Pain interference and health-related quality of life in caregivers of service members and veterans with traumatic brain injury and mental health comorbidity.

PURPOSE: To examine (1) the relationship between caregiver pain interference with caregiver health-related quality of life (HRQOL), caregiver age, and service member/veteran (SMV) functional ability, and (2) change in caregiver pain interference longitudinally over 5 years. METHOD: Participants were 347 caregivers of SMVs diagnosed with traumatic brain injury (TBI). Caregivers completed the SF-12v2 Health Survey Bodily Pain scale at an initial baseline evaluation and up to four annual follow-up evaluations. Caregivers were divided into three pain interference groups: High Pain Interference (n = 104), Neutral Pain Interference (n = 117), and Low Pain Interference (n = 126). Caregivers also completed 15 HRQOL measures and a measure of SMV functional ability. RESULTS: The High Pain Interference group reported more clinically elevated scores on 13 measures compared to the Low Pain Interference group, and seven measures compared to the Neutral Pain Interference group. The Neutral Pain Interference group had more clinically elevated scores on three measures compared to the Low Pain Interference group. The High and Neutral Pain Interference groups were older than the Low Pain Interference group. Parent caregivers were older than intimate partner/sibling caregivers, but did not report worse pain interference. Caregiver age, and measures of Fatigue, Strain, Perceived Rejection, and Economic QOL were the strongest predictors of pain interference (p < .001), accounting for 28.2% of the variance. There was minimal change in Bodily Pain scores over five years. The interaction of time and age was not significant (X2 = 2.7, p = .61). CONCLUSION: It is important to examine pain in the context of HRQOL in caregivers, regardless of age.

Aortic Elasticity and Arsenic Exposure: A Step Function rather than a Linear Function.

While the dose-response relationship for the carcinogenic effects of arsenic exposure indicates nonlinearity with increases only above about 150 µg/L arsenic in drinking water, similar analyses of noncarcinogenic effects of arsenic exposure remain to be conducted. We present here an alternative analysis of data on a measure of aortic elasticity, a risk factor for hypertension, and its relationship to urinary arsenic levels. An occupational health study from Ankara, Turkey by Karakulak et al. compared urinary arsenic levels and a measure of aortic elasticity (specifically, aortic strain) in workers with a linear no-threshold model.  We have examined these data with three alternative models-a fitted step-function, a stratified, and a weighted linear regression model. Discontinuity within the data revealed two subsets of data, one for workers with urinary arsenic levels ≤ 160 µg/L whose mean aortic strain level was 11.3% and one for workers with arsenic levels > 160 µg/L whose mean aortic stain level was 5.33 % (p < 0.0001). Several alternative models were examined that indicated the best model to be the threshold model with a threshold at a urinary arsenic level of 160 µg/L. Observation of a discontinuity in the data revealed their better fit to a threshold model (at a urinary arsenic level of 160 µg/L) than to a linear-no threshold model.  Examinations with alternative models are recommended for studies of arsenic and hypertension and possibly other noncarcinogenic effects.

A review of low-dose arsenic risks and human cancers.

The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and "J-shaped" linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.

Designing research on concussion treatment in the military setting: Important challenges to consider.

Traumatic brain injury (TBI) is highly prevalent on a global scale with concussion being the most common of all TBIs. Concussion research on rehabilitation and symptom resolution is well-established, particularly among athletes, but less is known about the recovery of active duty service members (ADSMs). In a population whose occupational environment increases risk for such injury, it is imperative that treatment is optimized to achieve successful rehabilitation. The military setting, however, has challenges that must be accounted for when developing proposals to study the benefits of new interventions or treatment. This review will provide a discussion on those challenges to better understand the considerations that are essential during the developmental phase of concussion studies within the military setting. This review aims to provide investigators novice to the military setting an overview of considerations when researching concussion among ADSMs.

Provider Training in the Management of Headache Following Concussion Clinical Recommendation: Promoting a Standardized Means for Efficient Patient Recovery and Timely Return to Duty.

