Using joint probability density to create most informative unidimensional indices: a new method using pain and psychiatric severity as examples.

BACKGROUND: Dimension reduction methods do not always reduce their underlying indicators to a single composite score. Furthermore, such methods are usually based on optimality criteria that require discarding some information. We suggest, under some conditions, to use the joint probability density function (joint pdf or JPD) of p-dimensional random variable (the p indicators), as an index or a composite score. It is proved that this index is more informative than any alternative composite score. In two examples, we compare the JPD index with some alternatives constructed from traditional methods. METHODS: We develop a probabilistic unsupervised dimension reduction method based on the probability density of multivariate data. We show that the conditional distribution of the variables given JPD is uniform, implying that the JPD is the most informative scalar summary under the most common notions of information. B. We show under some widely plausible conditions, JPD can be used as an index. To use JPD as an index, in addition to having a plausible interpretation, all the random variables should have approximately the same direction(unidirectionality) as the density values (codirectionality). We applied these ideas to two data sets: first, on the 7 Brief Pain Inventory Interference scale (BPI-I) items obtained from 8,889 US Veterans with chronic pain and, second, on a novel measure based on administrative data for 912 US Veterans. To estimate the JPD in both examples, among the available JPD estimation methods, we used its conditional specifications, identified a well-fitted parametric model for each factored conditional (regression) specification, and, by maximizing the corresponding likelihoods, estimated their parameters. Due to the non-uniqueness of conditional specification, the average of all estimated conditional specifications was used as the final estimate. Since a prevalent common use of indices is ranking, we used measures of monotone dependence [e.g., Spearman's rank correlation (rho)] to assess the strength of unidirectionality and co-directionality. Finally, we cross-validate the JPD score against variance-covariance-based scores (factor scores in unidimensional models), and the "person's parameter" estimates of (Generalized) Partial Credit and Graded Response IRT models. We used Pearson Divergence as a measure of information and Shannon's entropy to compare uncertainties (informativeness) in these alternative scores. RESULTS: An unsupervised dimension reduction was developed based on the joint probability density (JPD) of the multi-dimensional data. The JPD, under regularity conditions, may be used as an index. For the well-established Brief Pain Interference Inventory (BPI-I (the short form with 7 Items) and for a new mental health severity index (MoPSI) with 6 indicators, we estimated the JPD scoring. We compared, assuming unidimensionality, factor scores, Person's scores of the Partial Credit model, the Generalized Partial Credit model, and the Graded Response model with JPD scoring. As expected, all scores' rankings in both examples were monotonically dependent with various strengths. Shannon entropy was the smallest for JPD scores. Pearson Divergence of the estimated densities of different indices against uniform distribution was maximum for JPD scoring. CONCLUSIONS: An unsupervised probabilistic dimension reduction is possible. When appropriate, the joint probability density function can be used as the most informative index. Model specification and estimation and steps to implement the scoring were demonstrated. As expected, when the required assumption in factor analysis and IRT models are satisfied, JPD scoring agrees with these established scores. However, when these assumptions are violated, JPD scores preserve all the information in the indicators with minimal assumption.

What Contributes to Sustainability? Examining Access to Medications for Opioid Use Disorder in Low-Adopting VHA Facilities.

