Avanzando Caminos (Leading Pathways): Design and Procedures of The Hispanic/Latino Cancer Survivorship Study.

PURPOSE: Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. METHODS: Avanzando Caminos is a prospective, cohort-based study of 3,000 Hispanics/Latinos who completed primary cancer treatment within the past five years that is representative of the general Hispanic/Latino population in the U.S. Participants will complete self-report measures at baseline (T1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood draws to assess leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. CONCLUSIONS: Avanzando Caminos will fill critical gaps in knowledge to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.

A Surgical Desirability of Outcome Ranking (DOOR) Reveals Complex Relationships Between Race/Ethnicity, Insurance Type, and Neighborhood Deprivation.

OBJECTIVE: Develop an ordinal Desirability of Outcome Ranking (DOOR) for surgical outcomes to examine complex associations of Social Determinants of Health. BACKGROUND: Studies focused on single or binary composite outcomes may not detect health disparities. METHODS: Three health care system cohort study using NSQIP (2013-2019) linked with EHR and risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status and operative stress assessing associations of multilevel Social Determinants of Health of race/ethnicity, insurance type (Private 13,957; Medicare 15,198; Medicaid 2835; Uninsured 2963) and Area Deprivation Index (ADI) on DOOR and the binary Textbook Outcomes (TO). RESULTS: Patients living in highly deprived neighborhoods (ADI>85) had higher odds of PASC [adjusted odds ratio (aOR)=1.13, CI=1.02-1.25, P <0.001] and urgent/emergent cases (aOR=1.23, CI=1.16-1.31, P <0.001). Increased odds of higher/less desirable DOOR scores were associated with patients identifying as Black versus White and on Medicare, Medicaid or Uninsured versus Private insurance. Patients with ADI>85 had lower odds of TO (aOR=0.91, CI=0.85-0.97, P =0.006) until adjusting for insurance. In contrast, patients with ADI>85 had increased odds of higher DOOR (aOR=1.07, CI=1.01-1.14, P <0.021) after adjusting for insurance but similar odds after adjusting for PASC and urgent/emergent cases. CONCLUSIONS: DOOR revealed complex interactions between race/ethnicity, insurance type and neighborhood deprivation. ADI>85 was associated with higher odds of worse DOOR outcomes while TO failed to capture the effect of ADI. Our results suggest that presentation acuity is a critical determinant of worse outcomes in patients in highly deprived neighborhoods and without insurance. Including risk adjustment for living in deprived neighborhoods and urgent/emergent surgeries could improve the accuracy of quality metrics.

Association of Frailty and the Expanded Operative Stress Score with Preoperative Acute Serious Conditions, Complications, and Mortality in Males Compared to Females: A Retrospective Observational Study.

OBJECTIVE: The aim of this study was to expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males. SUMMARY BACKGROUND DATA: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1). METHODS: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90-, and 180-day mortality. RESULTS: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% were frail/very frail. Males had higher odds of PASC [adjusted odds ratio (aOR) = 1.31, 95% confidence interval (CI) = 1.21-1.41, P < 0.001] and severe/life-threatening Clavien-Dindo IV (CDIV) complications (aOR = 1.18, 95% CI = 1.09-1.28, P < 0.001). Although mortality rates were higher (all time-points, P < 0.001) in males versus females, mortality was similar after adjusting for frailty, OSS, and case status primarily due to increased male frailty scores. Additional adjustments for PASC and CDIV resulted in a lower odds of mortality in males (30-day, aOR = 0.81, 95% CI = 0.71-0.92, P = 0.002) that was most pronounced for males with PASC compared to females with PASC (30-day, aOR = 0.75, 95% CI = 0.56-0.99, P = 0.04). CONCLUSIONS: Similar to the male-dominated Veteran population, private sector, frail patients have high likelihood of postoperative mortality, even after low-stress surgeries. Preoperative frailty screening should be performed regardless of magnitude of the procedure. Despite males experiencing higher adjusted odds of PASC and CDIV complications, females with PASC had higher odds of mortality compared to males, suggesting differences in the aggressiveness of care provided to men and women.

Association of Insurance Type With Inpatient Surgery 30-Day Complications and Costs.

