Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.

INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.

Association Between Opioid Dose Reduction Against Patients' Wishes and Change in Pain Severity.

BACKGROUND: There is inadequate evidence of long-term benefit from opioid medications for chronic pain and substantial evidence of potential harms. For patients, dose reduction may be beneficial when implemented voluntarily and supported by a multidisciplinary team but experts have advised against involuntary opioid reduction. OBJECTIVES: To assess the prevalence of self-reported involuntary opioid reduction and to examine whether involuntary opioid reduction is associated with changes in pain severity. DESIGN: Prospective observational cohort study. PARTICIPANTS: Primary care patients treated with long-term opioid therapy in the Veterans Health Administration (N = 290). MAIN MEASURES: The primary exposure was self-reported past year involuntary opioid reduction. The primary outcome was the three-item PEG scale, which measures past-week average pain intensity and interference with enjoyment of life and general activity. KEY RESULTS: Past year opioid reduction or discontinuation was reported by 63% (184/290). Similar numbers reported involuntary (88/290) and voluntary (96/290) opioid reduction. At baseline, there were no significant differences in pain severity between the groups (mean PEG, 7.08 vs. 6.73 vs. 7.07 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.32). For the primary outcome of change in pain severity from baseline to 18 months, there were no significant differences between groups (mean PEG change, - 0.05 vs. - 0.44 vs. - 0.23 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.28). CONCLUSIONS: Self-reported past year involuntary opioid reduction was common among a national sample of veterans treated with long-term opioid therapy. Opioid dose reduction, whether involuntary or voluntary, was not associated with change in pain severity. Future studies should examine involuntary opioid reduction in different populations and trends over time and explore further patient- and provider-level factors that may impact patient experience and outcomes during opioid reduction.

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.

Contribution of patient, physician, and environmental factors to demographic and health variation in colonoscopy follow-up for abnormal colorectal cancer screening test results.

BACKGROUND: Patient, physician, and environmental factors were identified, and the authors examined the contribution of these factors to demographic and health variation in colonoscopy follow-up after a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT-positive patients were identified from 120 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011 and were followed for 6 months. Patient demographic (race/ethnicity, sex, age, marital status) and health characteristics (comorbidities), physician characteristics (training level, whether primary care provider) and behaviors (inappropriate FOBT/FIT screening), and environmental factors (geographic access, facility type) were identified from VHA administrative records. Patient behaviors (refusal, private sector colonoscopy use) were estimated with statistical text mining conducted on clinic notes, and follow-up predictors and adjusted rates were estimated using hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a colonoscopy at a VHA facility within 6 months. Age and comorbidity score were negatively associated with follow-up. Blacks were more likely to receive follow-up than whites. Environmental factors attenuated but did not fully account for these differences. Patient behaviors (refusal, private sector colonoscopy use) and physician behaviors (inappropriate screening) fully accounted for the small reverse race disparity and attenuated variation by age and comorbidity score. Patient behaviors (refusal and private sector colonoscopy use) contributed more to variation in follow-up rates than physician behaviors (inappropriate screening). CONCLUSIONS: In the VHA, blacks are more likely to receive colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up rates markedly decline with advancing age and comorbidity burden. Patient and physician behaviors explain race variation in follow-up rates and contribute to variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017. This article is a US Government work and is in the public domain in the USA.

Factors Associated With Missed and Cancelled Colonoscopy Appointments at Veterans Health Administration Facilities.

BACKGROUND & AIMS: Cancelled and missed colonoscopy appointments waste resources, increase colonoscopy delays, and can adversely affect patient outcomes. We examined individual and organizational factors associated with missed and cancelled colonoscopy appointments in Veteran Health Administration facilities. METHODS: From 69 facilities meeting inclusion criteria, we identified 27,994 patients with colonoscopy appointments scheduled for follow-up, on the basis of positive fecal occult blood test results, between August 16, 2009 and September 30, 2011. We identified factors associated with colonoscopy appointment status (completed, cancelled, or missed) by using hierarchical multinomial regression. Individual factors examined included age, race, sex, marital status, residence, drive time to nearest specialty care facility, limited life expectancy, comorbidities, colonoscopy in the past decade, referring facility type, referral month, and appointment lead time. Organizational factors included facility region, complexity, appointment reminders, scheduling, and prep education practices. RESULTS: Missed appointments were associated with limited life expectancy (odds ratio [OR], 2.74; P = .0004), no personal history of polyps (OR, 2.74; P < .0001), high facility complexity (OR, 2.69; P = .007), dual diagnosis of psychiatric disorders and substance abuse (OR, 1.82; P < .0001), and opt-out scheduling (OR, 1.57; P = .02). Cancelled appointments were associated with age (OR, 1.61; P = .0005 for 85 years or older and OR, 1.44; P < .0001 for 65-84 years old), no history of polyps (OR, 1.51; P < .0001), and opt-out scheduling (OR, 1.26; P = .04). Additional predictors of both outcomes included race, marital status, and lead time. CONCLUSIONS: Several factors within Veterans Health Administration clinic control can be targeted to reduce missed and cancelled colonoscopy appointments. Specifically, developing systems to minimize referrals for patients with limited life expectancy could reduce missed appointments, and use of opt-in scheduling and reductions in appointment lead time could improve both outcomes.