BACKGROUND: Successful implementation can increase the availability of evidence-based treatments but continued patient access can be threatened if there is not deliberate focus on sustainment. Real-world examples are needed to elucidate contributors to sustainability. OBJECTIVE: We examined sustainability of outcomes of a study which tested a 12-month external facilitation intervention. The study evaluated change in access to medications for opioid use disorder (MOUD) in Veterans Health Administration (VHA) facilities in the lowest quartile of MOUD prescribing. DESIGN: Convergent mixed-methods design. PARTICIPANTS: Thirty-nine providers and leaders from eight VHA facilities. APPROACH: Thirty-minute post-implementation telephone interviews explored whether barriers identified pre-implementation were successfully addressed, the presence of any new challenges, helpfulness of external facilitation, and plans for sustaining MOUD access. Interviews were analyzed using a rapid turn-around approach. VHA administrative data were used to characterize the facilities and assess their ratio of patients with an OUD diagnosis receiving MOUD (MOUD/OUD ratio) at the end of a 9-month sustainability period. KEY RESULTS: Commonly reported contributors to sustained MOUD access included national attention on the opioid epidemic, accountability created by study participation, culture shift in MOUD acceptability, leadership support, and plans to build on initial progress. Frequently reported barriers included staffing issues and lack of MOUD-devoted time; the need to overhaul existing policies, practices, and/or processes; and fear and anxiety about MOUD prescribing. All facilities either maintained MOUD/OUD ratio improvement (n = 2) or further improved (n = 6) at the end of sustainability. Facilities with the highest and lowest ratio at the end of sustainability used a team-based approach to MOUD delivery; however, organizational setting differences may have impacted overall MOUD access. CONCLUSIONS: Ensuring stable and consistent staff, and sufficient time dedicated to MOUD are critical to sustaining access to evidence-based treatment in low-adopting facilities. This study highlights the importance of investing in local, system-level changes to improve and sustain access to effective treatments.

Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD): an Implementation Trial in Eight Veterans Health Administration Facilities.

BACKGROUND: Identifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD. OBJECTIVE: Determine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls. DESIGN: Pre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention. PARTICIPANTS: VHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block. INTERVENTION: External facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation. MAIN MEASURES: Pre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities. KEY RESULTS: Intervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: - 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls. CONCLUSIONS: Intensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.

Impact of different cover letter information and incentives on Veterans' emotional responses to an unsolicited mailed survey about military traumas: a randomized, 3x2x2 factorial trial.

BACKGROUND: Altering cover letter information to reduce non-response bias in trauma research could inadvertently leave survey participants unprepared for potentially upsetting questions. In an unsolicited, mailed survey, we assessed participants' change in affect post-survey after altering key cover letter information and promising different incentives. We tested direct and indirect effects of participants carefully reading the cover letter on changes in their affect post-survey. METHODS: In a 3X2X2 randomized, factorial trial, 480 male and 480 female, nationally representative Veterans who were applying for posttraumatic stress disorder disability benefits were randomized to receive one of 12 different cover letters. The cover letters provided general versus more explicit information about the survey's trauma content and how their names were selected for study; we also promised different incentives for returning the survey. The main outcome was change in affect post-survey. We examined five potential moderators: combat or military sexual trauma exposure, posttraumatic stress disorder or serious mental illness diagnosis, and recency of military service. Mediators between reading the cover letter carefully and post-survey affect included how participants rated the cover letters' information and whether they thought the cover letters prepared them for the survey's content. A Bonferroni corrected alpha of 0.003 was the threshold for statistical significance. RESULTS: One hundred ninety men and 193 women reported their pre-and post-survey affect. Across all study conditions, out of 16 possible points, the net change in affect post-survey was less than a quarter-point for men and women. Mean changes in post-survey affect did not differ statistically significantly across any of the study factors (ps > 0.06); nor were there statistically significant interactions between any of the study factors and the 5 moderators after accounting for multiple comparisons (ps > 0.02). After controlling for pre-survey affect, reading the cover letter carefully had small effects on changes in post-survey affect, with larger associations seen in the women compared to men. Mediators' effects were often in opposite directions for men and women. CONCLUSION: General descriptions of a survey's trauma content appear ethically defensible. Research on cover letters' impacts on survey participants' emotional reactions and how those impacts differ by gender is needed.

Impact of different cover letter content and incentives on non-response bias in a sample of Veterans applying for Department of Veterans Affairs disability benefits: a randomized, 3X2X2 factorial trial.