INTRODUCTION: Safety-net hospitals (SNHs) have higher postoperative complications and costs versus low-burden hospitals. Do low socioeconomic status/vulnerable patients receive care at lower-quality hospitals or are there factors beyond providers' control? We studied the association of private, Medicare, and vulnerable insurance type with complications/costs in a high-burden SNH. METHODS: Retrospective inpatient cohort study using National Surgical Quality Improvement Program (NSQIP) data (2013-2019) with cost data risk-adjusted by frailty, preoperative serious acute conditions (PASC), case status, and expanded operative stress score (OSS) to evaluate 30-day unplanned reoperations, any complication, Clavien-Dindo IV (CDIV) complications, and hospitalization variable costs. RESULTS: Cases (Private 1517; Medicare 1224; Vulnerable 3648) with patient mean age 52.3 y [standard deviation = 14.7] and 47.3% male. Adjusting for frailty and OSS, vulnerable patients had higher odds of PASC (aOR = 1.71, CI = 1.39-2.10, P < 0.001) versus private. Adjusting for frailty, PASC and OSS, Medicare (aOR = 1.27, CI = 1.06-1.53, P = 0.009), and vulnerable (aOR = 2.44, CI = 2.13-2.79, P < 0.001) patients were more likely to undergo urgent/emergent surgeries. Vulnerable patients had increased odds of reoperation and any complications versus private. Variable cost percentage change was similar between private and vulnerable after adjusting for case status. Urgent/emergent case status increased percentage change costs by 32.31%. We simulated "switching" numbers of private (3648) versus vulnerable (1517) cases resulting in an estimated variable cost of $49.275 million, a 25.2% decrease from the original $65.859 million. CONCLUSIONS: Increased presentation acuity (PASC and urgent/emergent surgeries) in vulnerable patients drive increased odds of complications and costs versus private, suggesting factors beyond providers' control. The greatest impact on outcomes may be from decreasing the incidence of urgent/emergent surgeries by improving access to care.

Sex-Related Differences in Acuity and Postoperative Complications, Mortality and Failure to Rescue.

INTRODUCTION: Yentl syndrome describing sex-related disparities has been extensively studied in medical conditions but not after surgery. This retrospective cohort study assessed the association of sex, frailty, presenting with preoperative acute serious conditions (PASC), and the expanded Operative Stress Score (OSS) with postoperative complications, mortality, and failure-to-rescue. METHODS: The National Surgical Quality Improvement Program from 2015 to 2019 evaluating 30-d complications, mortality, and failure-to-rescue. RESULTS: Of 4,860,308 cases (43% were male; mean [standard deviation] age of 56 [17] y), 6.0 and 0.8% were frail and very frail, respectively. Frailty score distribution was higher in men versus women (P < 0.001). Most cases were low-stress OSS2 (44.9%) or moderate-stress OSS3 (44.5%) surgeries. While unadjusted 30-d mortality rates were higher (P < 0.001) in males (1.1%) versus females (0.8%), males had lower odds of mortality (adjusted odds ratio (aOR) = 0.92, 95% confidence interval [CI] = 0.90-0.94, P < 0.001) after adjusting for frailty, OSS, case status, PASC, and Clavien-Dindo IV (CDIV) complications. Males have higher odds of PASC (aOR = 1.33, CI = 1.31-1.35, P < 0.001) and CDIV complications (aOR = 1.13, CI = 1.12-1.15, P < 0.001). Male-PASC (aOR = 0.76, CI = 0.72-0.80, P < 0.001) and male-CDIV (aOR = 0.87, CI = 0.83-0.91, P < 0.001) interaction terms demonstrated that the increased odds of mortality associated with PASC or CDIV complications/failure-to-rescue were lower in males versus females. CONCLUSIONS: Our study provides a comprehensive analysis of sex-related surgical outcomes across a wide range of procedures and health care systems. Females presenting with PASC or experiencing CDIV complications had higher odds of mortality/failure to rescue suggesting sex-related care differences. Yentl syndrome may be present in surgical patients; possibly related to differences in presenting symptoms, patient care preferences, or less aggressive care in female patients and deserves further study.

Absolute Prostate Specific Antigen after 6 Months of Androgen Deprivation Therapy Is a Predictor of Overall and Cancer-Specific Mortality in Men with Hormone-Sensitive Prostate Cancer.