Background: Headache is a common symptom reported following concussion/mild traumatic brain injury. The Department of Defense's clinical recommendation (CR) describes guidance for primary care providers for the management of post-traumatic headache (PTH) in Service members. Objective: The objective of this study is to examine the association between training on the CR with provider clinical practice, patient behaviors, and symptom recovery. Methods: Participants were healthcare providers and two patient groups (one receiving care as usual [CAU] and another receiving care after provider training on PTH CR [CR+]). Providers were interviewed at three time points: (1) prior to CAU enrollment; (2) after CAU enrollment, but prior to training; and (3) after CR+ follow-up. Data from the second and third provider interview were used to evaluate a potential difference between provider practices pre- and post-training (n = 13). Patients were enrolled within 6 months of concussion. Patient outcomes (including neurobehavioral and headache symptoms) were assessed at three time-points: within 72 h (n = 35), at 1-week (n = 34) and at 1-month post-enrollment (n = 27). Results: Most follow-up care reported by providers were recommended within 72 h of initial visit post-training vs. >1 week pre-training. Additionally, providers reported a greater number of visits based on patient symptoms after training than before. Post-training, most providers reported referring patients to higher level of care "as needed," if not "very rarely," compared to 25% reported referrals prior to training. At 1-week post-enrollment the CR+ patient group reported more frequent medical provider visits compared to the CAU group. This trend was reversed at the 1-month follow-up whereby more CAU reported seeing a medical provider compared to CR+. By 1-week post-enrollment, fewer patients in the CR+ group reported being referred to any other providers or specialists compared to the CAU group. No differences in patient outcomes by provider training was found. Conclusion: The study results demonstrate the feasibility of training on the Management of Headache Following Concussion CR in order to change provider practices by promoting timely care, and promoting patient compliance as shown through improvement in follow-up visits and more monitoring within the primary care clinic.

Current patterns of primary care provider practices for the treatment of post-traumatic headache in active duty military settings.

OBJECTIVE: To provide a preliminary assessment of the current clinical practice for the treatment of post-traumatic headache following concussion in military primary health care settings. BACKGROUND: Headache is one of the most common symptoms post-concussion; however, little is known of the current clinical practices of primary care providers (on the treatment of post-traumatic headache), particularly in military settings. METHODS: Study participants were primary care providers (n = 65) who treated active duty Service members suffering from post-traumatic headache at two military installations. Qualitative data gathered via semi-structured interviews were used to describe provider practices and experience in treating patients with post-traumatic headache. RESULTS: Some patterns of care across primary care providers treating post-traumatic headache were consistent with the Department of Defense-recommended clinical recommendation (e.g., recommendation of both pharmacological and non-pharmacological treatment [89.4%]; engaging in follow-up care [100%]). Differences existed in timing of follow-up from initial visit [16.9% reporting within 24 hours; 21.5% reporting within 48-72 hours; and 26.2% reporting more than 1 week], the factors contributing to the type of care given (e.g., symptomatology [33.0%], injury characteristic [24.2%], patient characteristic [13.2%]) and the need for referral to higher level of care (e.g., symptomatology [44.6%], treatment failure [25.0%]). These variations may be indicative of individualized treatment which would be compliant with best clinical practice. CONCLUSION: The results of this study demonstrate the current clinical practice in military primary care settings for the treatment of post-traumatic headache which can potentially inform and improve implementation of provider training and education.

Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome.

