adult drivers was tested., Design and Methods: Using retrospective data (2004-2009), this study identified 176,066 older driver crash-related hospitalizations, from the State Inpatient Databases. Three age-specific negative binomial generalized estimating equation models were used to estimate the effect of physician reporting laws on state's incidence rate of crash-related hospitalizations among older drivers., Results: No evidence was found for an independent association between mandatory physician reporting laws and a lower crash hospitalization rate among any of the age groups examined. The main predictor of interest, mandatory physician reporting, failed to explain any significant variation in crash hospitalization rates, when adjusting for other state-specific laws and characteristics. Vision testing at in-person license renewal was a significant predictor of lower crash hospitalization rate, ranging from incidence rate ratio of 0.77 (95% confidence interval 0.62-0.94) among 60- to 64-year olds to 0.83 (95% confidence interval 0.67-0.97) among 80- to 84-year olds., Implications: Physician reporting laws and age-based licensing requirements are often at odds with older driver's need to maintain independence. This study examines this balance and finds no evidence of the benefits of mandatory physician reporting requirements on driver crash hospitalizations, suggesting that physician mandates do not yet yield significant older driver safety benefits, possibly to the detriment of older driver's well-being and independence.

Objective: To determine the effect of physician reporting laws and state licensing requirements on crash hospitalizations among drivers with dementia., Methods: A study of drivers hospitalized because of vehicle crashes, identified from the State Inpatient Databases of the Agency for Healthcare Research and Quality. Multivariable logistic regression was used to examine the effect of mandatory physician reporting of at-risk drivers and state licensing requirement on the prevalence of dementia among hospitalized drivers., Results: Physician reporting laws, mandated or legally protected, were not associated with a lower likelihood of dementia among crash hospitalized drivers. Hospitalized drivers aged 60 to 69 years in states with in-person renewal laws were 37% to 38% less likely to have dementia than drivers in other states and 23% to 28% less likely in states with vision testing at in-person renewal. Road testing was associated with lower dementia prevalence among hospitalized drivers aged 80 years and older., Conclusion: Vision testing at in-person renewal and in-person renewal requirements were significantly related with a lower prevalence of dementia in hospitalized older adults among drivers aged 60 to 69 years. Road testing was significantly associated with a lower proportion of dementia among hospitalized drivers aged 80 years and older. Mandatory physician driver reporting laws lacked any independent association with prevalence of dementia among hospitalized drivers., (© 2018 American Academy of Neurology.)

Background: Chronic insomnia is among the most reported complaints of Veterans and military personnel referred for mental health services. It is highly comorbid with medical and psychiatric disorders, and is associated with significantly increased healthcare utilization and costs. Evidence-based psychotherapy, namely Cognitive Behavioral Therapy for Insomnia (CBTI), is an effective treatment and recommended over prescription sleep medications. While CBTI is part of a nationwide rollout in the Veterans Health Administration to train hundreds of providers, access to treatment is still limited for many Veterans due to limited treatment availability, low patient and provider knowledge about treatment options, and Veteran barriers such as distance and travel, work schedules, and childcare. Uptake of a briefer, more primary-care-friendly treatment into routine clinical care in Veterans Affairs (VA) primary care settings, where insomnia is typically first recognized and diagnosed, may effectively and efficiently increase access to effective insomnia interventions and help decrease the risks and burdens related to chronic insomnia., Methods: This hybrid type I trial is composed of two aims. The first preliminarily tests the clinical non-inferiority of Brief Behavioral Treatment for Insomnia (BBTI) versus the current "gold standard" treatment, CBTI. The second is a qualitative needs assessment, guided by the Consolidated Framework for Implementation Research (CFIR), to identify potential factors that may affect successful implementation and integration of behavioral treatments for insomnia in the primary care setting. To identify potential implementation factors, individual interviews are conducted with the Veterans who participate in the clinical trial, as well as VA primary care providers and nursing staff., Discussion: It is increasingly important to better understand barriers to, and facilitators of, implementing insomnia interventions in order to ensure that Veterans have the best access to care. Furthermore, it is important to evaluate the potential for new avenues of treatment delivery, like BBTI in the primary care setting, which can benefit Veterans who may not have adequate access to specialty mental health providers trained in CBTI., Trial Registration: ClinicalTrials.gov, ID: NCT02724800 . Registered on 31 March 2016.