PURPOSE: We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. MATERIALS AND METHODS: We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. RESULTS: We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). CONCLUSIONS: Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

Educating Primary Care Providers and Associate Care Providers About Hepatitis C Screening of Baby Boomers: a Multi-practice Study.

Chronic hepatitis C virus (HCV) increases the risk for hepatocellular carcinoma. Despite higher prevalence of HCV in persons born 1945-1965 (baby boomer), screening has not been widely adopted. Both primary care providers (PCPs) and associate care providers (ACPs) need to be educated about the rationale and methods to screen for HCV. In five Federally Qualified Health Centers serving low-income Hispanic communities, PCPs and ACPs attended a 50-min training lecture about HCV epidemiology, screening methods, and evaluation. Using a 12-item questionnaire, knowledge and attitudes were compared for PCPs and ACPs at baseline (pre-test) and following training (post-test). A higher proportion of PCPs correctly answered 3 of 6 knowledge questions on both pre-test and post-test but ACPs' showed more improvement in knowledge (all P < 0.05). ACPs had more favorable attitudes about linking patients to care on pre- and post-tests than PCPs, and ACPs' attitudes improved on all 6 items versus 4 for PCPs. Both PCPs and ACPs improved knowledge and attitudes after training about HCV screening but ACPs had more favorable attitudes than PCPs. Engaging the entire primary care practice team in learning about HCV screening promotes knowledge and attitudes necessary for successful implementation.

Persistent Pain, Physical Dysfunction, and Decreased Quality of Life After Combat Extremity Vascular Trauma.

BACKGROUND: Combat-related extremity vascular injuries (EVI) have long-lasting impact on Iraq/Afghanistan veterans. The purpose of this study is to describe long-term functional outcomes in veterans with EVI using survey measures and identify modifiable factors that may be improved to reduce chronic pain and injury-related dysfunction. METHODS: Veterans with upper and lower EVI undergoing an initial limb salvage attempt were identified using the Department of Defense Trauma Registry and validated with chart abstraction. Surveys measured pain; Short Musculoskeletal Function Assessment (SMFA) for self-reported bother and dysfunction; and Veterans RAND 12-Item Health Survey (VR-12) physical and mental component scores (PCS; MCS) for quality of life, depression, post-traumatic stress disorder, and the potentially modifiable factors of reintegration into civilian life, resilient coping, resilience, and family functioning. RESULTS: Eighty-one patients responded with an average time since injury of 129 months (SD: 31; range 67-180 months). Mechanism of injury included 64% explosions and 31% gunshot wounds; 16% of the respondents were diagnosed with moderate/severe/penetrating traumatic brain injury. Limb salvage rates were 100% and 77% for upper and lower extremities, respectively (P = 0.004). Respondents screened positive for probable depression (55%) and post-traumatic stress disorder (51%). Compared with population norms, SMFA bother and dysfunction indices were higher (worse), MCS was lower (worse), and PCS was similar. The multivariable models adjusted for age, marital status and pain. The higher SMFA is part of the results of the multivariable models. MCS decreased with difficulty reintegrating into civilian life and was positively correlated with increased resilience and resilient coping. SMFA scores were greater for patients with high pain intensity and increased 6-11 points per point increase in difficulty with civilian-life reintegration. SMFA dysfunction was associated with better family functioning. CONCLUSIONS: EVI results in significant long-term disability with lasting deficits in physical function, frequent depressive symptoms, and below average self-reported quality of life. Strengthening modifiable factors including resiliency and resilient coping, and providing ongoing assistance to improve reintegration into civilian life, may ameliorate the functional disabilities and chronic pain experienced by veterans with EVI.

Health Phenotypes and Neurobehavioral Symptom Severity Among Post-9/11 Veterans With Mild Traumatic Brain Injury: A Chronic Effects of Neurotrauma Consortium Study.