BACKGROUND: Small for gestational age (SGA) is a well-known consequence of maternal smoking. Here, we newly examine the magnitude of SGA risk by week of gestational age. METHODS: Singleton live births (N = 3,032,928) with recorded birth weight, gestational age (22-44 weeks), and maternal tobacco use (Y/N) were categorized as to SGA (Y/N), based on 10th percentile gender-specific weights-for-age. RESULTS: SGA prevalence among tobacco users (19.5%) and non-users (9.1%) yielded a significant SGA prevalence rate ratio of 2.15 (2.13-2.16) and a significant adjusted odds ratio of 2.36 (2.34-2.38). The tobacco non-users' rate was steadily near 9% across the week 22-44 gestational age range. The tobacco users' rate was steady until week 33 when it rose monotonically through week 37 to about 20% at week 38 and remained high. This pattern for SGA by gestational week was similar for prevalence rates and adjusted ORs. Tobacco use only through week 33 was not seen to be an SGA risk factor. The magnitude of tobacco use as an SGA risk factor for late third trimester births increased during the period of preterm birth and became fully evident with a two-fold risk for full term infants. CONCLUSION: We newly report the temporal pattern of tobacco-related SGA by week of gestational age. Tobacco-related SGA was only seen for late third trimester births - increasing during weeks 33-37 with a doubling during weeks 38-44. This pattern, informative for issues of mechanism, highlights the potential benefit of extending tobacco cessation programs through the third trimester of pregnancy.

Traumatic Brain Injuries: Unreported and Untreated in an Army Population.

INTRODUCTION: In 2008, it was reported that 19.5% of service members previously deployed experienced a mild traumatic brain injury (mTBI). Fifty-seven percent of those did not seek medical care. It was suggested that concerns with seeking care involved confidentiality and career issues. Objective: This study addressed mTBI history, medical treatment history, and stigmas associated with mTBI/concussion. MATERIALS AND METHODS: An anonymous questionnaire was developed. Data collection occurred throughout March 2018 in conjunction with Brain Injury Awareness Month activities. RESULTS: All 5,174 volunteers were Army; 86% male; 87% were between 18 and 34 years old; 89% had <14 years in the military; 35% had a combat deployment; and 10% reported having one or more mTBIs in their military careers. Of the Soldiers who reported a concussion, 52% sought medical care. Of those not seeking care, 64% reported they did not think the injury required care, followed by 18% fearing negative impact on their career. Twenty-eight percent who experienced an mTBI versus 11% who have not reported that there is a stigma associated with an mTBI. CONCLUSIONS: Soldiers sometimes failed to report their suspected concussions and did not seek medical care. Educational efforts may increase reporting of and medical screening for potentially concussive events. Future research to determine the ramifications of unreported and untreated mTBIs/concussions is recommended.

Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water.

Background: Although inorganic arsenic in drinking water at high levels (100s-1000s µg/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited. Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were <200 ug/L with median <100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009-2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed. Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above. Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.

Assessment of developmental risk information on medicines for inclusion on the WHO's Essential Medicines List.

BACKGROUND: The WHO develops biannually an Essential Medicines List (EML) of medications proposed for national formularies to be safe, effective and cost-effective. This satisfies the priority healthcare needs of most adult populations, but it does not consider the unique toxicological risks that occur from exposures during pregnancy. METHODS: Developmental toxicity risk information for the 451 specific agents on the 2017 EML were identified from four well-recognized compendia of teratological assessments. On this basis, each agent was classified as having known, suggested, or little to no developmental risk, or as having insufficient information. RESULTS: Thirteen (3%) EML agents posed known developmental risks, and 115 (25%) had evidence suggesting risk. For 170 (38%) agents, there was little or no evidence of such risk. Thus, risk classification could be determined for 66% of the agents. For an additional 153 (34%) agents, the information was insufficient for classification. CONCLUSION: It is feasible to expand the classification of most of the EML agents to include the risks from exposure during pregnancy.

Trajectory of Postconcussive Symptoms 12 Months After Deployment in Soldiers With and Without Mild Traumatic Brain Injury: Warrior Strong Study.