BACKGROUND: Non-random non-response bias in surveys requires time-consuming, complicated, post-survey analyses. Our goal was to see if modifying cover letter information would prevent non-random non-response bias altogether. Our secondary goal tested whether larger incentives would reduce non-response bias. METHODS: A mailed, survey of 480 male and 480 female, nationally representative, Operations Enduring Freedom, Iraqi Freedom, or New Dawn (OEF/OIF/OND) Veterans applying for Department of Veterans Affairs (VA) disability benefits for posttraumatic stress disorder (PTSD). Cover letters conveyed different information about the survey's topics (combat, unwanted sexual attention, or lifetime and military experiences), how Veterans' names had been selected (list of OEF/OIF/OND Veterans or list of Veterans applying for disability benefits), and what incentive Veterans would receive ($20 or $40). The main outcome, non-response bias, measured differences between survey respondents' and sampling frame's characteristics on 8 administrative variables, including Veterans' receipt of VA disability benefits and exposure to combat or military sexual trauma. Analysis was intention to treat. We used ANOVA for factorial block-design, logistic, mixed-models to assess bias and multiple imputation and expectation-maximization algorithms to assess potential missing mechanisms (missing completely at random, missing at random, or not random) of two self-reported variables: combat and military sexual assault. RESULTS: Regardless of intervention, men with any VA disability benefits, women with PTSD disability benefits, and women with combat exposure were over-represented among respondents. Interventions explained 0.0 to 31.2% of men's variance and 0.6 to 30.5% of women's variance in combat non-response bias and 10.2 to 43.0% of men's variance and 0.4 to 31.9% of women's variance in military sexual trauma non-response bias. Non-random assumptions showed that men's self-reported combat exposure was overestimated by 19.0 to 28.8 percentage points and their self-reported military sexual assault exposure was underestimated by 14.2 to 28.4 percentage points compared to random missingness assumptions. Women's self-reported combat exposure was overestimated by 8.6 to 10.6 percentage points and military sexual assault exposure, by 1.2 to 6.9 percentage points. CONCLUSIONS: Our interventions reduced bias in some characteristics, leaving others unaffected or exacerbated. Regardless of topic, researchers are urged to present estimates that include all three assumptions of missingness.

Reversals in initially denied Department of Veterans Affairs' PTSD disability claims after 17 years: a cohort study of gender differences.

BACKGROUND: In 2011, the Department of Veterans Affairs (VA) strengthened its disability claims processes for military sexual trauma, hoping to reduce gender differences in initial posttraumatic stress disorder (PTSD) disability awards. These process improvements should also have helped women reverse previously denied claims and, potentially, diminished gender discrepancies in appealed claims' outcomes. Our objectives were to examine gender differences in reversals of denied PTSD claims' outcomes after 2011, determine whether disability awards (also known as "service connection") for other disorders offset any PTSD gender discrepancy, and identify mediating confounders that could explain any persisting discrepancy. METHODS: From a nationally representative cohort created in 1998, we examined service connection outcomes in 253 men and 663 women whose initial PTSD claims were denied. The primary outcome was PTSD service connection as of August 24, 2016. Secondary outcomes were service connection for any disorder and total disability rating. The total disability rating determines the generosity of Veterans' benefits. RESULTS: 51.4% of men and 31.3% of women were service connected for PTSD by study's end (p < 0.001). At inception, 54.2% of men and 63.2% of women had any service connection-i.e., service connection for disorders other than PTSD (p = 0.01) and similar total disability ratings (p = 0.50). However, by study's end, more men than women had any service connection (88.5% versus 83.5%, p = 0.05), and men's mean total disability rating was substantially greater than women's (77.1 ± 26.2 versus 66.8 ± 30.7, p < 0.001). History of military sexual assault had the largest effect modification on men's versus women's odds of PTSD service connection. CONCLUSION: Even after 2011, cohort men were more likely than the women to reverse initially denied PTSD claims, and military sexual assault history accounted for much of this difference. Service connection for other disorders initially offset women's lower rate of PTSD service connection, but, ultimately, men's total disability ratings exceeded women's. Gender discrepancies in service connection should be monitored beyond the initial claims period.

A Theory of Planned Behavior Scale for Adherence to Trauma-Focused Posttraumatic Stress Disorder Treatments.