Modeling of correlated biomarkers jointly has been shown to improve the efficiency of parameter estimates, leading to better clinical decisions. In this paper, we employ a joint modeling approach to a unique diabetes dataset, where blood glucose (continuous) and urine glucose (ordinal) measures of disease severity for diabetes are known to be correlated. The postulated joint model assumes that the outcomes are from distributions that are in the exponential family and hence modeled as multivariate generalized linear mixed effects model associated through correlated and/or shared random effects. The Markov chain Monte Carlo Bayesian approach is used to approximate posterior distribution and draw inference on the parameters. This proposed methodology provides a flexible framework to account for the hierarchical structure of the highly unbalanced data as well as the association between the 2 outcomes. The results indicate improved efficiency of parameter estimates when blood glucose and urine glucose are modeled jointly. Moreover, the simulation studies show that estimates obtained from the joint model are consistently less biased and more efficient than those in the separate models., (Copyright © 2017 John Wiley & Sons, Ltd.)

Increased ectopic adipose tissue infiltration in skeletal muscle is associated with insulin resistance and diabetes mellitus. We evaluated whether change in skeletal muscle adiposity predicts subsequent development of hypertension in men of African ancestry, a population sample understudied in previous studies. In the Tobago Health Study, a prospective longitudinal study among men of African ancestry (age range 40-91 years), calf intermuscular adipose tissue, and skeletal muscle attenuation were measured with computed tomography. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg, or receiving antihypertensive medications. Logistic regression was performed with adjustment for age, insulin resistance, baseline and 6-year change in body mass index, baseline and 6-year change in waist circumference, and other potential confounding factors. Among 746 normotensive men at baseline, 321 (43%) developed hypertension during the mean 6.2 years of follow-up. Decreased skeletal muscle attenuation was associated with newly developed hypertension after adjustment for baseline and 6-year change of body mass index (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]) or baseline and 6-year change of waist circumference (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]). No association was observed between increased intermuscular adipose tissue and hypertension. Our novel findings show that decreased muscle attenuation is associated with newly developed hypertension among men of African ancestry, independent of general and central adiposity and insulin resistance. Further studies are needed to adjust for inflammation, visceral and other ectopic adipose tissue depots, and to confirm our findings in other population samples., (© 2017 American Heart Association, Inc.)

Parametric mixed-effects models are useful in longitudinal data analysis when the sampling frequencies of a response variable and the associated covariates are the same. We propose a three-step estimation procedure using local polynomial smoothing and demonstrate with data where the variables to be assessed are repeatedly sampled with different frequencies within the same time frame. We first insert pseudo data for the less frequently sampled variable based on the observed measurements to create a new dataset. Then standard simple linear regressions are fitted at each time point to obtain raw estimates of the association between dependent and independent variables. Last, local polynomial smoothing is applied to smooth the raw estimates. Rather than use a kernel function to assign weights, only analytical weights that reflect the importance of each raw estimate are used. The standard errors of the raw estimates and the distance between the pseudo data and the observed data are considered as the measure of the importance of the raw estimates. We applied the proposed method to a weight loss clinical trial, and it efficiently estimated the correlation between the inconsistently sampled longitudinal data. Our approach was also evaluated via simulations. The results showed that the proposed method works better when the residual variances of the standard linear regressions are small and the within-subjects correlations are high. Also, using analytic weights instead of kernel function during local polynomial smoothing is important when raw estimates have extreme values, or the association between the dependent and independent variable is nonlinear. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations., Methods: in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy., Results: one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models., Conclusions: our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease., Methods: Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34)., Results: Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT., Conclusions: Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids.