We analyzed data from a cohort of recently deployed soldiers from 2 US Army bases, Fort Carson and Fort Bragg (2009 to 2015). Soldiers with and without a recent history of mild traumatic brain injury (mTBI) on deployment were evaluated within days of return and at 3, 6, and 12 months. Those with mTBI were more likely than those without to endorse ≥1 postconcussive symptom as "severe" and/or "very severe" (47% vs. 21%, baseline; adjusted relative risk (RR) = 1.71, 95% confidence interval: 1.51, 1.93, all time points), which remained significant after adjusting for posttraumatic stress disorder (adjusted RR = 1.34, 95% confidence interval: 1.20, 1.50). Prevalence and relative risks for 3 of the most common baseline symptoms remained constant over time: sleep problems (RR = 2.19), forgetfulness (RR = 2.56), and irritability (RR = 2.73). The pattern was slightly different for headache (baseline, RR = 3.44; 12 months, RR = 3.26), due to increased prevalence of headache in those without mTBI. The prevalence of clinically relevant postconcussive symptoms remained relatively constant over 1 year of follow-up, whether or not symptoms were associated with concussion. Service members with recent mTBI reported more symptoms than those without at all time points.

Lung Cancer Risk and Low (≤50 µg/L) Drinking Water Arsenic Levels for US Counties (2009⁻2013)-A Negative Association.

While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 µg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of.

Clues to predict incidental gallbladder cancer.

BACKGROUND: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. METHODS: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. RESULTS: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. CONCLUSIONS: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC.

Small-for-gestational age prevalence risk factors in central Appalachian states with mountain-top mining.

OBJECTIVES: To identify risk factors for small-for-gestational age (SGA) for counties in central Appalachian states (Kentucky (KY), Tennessee (TN), Virginia (VA), and West Virginia (WV)) with varied coal mining activities. MATERIAL AND METHODS: Live birth certificate files (1990-2002) were used for obtaining SGA prevalence rates for mothers based on the coal mining activities of their counties of residence, mountain-top mining (MTM) activities, underground mining activities but no mountain-top mining activity (non-MTM), or having no mining activities (non-mining). Co-variable information, including maternal tobacco use, was also obtained from the live birth certificate. Adjusted odds ratios were obtained using multivariable logistic regression comparing SGA prevalence rates for counties with coal mining activities to those without coal mining activities and comparing SGA prevalence rates for counties with coal mining activities for those with and without mountain-top mining activities. Comparisons were also made among those who had reported tobacco use and those who had not. RESULTS: Both tobacco use prevalence and SGA prevalence were significantly greater for mining counties than for non-mining counties and for MTM counties than for non-MTM counties. Adjustment for tobacco use alone explained 50% of the increased SGA risk for mining counties and 75% of the risk for MTM counties, including demographic pre-natal care co-variables that explained 75% of the increased SGA risk for mining counties and 100% of the risk for MTM. The increased risk of SGA was limited to the third trimester births among tobacco users and independent of the mining activities of their counties of residence. CONCLUSIONS: This study demonstrates that the increased prevalence of SGA among residents of counties with mining activity was primarily explained by the differences in maternal tobacco use prevalence, an effect that itself was gestational-age dependent. Self-reported tobacco use marked the population at the increased risk for SGA in central Appalachian states. Int J Occup Med Environ Health 2018;31(1):11-23.

Age-related differences pre-, intra-, and postcholecystectomy: A retrospective cohort study of 6,868 patients.