OBJECTIVE: To evaluate whether neurobehavioral symptoms differ between groups of veterans with mild traumatic brain injury (mTBI) classified by health characteristics. PARTICIPANTS: A total of 71 934 post-9/11 veterans with mTBI from the Chronic Effects of Neurotrauma Consortium Epidemiology warfighter cohort. DESIGN: Cross-sectional analysis of retrospective cohort. MAIN MEASURES: Health phenotypes identified using latent class analysis of health and function over 5 years. Symptom severity measured using Neurobehavioral Symptom Inventory; domains included vestibular, somatic, cognitive, and affective. RESULTS: Veterans classified as moderately healthy had the lowest symptom burden while the polytrauma phenotype group had the highest. After accounting for sociodemographic and injury characteristics, polytrauma phenotype veterans had about 3 times the odds of reporting severe symptoms in each domain compared with moderately healthy veterans. Those veterans who were initially moderately healthy but whose health declined over time had about twice the odds of severe symptoms as consistently healthier Veterans. The strongest associations were in the affective domain. Compared with the moderately healthy group, veterans in other phenotypes were more likely to report symptoms substantially interfered with their daily lives (odds ratio range: 1.3-2.8). CONCLUSION: Symptom severity and interference varied by phenotype, including between veterans with stable and declining health. Ameliorating severe symptoms, particularly in the affective domain, could improve health trajectories following mTBI.

A geriatrics walking clinic improves hemoglobin A1c and timed gait in older veterans with type 2 diabetes.

Over one quarter of older adults in the U.S. has diabetes; and, physical activity is important for the promotion of healthy aging in this population. The purpose of this clinical demonstration project is to evaluate the effect of physical activity in the form of walking on glycemic control and timed gait in older Veterans with type 2 diabetes (T2D). Veterans aged ≥60 years were enrolled in the Geriatrics Walking Clinic (GWC), a clinical demonstration project, at South Texas Veterans Health Care System. GWC is a 6-week clinical program that promotes physical activity and is delivered by a registered nurse/diabetes educator and geriatrician. Veterans were recruited from the VA clinics. Enrolled patients received a pedometer at an initial face-to-face visit, were followed with weekly phone calls to monitor steps/day, received encouragement, and participated in a final face-to-face visit at the end of 6 weeks. In a sub-set of patients with T2D, we performed a chart review and recorded Hemoglobin A1c (HbA1c) at 3, 6, and 12 months after completion of the program. Timed Gait, a major characteristic of frailty, was measured at baseline and after completing the program. Change in HbA1c and timed gait compared to baseline was examined using paired t-tests. Sixty-two patients had HbA1c values available and were included in this analysis. Of these, 36, 52, and 61 patients had repeat HbA1c at 3, 6, and 12 months after the intervention, respectively. Mean age was 68 ± 6 years, 58% were Hispanic, and 92% males. HbA1c improved at 3 months (-0.49, 95% CI: -0.87 to -0.12, p=0.013), at 6 months (-0.40, 95% CI: -0.68 to -0.12, p=0.006), and at 12 months (-0.30, 95% CI: -0.57 to -0.029, p=0.031) compared to baseline. Timed Gait also improved (9.3 ±1.7 vs. 10.2 ±1.8, p<0.001). The finding highlights that older patients with T2D benefit from a GWC with improved glycemic control and timed gait.

Joint trajectories of cognition and gait speed in Mexican American and European American older adults: The San Antonio longitudinal study of aging.

OBJECTIVES: Cognitive decline and gait speed slowing are independent predictors of disability and mortality. While both factors increase in prevalence with advancing age, little is known about their combined patterns of change. The study goal was to identify joint trajectories of cognition and gait speed within an aging bi-ethnic cohort of Mexican Americans and European Americans. METHODS/DESIGN: Participants included 182 Mexican Americans and 188 European Americans, ages 65 to 74, who were followed over a mean of 9.5 years. Cognition was assessed with the mini-mental state examination and gait speed was examined with a timed 10-ft walk. Joint trajectory classes of cognition and gait speed were identified with latent growth mixture modeling. Odd-ratios assessed predictors for trajectory classes. RESULTS: Three latent trajectory classes were identified: (a) relatively stable cognition and gait (termed stable cognition and gait class, 65.4%); (b) deteriorating cognition and gait (termed cognitive and physical vulnerability class, 22.2%); (c) stable cognition and deteriorating gait (termed physical vulnerability class, 12.4%). The odds of classification in the cognitive and physical vulnerability class vs stable cognition and gait class was associated with Mexican American ethnicity (OR = 3.771, P = .016), age (OR = 1.186, P = .017), income (OR = 0.828, P = .029), education (OR = 0.703, P < .001), and diabetes (OR = 4.547, P = .010). The odds of classification in the physical vulnerability class was associated with female sex (OR = 6.481, P = .004) and body mass index (OR = 1.118, P = .025). CONCLUSIONS: The trajectories of cognition and gait speed were generally parallel, suggesting the two domains may act synergistically to shape important health outcomes. Socioeconomic disparities and Mexican American ethnicity independently conferred risk for accelerated decline.