Background: Various hospital accreditation and quality assurance entities in the United States have approved and endorsed performance measures promoting alcohol brief intervention (BI) for hospitalized individuals who screen positive for unhealthy alcohol use, the spectrum of use ranging from hazardous use to alcohol use disorders. These performance measures have been controversial due to the limited and equivocal evidence for the efficacy of BI among hospitalized individuals. The few BI trials conducted with hospital inpatients vary widely in methodological quality. While the majority of these studies indicate limited to no effects of BI in this population, none have been designed to account for the most pervasive methodological issue in BI studies presumed to drive study findings towards the null: assessment reactivity (AR)., Methods/design: This is a three-arm, single-site, randomized controlled trial of BI for hospitalized patients at a large academic medical center affiliated with the U.S. Department of Veterans Affairs who use alcohol at hazardous levels but do not have an alcohol use disorder. Participants are randomized to one of three study conditions. Study Arm 1 receives a three-part alcohol BI. Study Arm 2 receives attention control. To account for potential AR, Study Arm 3 receives AC with limited assessment. Primary outcomes will include the number of standard drinks/week and binge drinking episodes reported in the 30-day period prior to a final measurement visit obtained 6 months after hospital discharge. Additional outcomes will include readiness to change drinking behavior and number of adverse consequences of alcohol use. To assess differences in primary outcomes across the three arms, we will use mixed-effects regression models that account for a patient's repeated measures over the timepoints and clustering within medical units. Intervention implementation will be assessed by: a) review of intervention audio recordings to characterize barriers to intervention fidelity; and b) feasibility of participant recruitment, enrollment, and follow-up., Discussion: The results of this methodologically rigorous trial will provide greater justification for or against the use of BI performance measures in the inpatient setting and inform organizational responses to BI-related hospital accreditation and performance measures., Trial Registration: NCT01602172.

The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes.

Objectives: To evaluate the extent to which lung cancer mortality risk estimates in relation to acrylonitrile (AN) exposure may have been confounded by smoking in the presence of misclassified smoking data., Methods: Subjects were 992 white men employed for three or more months between 1960 and 1996 at a chemical plant in Lima, Ohio. We used Monte Carlo-based sensitivity analysis to address possible confounding by smoking., Results: In Monte Carlo simulations that accounted for the relationship between smoking and AN exposure, mean relative risks for lung cancer mortality in relation to AN exposure decreased and we observed somewhat less evidence of an exposure-response relationship., Conclusions: Our simulations suggest that the relationship between AN exposure and lung cancer mortality was positively confounded by smoking in the original Lima cohort study.

Objective: To determine the impact of coal mining, measured as the number of coal mining-related facilities nearby one's residence or employment in an occupation directly related to coal mining, on self-rated health in Appalachia., Methods: Unadjusted and adjusted ordinal logistic regression models calculated odds ratio estimates and associated 95% confidence intervals for the probability of having an excellent self-rated health response versus another response. Covariates considered in the analyses included number of coal mining-related facilities nearby one's residence and employment in an occupation directly related to coal mining, as well as potential confounders age, sex, BMI, smoking status, income, and education., Results: The number of coal mining facilities near the respondent's residence was not a statistically significant predictor of self-rated health. Employment in a coal-related occupation was a statistically significant predictor of self-rated health univariably; however, after adjusting for potential confounders, it was no longer a significant predictor., Conclusions: Self-rated health does not seem to be associated with residential proximity to coal mining facilities or employment in the coal industry. Future research should consider additional measures for the impact of coal mining.

Objective: To determine whether mortality disparities in Appalachia are due to coal mining or other factors., Methods: Unadjusted and covariate adjusted rate ratio models calculated total, all external, and all cancer mortality rates from 1960 to 2009 for cumulative total, surface, and underground coal production in coal-mining counties compared with non-coal-mining counties., Results: No coal-related statistically significant elevations in total or all external mortality were found. Control for covariates attenuated rate ratios for all levels of coal mining. All forms of coal were statistically significant in the adjusted rate ratio models for all cancer mortality, with 4% to 6% excesses in the highest quartiles of production., Conclusions: Total and all external mortalities do not seem to be related to coal production in Appalachia, but all cancer mortality should be further examined. Additional causes of death should also be considered.