BACKGROUND: Cholecystectomy (CCY) is increasingly performed in older individuals. We sought to examine age-related differences in pre-, intra-, and postoperative factors at a community hospital, using a very large, single-institution cholecystectomy database. MATERIALS AND METHODS: A retrospective review of 6868 patients who underwent CCY from 2001 to 2013 was performed. ROC analysis identified the optimal age cutoff when complications reached a significant inflection point (<55 and ≥55 years). Multiple clinical features and outcomes were measured and compared by age. Logistic regression was used to examine how well a set of covariates predicted postoperative complications. RESULTS: Older patients had significantly higher rates of comorbidities and underwent more extensive preoperative imaging. Intraoperatively, older patients had more blood loss, longer operative times, and more open operations. Postoperatively, older patients experienced more complications and had significantly different pathological findings. While holding age and gender constant, regression analyses showed that preoperative creatinine level, blood loss and history of previous operation were the strongest predictors of complications. The risk for developing complications increased by 2% per year of life. CONCLUSION: Older patients have distinct pre-, intra-, and postoperative characteristics. Their care is more imaging- and cost-intensive. CCY in this population is associated with higher risks, likely due to a combination of comorbidities and age-related worsened physiological status. Pathologic findings are significantly different relative to younger patients. While removing the effect of age, preoperative creatinine levels, blood loss, and history of previous operation predict postoperative complications. Quantifying these differences may help to inform management decisions for older patients.

Arsenic in Drinking Water and Lung Cancer Mortality in the United States: An Analysis Based on US Counties and 30 Years of Observation (1950-1979).

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range of 3-59 µg/L. The upper-bound estimates of the risks are lower than the risks predicted from the SW Taiwan data and do not support those predictions. These results are consistent with a recent metaregression that indicated no increased lung cancer risk for arsenic exposures below 100-150 µg/L.

Effect of Residents on Operative Time and Complications: Focus on Laparoscopic Cholecystectomy in the Community.

OBJECTIVE: To better understand important aspects of resident education in the perioperative setting, given that there are conflicting data regarding resident training and outcomes (e.g., operative times and complications). To study continuity of care in a resident-run outpatient hospital clinic. DESIGN: Retrospective analysis of 2 databases. SETTING: The study was set up in a community teaching hospital. RESULTS: Of 4603 cases in a cholecystectomy database, 3302 (72%) were assisted by residents, with operative times ranging from 19 to 383 minutes, and 1576 (22.9%) were assisted by nonresidents. The average times were 93 and 77 minutes for resident- and non-resident-assisted cases, respectively. Complications were almost 3 times more likely for urgent vs. elective but were similar for resident-assisted vs. non-resident-assisted cases. The operative time was similar across PGY levels. Of 149 cases in a resident-run outpatient clinic, 100 (67%) of the residents participated in preoperative, intraoperative, and postoperative phases of case, but in only 4% of cases was it the same resident. CONCLUSION: Resident assistance increased operative times but not complications. Counterbalanced effects of increasing skill and increasing participation may explain this time stability across PGY levels. Continuity of care is preserved in the era of the 80-hour workweek, but not to a patient-specific degree.

A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water.

High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100-150 µg/L arsenic.

Predicting gangrenous cholecystitis.

BACKGROUND: Gangrenous cholecystitis (GC) is often challenging to treat. The objectives of this study were to determine the accuracy of pre-operative diagnosis, to assess the rate of post-cholecystectomy complications and to assess models to predict GC. METHODS: A retrospective single-institution review identified patients undergoing a cholecystectomy. Logistic regression models were used to examine the association of variables with GC and to build risk-assessment models. RESULTS: Of 5812 patients undergoing a cholecystectomy, 2219 had acute, 4837 chronic and 351 GC. Surgeons diagnosed GC pre-operatively in only 9% of cases. Patients with GC had more complications, including bile-duct injury, increased estimated blood loss (EBL) and more frequent open cholecystectomies. In unadjusted analyses, variables significantly associated with GC included: age >45 years, male gender, heart rate (HR) >90, white blood cell count (WBC) >13,000/mm(3), gallbladder wall thickening (GBWT) ≥ 4 mm, pericholecystic fluid (PCCF) and American Society of Anesthesiology (ASA) >2. In adjusted analyses, age, WBC, GBWT and HR, but not gender, PCCF or ASA remained statistically significant. A 5-point scoring system was created: 0 points gave a 2% probability of GC and 5 points a 63% probability. CONCLUSION: Using models can improve a diagnosis of GC pre-operatively. A prediction of GC pre-operatively may allow surgeons to be better prepared for a difficult operation.