Machine learning outcome regression improves doubly robust estimation of average causal effects.

BACKGROUND: Doubly robust estimation produces an unbiased estimator for the average treatment effect unless both propensity score (PS) and outcome models are incorrectly specified. Studies have shown that the doubly robust estimator is subject to more bias than the standard weighting estimator when both PS and outcome models are incorrectly specified. METHOD: We evaluated whether various machine learning methods can be used for estimating conditional means of the potential outcomes to enhance the robustness of the doubly robust estimator to various degrees of model misspecification in terms of reducing bias and standard error. We considered four types of methods to predict the outcomes: least squares, tree-based methods, generalized additive models and shrinkage methods. We also considered an ensemble method called the Super Learner (SL), which is a linear combination of multiple learners. We conducted simulations considering different scenarios by the complexity of PS and outcome-generating models and some ranges of treatment prevalence. RESULTS: The shrinkage methods performed well with robust doubly robust estimates in term of bias and mean squared error across the scenarios when the models became rich by including all 2-way interactions of the covariates. The SL performed similarly to the best method in each scenario. CONCLUSIONS: Our findings indicate that machine learning methods such as the SL or the shrinkage methods using interaction models should be used for more accurate doubly robust estimators.

Serum microRNA profiles among dioxin exposed veterans with monoclonal gammopathy of undetermined significance.

Previously an increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), was reported among Vietnam veterans exposed to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dysregulated expression of certain microRNAs (miRNAs) was demonstrated in MGUS and MM. Given the important role of miRNAs in cellular homeostasis, the aim of this study was to determine if there was an association between serum levels of selected miRNAs and TCDD in 47 MGUS cases identified in our previous investigation using serum specimens and exposure data archived by the Air Force Health Study (AFHS). A total of 13 miRNA levels (let-7a, let-7i, miR-16, miR-20a, miR-21, miR-34a, miR-106b, miR-146a, miR-181a, miR-192, miR-205, miR-335, and miR-361) was measured in serum stored during the 2002 AFHS follow-up and the relationship to lipid-adjusted serum TCDD levels in 1987 was determined. miR-34a showed the strongest relationship with TCDD; after age-adjustment, this positive association was more pronounced. In contrast, the other 12 miRNAs displayed absolute values of age adjusted coefficient estimates below 1.16 and non-significant p-values. The observed strong positive association between high body burdens of TCDD and miR-34a, a tumor suppressor regulated by p53, in this MGUS population warrants clarification of the TCDD-miR-34a relationship and its role in the pathogenesis of MGUS and risk for MM.

Significant Increase in Risk of Fibrosis or Cirrhosis at Time of HCV Diagnosis for Hispanics With Diabetes and Obesity Compared With Other Ethnic Groups.

BACKGROUND & AIMS: Advanced liver disease, which includes fibrosis and cirrhosis, has been reported to be more prevalent in Hispanics patients at the time of diagnosis of chronic hepatitis C virus (HCV) infection than non-Hispanic black or non-Hispanic white patients. We performed a propensity score-matched analysis to determine whether metabolic risk factors contribute to this disparity. METHODS: We collected data from persons with 748 HCV infection (22% Hispanic, 53% non-Hispanic black, and 26% non-Hispanic white; 23% with advanced liver disease), born from 1945 through 1965, diagnosed at 6 health care systems in Texas. Advanced liver disease was defined as a FIB-4 index score above 3.25. We examined the association between advanced liver disease and race or ethnicity, metabolic risk (based on diabetes mellitus and body mass index [BMI]) and heavy alcohol use in propensity score-matched analyses. RESULTS: In propensity-score matched models, among those who were obese (BMI ≥30) with a diagnosis of diabetes, the adjusted odds ratio of advanced liver disease for Hispanics vs non-Hispanic black was 7.89 (95% CI, 3.66-17.01) and adjusted odds ratio = 12.49 (95% CI, 3.24-48.18) for Hispanic vs non-Hispanic white patients (both P < .001). CONCLUSIONS: HCV-infected Hispanics with obesity and diabetes have a far higher risk for advanced liver disease than other racial or ethnic groups. These findings highlight the need for HCV treatment and management of probable concurrent fatty liver disease. Even after we accounted for metabolic risk factors, Hispanics were still at higher risk for advanced liver disease, indicating the potential involvement of other factors such as genetic variants.