β-Chloroprene (2-chloro-1,3-butadiene, CD) is used in the manufacture of polychloroprene rubber. Chronic inhalation studies have demonstrated that CD is carcinogenic in B6C3F1 mice and Fischer 344 rats. However, epidemiological studies do not provide compelling evidence for an increased risk of mortality from total cancers of the lung. Differences between the responses observed in animals and humans may be related to differences in toxicokinetics, the metabolism and detoxification of potentially active metabolites, as well as species differences in sensitivity. The purpose of this study was to develop and apply a novel method that combines the results from available physiologically based kinetic (PBK) models for chloroprene with a statistical maximum likelihood approach to test commonality of low-dose risk across species. This method allows for the combined evaluation of human and animal cancer study results to evaluate the difference between predicted risks using both external and internal dose metrics. The method applied to mouse and human CD data supports the hypothesis that a PBK-based metric reconciles the differences in mouse and human low-dose risk estimates and further suggests that, after PBK metric exposure adjustment, humans are equally or less sensitive than mice to low levels of CD exposure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Studies have suggested an increase in maternal morbidity and mortality due to cardiovascular diseases in women with a prior low-birth-weight (LBW, <2,500 grams) delivery. This study evaluated blood pressure and hypertension in women who reported a prior preterm or small-for-gestational-age (SGA) LBW delivery in the National Health and Nutrition Examination Survey 1999-2006 (n = 6,307). This study also aimed to explore if race/ethnicity, menopause status, and years since last pregnancy modified the above associations. A total of 3,239 white, 1,350 black, and 1,718 Hispanics were assessed. Linear regression models were used to evaluate blood pressure by birth characteristics (preterm-LBW, SGA-LBW, and birthweight ≥2,500). Logistic regression models estimated the odds ratios (OR) of hypertension among women who reported a preterm-LBW or SGA-LBW delivery compared with women who reported an infant with birthweight ≥2,500 at delivery. Overall, there was a positive association between a preterm-LBW delivery and hypertension (adjusted OR = 1.39, 95% confidence interval (CI) 1.02-1.90). Prior SGA-LBW also increased the odds of hypertension, but the estimate did not reach statistical significance (adjusted OR = 1.21, 95% CI 0.76-1.92). Race/ethnicity modified the above associations. Only black women had increased risk of hypertension following SGA-LBW delivery (adjusted OR = 2.09, 95% CI 1.12-3.90). Black women were at marginally increased risk of hypertension after delivery of a preterm-LBW (adjusted OR = 1.49, 95% CI 0.93-2.38). Whites and Hispanics had increased, but not statistically significant, risk of hypertension after a preterm-LBW (whites: adjusted OR = 1.39, 95% CI 0.92-2.10; Hispanics: adjusted OR = 1.22, 95% CI 0.62-2.38). Stratified analysis indicated that the associations were stronger among women who were premenopausal and whose last pregnancy were more recent. The current study suggests that in a representative United States population, women with a history of preterm- or SGA-LBW deliveries have increased odds of hypertension and this risk appears to be higher for black women and younger women.

Objective: Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression., Method: Youth (51% female and 49% male; age 9-17 years, mean age 14.3 years) with depression and Crohn's disease (n = 161) or ulcerative colitis (n = 56) were randomly assigned to a 3-month course of CBT or SNDT. The primary outcome was comparative reduction in depressive symptom severity; secondary outcomes were depression remission, increase in depression response, and improved health-related adjustment and IBD activity., Results: A total of 178 participants (82%) completed the 3-month intervention. Both psychotherapies resulted in significant reductions in total Children's Depression Rating Scale Revised score (37.3% for CBT and 31.9% for SNDT), but the difference between the 2 treatments was not significant (p = .16). There were large pre-post effect sizes for each treatment (d = 1.31 for CBT and d = 1.30 for SNDT). More than 65% of youth had a complete remission of depression at 3 months, with no difference between CBT and SNDT (67.8% and 63.2%, respectively). Compared to SNDT, CBT was associated with a greater reduction in IBD activity (p = .04) but no greater improvement on the Clinical Global Assessment Scale (p = .06) and health-related quality of life (IMPACT-III scale) (p = .07)., Conclusion: This is the first randomized controlled study to suggest improvements in depression severity, global functioning, quality of life, and disease activity in a physically ill pediatric cohort treated with psychotherapy. Clinical trial registration information-Reducing Depressive Symptoms in Physically Ill Youth; http://clinical trials.gov; NCT00534911., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Despite lack of consensus criteria, biliary dyskinesia (BD) is an increasingly accepted pediatric diagnosis., Aims: We compared patient characteristics, outcomes, and resource utilization (before and after surgery) between children with BD and symptomatic cholecystolithiasis (LITH)., Methods: Data from the electronic medical record were abstracted for children diagnosed with BD or LITH between December 1, 2002, and November 30, 2012, at Children's Hospital of Pittsburgh., Results: Four hundred and ten patients were identified (BD: 213 patients, LITH: 197 patients). Patients with BD had significantly lower BMI, longer symptom duration, more dyspeptic symptoms, and were more likely to present with other symptoms. Forty-one patients (13.8%) with BD underwent cholecystectomy despite a normal gallbladder ejection fraction (GB-EF). In 32 of these, sincalide triggered pain compared to 75 of the 155 patients with low GB-EF. After surgery, patients with BD more commonly visited gastroenterology clinics and had more GI-related hospitalizations, while emergency room visits decreased in both groups. Only the nature of biliary disease independently predicted continuing pain after surgery, which in turn was the best predictor for higher resource utilization after cholecystectomy., Conclusions: A large percentage of children with BD did not meet the adult diagnostic standards. Compared to those with LITH, children with BD have more widespread symptoms and continue to use more clinical resources after surgery. These findings suggest that despite its benign prognosis, BD is increasingly treated like other potentially acute gallbladder diseases, although it has the typical phenotype of FGIDs and should be treated using approaches used in such disorders.