Evidence-based psychotherapies for posttraumatic stress disorder (PTSD), such as cognitive processing therapy and prolonged exposure (CPT/PE), greatly reduce suffering for veterans, but many veterans fail to complete treatment. Developing a theory-based understanding of adherence is necessary to inform interventions to improve treatment retention. We developed and tested a series of scales applying the theory of planned behavior (TPB) to CPT/PE adherence. The scales were administered in mailed surveys as part of a larger mixed-methods study of veteran adherence to PE/CPT. Surveys were sent to 379 veterans who were initiating CPT/PE across four U.S. Veterans Affairs (VA) hospitals and 207 of their loved ones. Subsequent session attendance and homework compliance were coded via a review of electronic medical records. We examined item-level characteristics, factor structure, and the convergent and discriminant validity of the resultant scales. The findings support four subscales: two related to attitudes (i.e., Treatment Makes Sense and Treatment Fits Needs), one related to perceived behavioral control over participation (i.e., Participation Control), and one related to perceived family attitudes about CPT/PE participation (i.e., Subjective Norms). Scale validity was supported through significant associations with theoretically relevant constructs, including intentions to persist in CPT/PE, rs = .19-.38; treatment completion, rs = .21-.25; practical treatment barriers, rs = -.19 to -.24; and therapeutic alliance, rs = .39-.57.

Evaluation of an Implementation Intervention to Increase Reach of Evidence-Based Psychotherapies for PTSD in US Veterans Health Administration PTSD Clinics.

To evaluate an implementation intervention to increase the uptake, referred to as reach, of two evidence-based psychotherapies (EBP) for posttraumatic stress disorder (PTSD) in Veterans Health Administration (VHA) PTSD specialty clinics. The implementation intervention was external facilitation guided by a toolkit that bundled strategies associated with high EBP reach in prior research. We used a prospective quasi-experimental design. The facilitator worked with local champions at two low-reach PTSD clinics. Each intervention PTSD clinic was matched to three control clinics. We compared the change in EBP reach from 6-months pre- to post-intervention using Difference-in-Difference (DID) effect estimation. To incorporate possible clustering effects and adjust for imbalanced covariates, we used mixed effects logistic regression to model the probability of EBP receipt. Analyses were conducted separately for PTSD and other mental health clinics. 29,446 veterans diagnosed with PTSD received psychotherapy in the two intervention and six control sites in the two 6-month evaluation periods. The proportion of therapy patients with PTSD receiving an EBP increased by 16.98 percentage points in the intervention PTSD clinics compared with .45 percentage points in the control PTSD clinics (DID = 16.53%; SE = 2.26%). The adjusted odd ratio of a patient receiving an EBP from pre to post intervention was almost three times larger in the intervention than in the control PTSD clinics (RoR 2.90; 95% CI 2.22-3.80). EBP reach was largely unchanged in other (not PTSD specialty) mental health clinics within the same medical centers. Toolkit-guided external facilitation is a promising intervention to improve uptake of EBPs in VHA. Toolkits that pre-specify targets for clinic change based on prior research may enhance the efficiency and effectiveness of external facilitation. Trial registration ISRCTN registry identifier: ISRCTN65119065. Available at https://www.isrctn.com/search?q=ISRCTN65119065 .

Complementary, Integrative, and Nondrug Therapy Use for Pain Among US Military Veterans on Long-term Opioids.

BACKGROUND: Long-term opioid therapy for chronic pain arose amid limited availability and awareness of other pain therapies. Although many complementary and integrative health (CIH) and nondrug therapies are effective for chronic pain, little is known about CIH/nondrug therapy use patterns among people prescribed opioid analgesics. OBJECTIVE: The objective of this study was to estimate patterns and predictors of self-reported CIH/nondrug therapy use for chronic pain within a representative national sample of US military veterans prescribed long-term opioids for chronic pain. RESEARCH DESIGN: National two-stage stratified random sample survey combined with electronic medical record data. Data were analyzed using logistic regressions and latent class analysis. SUBJECTS: US military veterans in Veterans Affairs (VA) primary care who received ≥6 months of opioid analgesics. MEASURES: Self-reported use of each of 10 CIH/nondrug therapies to treat or cope with chronic pain in the past year: meditation/mindfulness, relaxation, psychotherapy, yoga, t'ai chi, aerobic exercise, stretching/strengthening, acupuncture, chiropractic, massage; Brief Pain Inventory-Interference (BPI-I) scale as a measure of pain-related function. RESULTS: In total, 8891 (65%) of 13,660 invitees completed the questionnaire. Eighty percent of veterans reported past-year use of at least 1 nondrug therapy for pain. Younger age and female sex were associated with the use of most nondrug therapies. Higher pain interference was associated with lower use of exercise/movement therapies. Nondrug therapy use patterns reflected functional categories (psychological/behavioral, exercise/movement, manual). CONCLUSIONS: Use of CIH/nondrug therapies for pain was common among patients receiving long-term opioids. Future analyses will examine nondrug therapy use in relation to pain and quality of life outcomes over time.