Targeted use of growth mixture modeling: a learning perspective.

From the statistical learning perspective, this paper shows a new direction for the use of growth mixture modeling (GMM), a method of identifying latent subpopulations that manifest heterogeneous outcome trajectories. In the proposed approach, we utilize the benefits of the conventional use of GMM for the purpose of generating potential candidate models based on empirical model fitting, which can be viewed as unsupervised learning. We then evaluate candidate GMM models on the basis of a direct measure of success; how well the trajectory types are predicted by clinically and demographically relevant baseline features, which can be viewed as supervised learning. We examine the proposed approach focusing on a particular utility of latent trajectory classes, as outcomes that can be used as valid prediction targets in clinical prognostic models. Our approach is illustrated using data from the Longitudinal Assessment of Manic Symptoms study. Copyright © 2016 John Wiley & Sons, Ltd.

A retrospective cohort study of comorbidity trajectories associated with traumatic brain injury in veterans of the Iraq and Afghanistan wars.

OBJECTIVES: To identify and validate trajectories of comorbidity associated with traumatic brain injury in male and female Iraq and Afghanistan war Veterans (IAV). METHODS: Derivation and validation cohorts were compiled of IAV who entered the Department of Veterans Affairs (VA) care and received 3 years of VA care between 2002-2011. Chronic disease and comorbidities associated with deployment including TBI were identified using diagnosis codes. A latent class analysis (LCA) of longitudinal comorbidity data was used to identify trajectories of comorbidity. RESULTS: LCA revealed five trajectories that were similar for women and men: (1) Healthy, (2) Chronic Disease, (3) Mental Health, (4) Pain and (5) Polytrauma Clinical Triad (PCT: pain, mental health and TBI). Two additional classes found in men were 6) Minor Chronic and 7) PCT with chronic disease. Among these gender-stratified trajectories, it was found that women were more likely to experience headache (Pain trajectory) and depression (Mental Health trajectory), while men were more likely to experience lower back pain (Pain trajectory) and substance use disorder (Mental Health trajectory). The probability of TBI was highest in the PCT-related trajectories, with significantly lower probabilities in other trajectories. CONCLUSIONS: It was found that TBI was most common in PCT-related trajectories, indicating that TBI is commonly comorbid with pain and mental health conditions for both men and women. The relatively young age of this cohort raises important questions regarding how disease burden, including the possibility of neurodegenerative sequelae, will accrue alongside normal age-related decline in individuals with TBI. Additional 'big data' methods and a longer observation period may allow the development of predictive models to identify individuals with TBI that are at-risk for adverse outcomes.

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults.

BACKGROUND: Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. OBJECTIVE: To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. RESEARCH DESIGN: This was a retrospective cohort study. PARTICIPANTS: Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. INTERVENTION: We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. MAIN MEASURES: Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity. KEY RESULTS: A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. CONCLUSIONS: Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

Application of a methicillin-resistant Staphylococcus aureus risk score for community-onset pneumonia patients and outcomes with initial treatment.

BACKGROUND: Community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an evolving problem, and there is a great need for a reliable method to assess MRSA risk at hospital admission. A new MRSA prediction score classifies CO-pneumonia patients into low, medium, and high-risk groups based on objective criteria available at baseline. Our objective was to assess the effect of initial MRSA therapy on mortality in these three risk groups. METHODS: We conducted a retrospective cohort study using data from the Veterans Health Administration (VHA). Patients were included if they were hospitalized with pneumonia and received antibiotics within the first 48 h of admission. They were stratified into MRSA therapy and no MRSA therapy treatment arms based on antibiotics received in the first 48 h. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: A total of 80,330 patients met inclusion criteria, of which 36% received MRSA therapy and 64% did not receive MRSA therapy. The majority of patients were classified as either low (51%) or medium (47%) risk, with only 2% classified as high-risk. Multivariable logistic regression analysis demonstrated that initial MRSA therapy was associated with a lower 30-day mortality in the high-risk group (adjusted odds ratio 0.57; 95% confidence interval 0.42-0.77). Initial MRSA therapy was not beneficial in the low or medium-risk groups. CONCLUSIONS: This study demonstrated improved survival with initial MRSA therapy in high-risk CO-pneumonia patients. The MRSA risk score might help spare MRSA therapy for only those patients who are likely to benefit.