Background & Aims: Telephone communication is common between healthcare providers and patients with inflammatory bowel disease (IBD). We analyzed telephone activity at an IBD care center to identify disease and patient characteristics associated with high levels of telephone activity and determine if call volume could identify individuals at risk for future visits to the emergency department (ED) or hospitalization., Methods: We performed a prospective observational study in which we categorized telephone calls received by nursing staff over 2 years at a tertiary care IBD clinic (2475 patients in 2009 and 3118 in 2010). We analyzed data on 21,979 ingoing and outgoing calls in 2009 and 32,667 calls in 2010 and assessed associations between clinical factors and logged telephone encounters, and between patterns of telephone encounters and future visits to the ED or hospitalization., Results: Telephone encounters occurred twice as frequently as office visits; 15% of the patients generated >10 telephone encounters per year and were responsible for half of all telephone encounters. A higher percentage of these high telephone encounter (HTE) patients were female, had Crohn's disease, received steroid treatment, had increased levels of C-reactive protein and rates of erythrocyte sedimentation, had psychiatric comorbidities, and had chronic abdominal pain than patients with lower telephone encounters. The HTE patients were also more frequently seen in the ED or hospitalized over the same time period and in subsequent years. Forty-two percent of patients with >8 telephone encounters within 30 days were seen in the ED or hospitalized within the subsequent 12 months., Conclusions: Based on an analysis of telephone records at an IBD clinic, 15% of patients account for half of all calls. These HTE patients are a heterogeneous group with refractory disease who are likely to visit the ED or be hospitalized., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: The association between inflammatory bowel disease (IBD) and depression provides a unique opportunity to understand the relation between systemic inflammation and depressive symptom profiles., Methods: Youth (n = 226) ages 9 to 17 years with comorbid IBD and depression underwent psychiatric assessment and evaluation of IBD activity. Latent profile analysis (LPA) identified depressive subgroups based on similar responses to the Children's Depression Rating Scale-Revised. Demographic factors, depression severity, anxiety, IBD activity, inflammatory markers, IBD-related medications, and illness perception were evaluated as predictors of profile membership., Results: Mean age was 14.3 years; 75% had Crohn disease; 31% were taking systemic corticosteroids. Mean depressive severity was moderate, whereas IBD activity, which reflects inflammation, was mild. LPA identified 3 subgroups: Profile-1 (mild, 75%) had diverse low-grade depressive symptoms and highest quality of life; Profile-2 (somatic, 19%) had severe fatigue, appetite change, anhedonia, decreased motor activity, and depressed mood with concurrent high-dose steroid therapy and the highest IBD activity; and Profile-3 (cognitive, 6%) had the highest rates of self-reported depressive symptoms, ostomy placements, and anxiety with IBD symptoms in the relative absence of inflammation., Conclusions: Evidence was found for 3 depression profiles in youth with IBD and depression. Our analyses determined that patients with predominantly somatic or cognitive symptoms of depression comprised 25% of our cohort. These findings may be used to design subgroup-specific interventions for depression in adolescents with IBD and other physical illnesses associated with systemic inflammation.