Effectiveness of Proactive Tobacco Cessation Treatment Outreach Among Smokers With Serious Mental Illness.

INTRODUCTION: People with serious mental illness (SMI) have a high smoking prevalence and low quit rates. Few cessation treatments are tested in smokers with SMI. Mental health (MH) providers are reluctant to address smoking. Proactive tobacco cessation treatment strategies reach out directly to smokers to offer counseling and medication and improve treatment utilization and quit rates. The current study is a secondary analysis of a randomized controlled trial of proactive outreach for tobacco cessation treatment in VA MH patients. AIMS AND METHODS: Participants (N = 1938, 83% male, mean age 55.7) across four recruitment sites, who were current smokers and had a MH visit in the past 12 months, were identified using the electronic medical record. Participants were randomized to Intervention (telephone outreach call plus invitation to engage in MH tailored telephone counseling and assistance obtaining nicotine replacement therapy) or Control (usual care). The current study assessed outcomes in participants with SMI (N = 982). RESULTS: Compared to the Control group, participants assigned to the Intervention group were more likely to engage in telephone counseling (22% vs. 3%) and use nicotine replacement therapy (51% vs. 41%). Participants in the Intervention group were more likely to be abstinent (7-day point prevalence; 18%) at 12 months than participants in the Control group (11%) but equally likely to make quit attempts. CONCLUSIONS: Proactive tobacco cessation treatment is an effective strategy for tobacco users with SMI. Proactive outreach had a particularly strong effect on counseling utilization. Future randomized clinical trials examining proactive tobacco treatment approaches in SMI treatment settings are needed. IMPLICATIONS: Few effective treatment models exist for smokers with SMI. Proactive tobacco cessation outreach with connections to MH tailored telephone counseling and medication promotes tobacco abstinence among smokers with SMI and is an effective treatment strategy for this underserved population.

Sleep Disturbance Predicts Less Improvement in Pain Outcomes: Secondary Analysis of the SPACE Randomized Clinical Trial.

OBJECTIVE: Sleep disturbance may limit improvement in pain outcomes if not directly addressed in treatment. Moreover, sleep problems may be exacerbated by opioid therapy. This study examined the effects of baseline sleep disturbance on improvement in pain outcomes using data from the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial, a pragmatic 12-month randomized trial of opioid vs nonopioid medication therapy. DESIGN: Participants with chronic back pain or hip or knee osteoarthritis pain were randomized to either opioid therapy (N = 120) or nonopioid medication therapy (N = 120). METHODS: We used mixed models for repeated measures to 1) test whether baseline sleep disturbance scores modified the effect of opioid vs nonopioid treatment on pain outcomes and 2) test baseline sleep disturbance scores as a predictor of less improvement in pain outcomes across both treatment groups. RESULTS: The tests for interaction of sleep disturbance by treatment group were not significant. Higher sleep disturbance scores at baseline predicted less improvement in Brief Pain Inventory (BPI) interference (ß = 0.058, P = 0.0002) and BPI severity (ß = 0.026, P = 0.0164). CONCLUSIONS: Baseline sleep disturbance adversely affects pain response to treatment regardless of analgesic regimen. Recognition and treatment of sleep impairments that frequently co-occur with pain may optimize outcomes.

Validating the use of veterans affairs tobacco health factors for assessing change in smoking status: accuracy, availability, and approach.