Serious mental illnesses associated with receipt of surgery in retrospective analysis of patients in the Veterans Health Administration.

BACKGROUND: The STOPP study (Surgical Treatment Outcomes for Patients with Psychiatric Disorders) analyzed variation in rates and types of major surgery by serious mental illness status among patients treated in the Veterans Health Administration (VA). VA patients are veterans of United States military service who qualify for federal care by reason of disability, special service experiences, or poverty. METHODS: STOPP conducted a secondary data analysis of medical record extracts for seven million VA patients treated Oct 2005-Sep 2009. The retrospective study aggregated inpatient surgery events, comorbid diagnoses, demographics, and postoperative 30-day mortality. RESULTS: Serious mental illness -- schizophrenia, bipolar disorder, posttraumatic stress disorder, or major depressive disorder, was identified in 12 % of VA patients. Over the 4-year study period, 321,131 patients (4.5 %) underwent surgery with same-day preoperative or immediate post-operative admission including14 % with serious mental illness. Surgery patients were older (64 vs. 61 years) and more commonly African-American, unmarried, impoverished, highly disabled (24 % vs 12 % were Priority 1), obese, with psychotic disorder (4.3 % vs 2.9 %). Among surgery patients, 3.7 % died within 30 days postop. After covariate adjustment, patients with pre-existing serious mental illness were relatively less likely to receive surgery (adjusted odds ratios 0.4-0.7). CONCLUSIONS: VA patients undergoing major surgery appeared, in models controlling for comorbidity and demographics, to disproportionately exclude those with serious mental illness. While VA preferentially treats the most economically and medically disadvantaged veterans, the surgery subpopulation may be especially ill, potentially warranting increased postoperative surveillance.

Complex comorbidity clusters in OEF/OIF veterans: the polytrauma clinical triad and beyond.

BACKGROUND: A growing body of research on US Veterans from Afghanistan and Iraq [Operations Enduring and Iraqi Freedom, and Operation New Dawn (OEF/OIF)] has described the polytrauma clinical triad (PCT): traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and pain. Extant research has not explored comorbidity clusters in this population more broadly, particularly co-occurring chronic diseases. OBJECTIVES: The aim of the study was to identify comorbidity clusters among diagnoses of deployment-specific (TBI, PTSD, pain) and chronic (eg, hypertension, diabetes) conditions, and to examine the association of these clusters with health care utilization and adverse outcomes. RESEARCH DESIGN: This was a retrospective cohort study. SUBJECTS: The cohort comprised OEF/OIF Veterans who received care in the Veterans Health Administration in fiscal years (FY) 2008-2010. MEASURES: We identified comorbidity using validated ICD-9-CM code-based algorithms and FY08-09 data, followed by which we applied latent class analysis to identify the most statistically distinct and clinically meaningful patterns of comorbidity. We examined the association of these clusters with process measures/outcomes using logistic regression to correlate medication use, acute health care utilization, and adverse outcomes in FY10. RESULTS: In this cohort (N=191,797), we found 6 comorbidity clusters. Cluster 1: PCT+Chronic Disease (5%); Cluster 2: PCT (9%); Cluster 3: Mental Health+Substance Abuse (24%); Cluster 4: Sleep, Amputation, Chronic Disease (4%); Cluster 5: Pain, Moderate PTSD (6%); and Cluster 6: Relatively Healthy (53%). Subsequent health care utilization patterns and adverse events were consistent with disease patterns. CONCLUSIONS: These comorbidity clusters extend beyond the PCT and may be used as a foundation to examine coordination/quality of care and outcomes for OEF/OIF Veterans with different patterns of comorbidity.