Objective: The aim of the study was to determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn disease (CD)., Methods: A total of 550 (n = 550) youth ages 9 to 17 years with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized controlled trial. Out of the 550, 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children's Depression Inventory (CDI). A child or parent CDI score ≥  12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn's Disease Activity Index (PCDAI) were collected as the potential predictors of depression. Univariate regression models were constructed to determine the relations among predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relation between infliximab use and depression while controlling for other predictors of depression., Results: Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (P < 0.01) and negatively associated with socioeconomic status (SES) (P < 0.001). In multivariate models, PCDAI and SES were the strongest predictors of depression., Conclusions: Disease activity and SES are significant predictors of depression in youth with Crohn disease.

Unlabelled: Inducing temporary positive states reduces pain and increases pain tolerance in laboratory studies. We tested whether completing positive activities in one's daily life produces long-term reductions in self-reported bodily pain in a randomized controlled trial of an online positive activities intervention. Participants recruited via the Web were randomly assigned to complete 0, 2, 4, or 6 positive activities administered online over a 6-week period. Follow-up assessments were collected at the end of 6 weeks and at 1, 3, and 6 months postintervention. We used linear mixed effects models to examine whether the intervention reduced pain over time among those who had a score <67 on the bodily pain subscale of the Short Form-36 at baseline (N = 417; pain scores range from 0 to 100; higher scores indicate less pain). Mean pain scores improved from baseline to 6 months in the 2-activity (55.7 to 67.4), 4-activity (54.2 to 71.0), and 6-activity (50.9 to 67.9) groups. Improvements were significantly greater (P < .05) in the 4-activity and 6-activity groups than in the 0-activity control group (54.1 to 62.2) in unadjusted and adjusted models. This study suggests that positive activities administered online can reduce bodily pain in adults with at least mild to moderate baseline pain., Perspective: This study demonstrates that teaching people simple positive activities can decrease reported levels of bodily pain; moreover, these activities can be administered over the internet, a potential avenue for broadly disseminating health interventions at relatively low costs and with high sustainability., (Published by Elsevier Inc.)

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal-Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0-300)] relative to HPV-positive HNSCC [7.5 (0-200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = -0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.

Introduction: Passive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain., Methods: We conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression., Results: CPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01-1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80-1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at non-oropharyngeal sites (OR, 2.02; 95% CI, 1.01-4.06, N=52 cases vs. OR, 1.04; 95% CI, 0.68-1.60, N=132 cases; P-for-heterogeneity=0.08)., Conclusions: Data from this large US-based case control study suggest a role for CPSE in HNSCC etiology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC)., Methods: OOSCC cases (N=159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan-Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups., Results: Kaplan-Meier analyses showed N-acteyltransferase-2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P=0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10-0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54-2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31-1.59) (P-for-NAT2/treatment-interaction=0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5-year disease-specific survival relative to reduced activity GSTP1 (P=0.04) but this association was not modified by treatment., Conclusions: Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To reconstruct agent-specific occupational exposures for a cohort of jet engine manufacturing workers for use in an epidemiological mortality study., Methods: Potential chemical and physical exposures at eight jet engine manufacturing and overhaul/repair plants were evaluated for the period 1952 to 2001. Eleven agents were selected for detailed examination, and a job-exposure matrix was constructed., Results: Quantitative exposure estimates were generated for metalworking fluids, nickel, cobalt, chromium, solvents, and incomplete combustion aerosol from metalworking fluids. Qualitative exposure estimates were assigned for ionizing radiation, electromagnetic fields, polychlorinated biphenyls, and lead-cadmium. All exposures showed decreasing trends over the study period., Conclusions: The quantitative exposure levels generated in this study were lower than early contemporaneous professional practice recommendations and were similar to or lower than published data from other industries.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures., Methods: Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents., Results: In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven., Conclusions: If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

Objective: To evaluate mortality rates among a cohort of jet engine manufacturing workers., Methods: Subjects were 222,123 workers employed from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,317 deaths. We computed standardized mortality ratios and modeled internal cohort rates., Results: Mortality excesses reported initially no longer met the criteria for further investigation. We found two chronic obstructive pulmonary disease-related mortality excesses that met the criteria in two of eight study plants., Conclusions: At the total cohort level, chronic obstructive pulmonary disease-related categories were not related to any factors or occupational exposures considered. A full evaluation of these excesses was limited by lack of data on smoking history. Occupational exposures received outside of work or uncontrolled positive confounding by smoking cannot be ruled out as reasons for these excesses.

Objective: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed., Methods: Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases., Results: In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk., Conclusions: If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.