BACKGROUND: Accurate smoking status is key for research purposes, but can be costly and difficult to measure. Within the Veteran's Health Administration (VA), smoking status is recorded as part of routine care as "health factors" (HF)-fields that researchers can query through the electronic health record (EHR). Many researchers are interested in using these fields to track changes in smoking status over time, however the validity of this measure for assessing change is unknown. The primary goal of this project was to examine whether HFs can be used to accurately measure change in tobacco status over time, with secondary goals of assessing the optimum timeframe for assessment and variation in accuracy by site. METHODS: Secondary analysis of the Veterans VICTORY study, a pragmatic smoking cessation randomized controlled trial conducted from 2009 to 2011. Eligible subjects were identified via the EHR using a past 90-day HF indicating current tobacco use (for example: "CURRENT SMOKER", "CURRENTLY USES TOBACCO"). Participants were surveyed at 1 year to determine prolonged smoking abstinence. We identified HFs for tobacco status within +/- 120 days of the follow-up survey mailing date and recorded the temporally closest HF. Among subjects with both measures, we compared the two for agreement using kappa statistics and concordance. RESULTS: 1713 subjects (33%) had both follow-up survey and HF data, 1594 (31%) had only a survey response, 790 (15%) had only HF and 1026 (20%) had neither. For subjects with both measures, there was 90% concordance and moderate agreement (Kappa 0.48, 95%CI 0.41-0.55, Sensitivity 54.4, 95%CI 41.1-67.7, Specificity 94.3, 95%CI 87.5-100.0). CONCLUSIONS: We found high concordance but only moderate agreement by kappa statistics between HFs and survey data. The difference is likely accounted for by the natural history of quit attempts, in which patients cycle in and out of quit attempts. HFs appear to provide an accurate measure of population level quit behavior utilizing data collected in the course of clinical care.

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial.

Importance: Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain. Objective: To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects. Design, Setting, and Participants: Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized. Interventions: Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response. Main Outcomes and Measures: The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19). Results: Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, -0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]). Conclusions and Relevance: Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain. Trial Registration: clinicaltrials.gov Identifier: NCT01583985.

Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

BACKGROUND: There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA). METHODS: Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student's t-tests and Spearman's correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0-10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale. RESULTS: In a pilot study, compared to non-responders (n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection (p < 0.05 for all). Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging -0.37 to -0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders (0.54 ± 0.53; n = 10) than in the pain non-responders (0.48 ± 1.18; n = 9; p = 0.023) and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 (p = 0.021; n = 19). Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population. CONCLUSION: Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial.

Does Motivation Matter? Analysis of a Randomized Trial of Proactive Outreach to VA Smokers.

BACKGROUND: Current guidelines advise providers to assess smokers' readiness to quit, then offer cessation therapies to smokers planning to quit and motivational interventions to smokers not planning to quit. OBJECTIVES: We examined the relationship between baseline stage of change (SOC), treatment utilization, and smoking cessation to determine whether the effect of a proactive smoking cessation intervention was dependent on smokers' level of motivation to quit. DESIGN: Secondary analysis of a multicenter randomized controlled trial. PARTICIPANTS: A total of 3006 current smokers, aged 18-80 years, at four Veterans Affairs (VA) medical centers. INTERVENTIONS: Proactive care included proactive outreach (mailed invitation followed by telephone outreach), offer of smoking cessation services (telephone or face-to-face), and access to pharmacotherapy. Usual care participants had access to VA smoking cessation services and state telephone quitlines. MAIN MEASURES: Baseline SOC measured with Readiness to Quit Ladder, and 6-month prolonged abstinence self-reported at 1 year. KEY RESULTS: At baseline, 35.8 % of smokers were in preparation, 38.2 % in contemplation, and 26.0 % in precontemplation. The overall interaction between SOC and treatment arm was not statistically significant (p = 0.30). Among smokers in preparation, 21.1 % of proactive care participants achieved 6-month prolonged abstinence, compared to 13.1 % of usual care participants (OR, 1.8 [95 % CI, 1.2-2.6]). Similarly, proactive care increased abstinence among smokers in contemplation (11.0 % vs. 6.5 %; OR, 1.8 [95 % CI, 1.1-2.8]). Smokers in precontemplation quit smoking at similar rates (5.3 % vs. 5.6 %; OR, 0.9 [95 % CI, 0.5-1.9]). Within each stage, uptake of smoking cessation treatments increased with higher SOC and with proactive care as compared with usual care. LIMITATIONS: Mostly male participants limits generalizability. Randomization was not stratified by SOC. CONCLUSIONS: Proactive care increased treatment uptake compared to usual care across all SOC. Proactive care increased smoking cessation among smokers in preparation and contemplation but not in precontemplation. Proactively offering cessation therapies to smokers at all SOC will increase treatment utilization and population-level smoking cessation.

Increasing comorbidity is associated with worsening physical function and pain after primary total knee arthroplasty.

BACKGROUND: Previous studies suggested that pre-operative comorbidity was a risk factor for worse outcomes after TKA. To our knowledge, studies have not examined whether postoperative changes in comorbidity impact pain and function outcomes longitudinally. Our objective was to examine if increasing comorbidity postoperatively is associated with worsening physical function and pain after primary total knee arthroplasty (TKA). METHODS: We performed a retrospective chart review of veterans who had completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF36) surveys at regular intervals after primary TKA. Comorbidity was assessed using a variety of scales: validated Charlson comorbidity index score, and a novel Arthroplasty Comorbidity Severity Index score (Including medical index, local musculoskeletal index [including lower extremity and spine] and TKA-related index subscales; higher scores are worse ), at multiple time-points post-TKA. We used mixed model linear regression to examine the association of worsening comorbidity post-TKA with change in WOMAC and SF-36 scores in the subsequent follow-up periods, controlling for age, length of follow-up, and repeated observations. RESULTS: The study cohort consisted of 124 patients with a mean age of 71.7 years (range 58.6-89.2, standard deviation (SD) 6.9) followed for a mean of 4.9 years post-operatively (range 1.3-11.4; SD 2.8). We found that post-operative worsening of the Charlson Index score was significantly associated with worsening SF-36 Physical Function (PF) (beta coefficient (ß) = -0.07; p < 0.0001), SF-36 Bodily Pain (BP) (ß = -0.06; p = 0.002), and WOMAC PF subscale (ß = 0.08; p < 0.001; higher scores are worse) scores, in the subsequent periods. Worsening novel medical index subscale scores were significantly associated with worsening SF-36 PF scores (ß = -0.03; p = 0.002), SF-36 BP (ß = -0.04; p < 0.001) and showed a non-significant trend for worse WOMAC PF scores (ß = 0.02; p = 0.11) subsequently. Local musculoskeletal index subscale scores were significantly associated with worsening SF-36 PF (ß = -0.05; p = 0.001), SF-36 BP (ß = -0.04; p = 0.03) and WOMAC PF (ß = 0.06; p = 0.01) subsequently. None of the novel index subscale scores were significantly associated with WOMAC pain scores. TKA complications, as assessed by TKA-related index subscale,  were not significantly associated with SF-36 or WOMAC domain scores. CONCLUSIONS: Increasing Charlson index as well as novel medical and local musculoskeletal index subscale scores (from novel Arthroplasty  Comorbidity Severity Index) post-TKA correlated with subsequent worsening of physical function and pain outcomes post-TKA. Further studies should examine which comorbidity management could have the greatest impact on these outcomes.

Rates and correlates of potentially inappropriate colorectal cancer screening in the Veterans Health Administration.

BACKGROUND: Inappropriate use of colorectal cancer (CRC) screening procedures can inflate healthcare costs and increase medical risk. Little is known about the prevalence or causes of inappropriate CRC screening. OBJECTIVE: Our aim was to estimate the prevalence of potentially inappropriate CRC screening, and its association with patient and facility characteristics in the Veterans Health Administration (VHA) . DESIGN AND PARTICIPANTS: We conducted a cross-sectional study of all VHA patients aged 50 years and older who completed a fecal occult blood test (FOBT) or a screening colonoscopy between 1 October 2009 and 31 December 2011 (n = 1,083,965). MAIN MEASURES: Measures included: proportion of patients whose test was classified as potentially inappropriate; associations between potentially inappropriate screening and patient demographic and health characteristics, facility complexity, CRC screening rates, dependence on FOBT, and CRC clinical reminder attributes. KEY RESULTS: Of 901,292 FOBT cases, 26.1 % were potentially inappropriate (13.9 % not due, 7.8 % limited life expectancy, 11.0 % receiving FOBT when colonoscopy was indicated). Of 134,335 screening colonoscopies, 14.2 % were potentially inappropriate (10.4 % not due, 4.4 % limited life expectancy). Each additional 10 years of patient age was associated with an increased likelihood of undergoing potentially inappropriate screening (ORs = 1.60 to 1.83 depending on screening mode). Compared to facilities scoring in the bottom third on a measure of reliance on FOBT (versus screening colonoscopy), facilities scoring in the top third were less likely to conduct potentially inappropriate FOBTs (OR = 0.,78) but more likely to conduct potentially inappropriate colonoscopies (OR = 2.20). Potentially inappropriate colonoscopies were less likely to be conducted at facilities where primary care providers were assigned partial responsibility (OR = 0.74) or full responsibility (OR = 0.73) for completing the CRC clinical reminder. CONCLUSIONS: A substantial number of VHA CRC screening tests are potentially inappropriate. Establishing processes that enforce appropriate screening intervals, triage patients with limited life expectancies, and discourage the use of FOBTs when a colonoscopy is indicated may reduce inappropriate testing.

Randomized Controlled Trial of Online Expressive Writing to Address Readjustment Difficulties Among U.S. Afghanistan and Iraq War Veterans.

We examined the efficacy of a brief, accessible, nonstigmatizing online intervention-writing expressively about transitioning to civilian life. U.S. Afghanistan and Iraq war veterans with self-reported reintegration difficulty (N = 1,292, 39.3% female, M = 36.87, SD = 9.78 years) were randomly assigned to expressive writing (n = 508), factual control writing (n = 507), or no writing (n = 277). Using intention to treat, generalized linear mixed models demonstrated that 6-months postintervention, veterans who wrote expressively experienced greater reductions in physical complaints, anger, and distress compared with veterans who wrote factually (ds = 0.13 to 0.20; ps < .05) and greater reductions in PTSD symptoms, distress, anger, physical complaints, and reintegration difficulty compared with veterans who did not write at all (ds = 0.22 to 0.35; ps ≤ .001). Veterans who wrote expressively also experienced greater improvement in social support compared to those who did not write (d = 0.17). Relative to both control conditions, expressive writing did not lead to improved life satisfaction. Secondary analyses also found beneficial effects of expressive writing on clinically significant distress, PTSD screening, and employment status. Online expressive writing holds promise for improving health and functioning among veterans experiencing reintegration difficulty, albeit with small effect sizes.

Iraq and Afghanistan War Veterans with Reintegration Problems: Differences by Veterans Affairs Healthcare User Status.

We studied 1,292 Iraq and Afghanistan War veterans who participated in a clinical trial of expressive writing to estimate the prevalence of perceived reintegration difficulty and compare Veterans Affairs (VA) healthcare users to nonusers in terms of demographic and clinical characteristics. About half of participants perceived reintegration difficulty. VA users and nonusers differed in age and military background. Levels of mental and physical problems were higher in VA users. In multivariate analysis, military service variables and probable traumatic brain injury independently predicted VA use. Findings demonstrate the importance of research comparing VA users to nonusers to understand veteran healthcare needs.

Smoking cessation among African American and white smokers in the Veterans Affairs health care system.

OBJECTIVES: We examined whether a proactive care smoking cessation intervention designed to overcome barriers to treatment would be especially effective at increasing cessation among African Americans receiving care in the Veterans Health Administration. METHODS: We analyzed data from a randomized controlled trial, the Veterans Victory over Tobacco study, involving a population-based electronic registry of current smokers (702 African Americans, 1569 whites) and assessed 6-month prolonged smoking abstinence at 1 year via a follow-up survey of all current smokers. We also examined candidate risk adjustors for the race effect on smoking abstinence. RESULTS: The interaction between patient race and intervention condition (proactive care vs. usual care) was not significant. Overall, African Americans had higher quit rates than Whites (13% vs. 9%; P < .006) regardless of condition. CONCLUSIONS: African Americans quit at higher rates than Whites. These findings may be a result of the large number of veterans receiving smoking cessation services and the lack of racial differences in receipt of these services as well as racial differences in smoking history, self-efficacy, and motivation to quit that favor African Americans.