Telehealth by an Interprofessional Team in Patients With CKD: A Randomized Controlled Trial.

BACKGROUND: Telehealth and interprofessional case management are newer strategies of care within chronic disease management. We investigated whether an interprofessional team using telehealth was a feasible care delivery strategy and whether this strategy could affect health outcomes in patients with chronic kidney disease (CKD). STUDY DESIGN: Randomized clinical trial. SETTING & PARTICIPANTS: Minneapolis Veterans Affairs Health Care System (VAHCS), St. Cloud VAHCS, and affiliated clinics March 2012 to November 2013 in patients with CKD (estimated glomerular filtration rate < 60mL/min/1.73m(2)). INTERVENTIONS: Patients were randomly assigned to receive an intervention (n=451) consisting of care by an interprofessional team (nephrologist, nurse practitioner, nurses, clinical pharmacy specialist, psychologist, social worker, and dietician) using a telehealth device (touch screen computer with peripherals) or to usual care (n=150). OUTCOMES: The primary end point was a composite of death, hospitalization, emergency department visits, or admission to skilled nursing facilities, compared to usual care. RESULTS: Baseline characteristics of the overall study group: mean age, 75.1±8.1 (SD) years; men, 98.5%; white, 97.3%; and mean estimated glomerular filtration rate, 37±9mL/min/1.73m(2). Telehealth and interprofessional care were successfully implemented with meaningful engagement with the care system. One year after randomization, 208 (46.2%) patients in the intervention group versus 70 (46.7%) in the usual-care group had the primary composite outcome (HR, 0.98; 95% CI, 0.75-1.29; P=0.9). There was no difference between groups for any component of the primary outcome: all-cause mortality (HR, 1.46; 95% CI, 0.42-5.11), hospitalization (HR, 1.15; 95% CI, 0.80-1.63), emergency department visits (HR, 0.92; 95% CI, 0.68-1.24), or nursing home admission (HR, 3.07; 95% CI, 0.71-13.24). LIMITATIONS: Older population, mostly men, potentially underpowered/wide CIs. CONCLUSIONS: Telehealth by an interprofessional team is a feasible care delivery strategy in patients with CKD. There was no statistically significant evidence of superiority of this intervention on health outcomes compared to usual care.

Are there racial/ethnic disparities in VA PTSD treatment retention?

BACKGROUND: Chronic posttraumatic stress disorder (PTSD) can result in significant social and physical impairments. Despite the Department of Veterans Affairs' (VA) expansion of mental health services into primary care clinics to reach larger numbers of Veterans with PTSD, many do not receive sufficient treatment to clinically benefit. This study explored whether the odds of premature mental health treatment termination varies by patient race/ethnicity and, if so, whether such variation is associated with differential access to services or beliefs about mental health treatments. METHODS: Prospective national cohort study of VA patients who were recently diagnosed with PTSD (n = 6,788). Self-administered surveys and electronic VA databases were utilized to examine mental health treatment retention across racial/ethnic groups in the 6 months following the PTSD diagnosis controlling for treatment need, access factors, age, gender, treatment beliefs, and facility factors. RESULTS: African American and Latino Veterans were less likely to receive a minimal trial of pharmacotherapy and African American Veterans were less likely to receive a minimal trial of any treatment in the 6 months after being diagnosed with PTSD. Controlling for beliefs about mental health treatments diminished the lower odds of pharmacotherapy retention among Latino but not African American Veterans. Access factors did not contribute to treatment retention disparities. CONCLUSIONS: Even in safety-net healthcare systems like VA, racial and ethnic disparities in mental health treatment occur. To improve treatment equity, clinicians may need to more directly address patients' treatment beliefs. More understanding is needed to address the treatment disparity for African American Veterans.

Acute Beetroot Juice Supplementation Does Not Improve Cycling Performance in Normoxia or Moderate Hypoxia.

Beetroot juice (BR) has been shown to lower the oxygen cost of exercise in normoxia and may have similar effects in hypoxia. We investigated the effect of BR on steady-state exercise economy and 10-km time trial (TT) performance in normoxia and moderate hypoxia (simulated altitude: ~2500 m). Eleven trained male cyclists (VO 2peak ≥ 60 ml · kg(-1) · min(-1)) completed four exercise trials. Two hours before exercise, subjects consumed 70 mL BR (~6 mmol nitrate) or placebo (nitrate-depleted BR) in a randomized, double-blind manner. Subjects then completed a 15-min self-selected cycling warm-up, a 15-min steady-state exercise bout at 50% maximum power output, and a 10-km time trial (TT) in either normoxia or hypoxia. Environmental conditions were randomized and single-blind. BR supplementation increased plasma nitrate concentration and fraction of exhaled nitric oxide relative to PL (p < .05 for both comparisons). Economy at 50% power output was similar in hypoxic and normoxic conditions (p > .05), but mean power output was greater in the normoxic TT relative to the hypoxic TT (p < .05). BR did not affect economy, steady-state SpO2, mean power output, or 10-km TT completion time relative to placebo in either normoxia or hypoxia (p > .05 in all comparisons). In conclusion, BR did not lower the oxygen cost of steady-state exercise or improve exercise performance in normoxia or hypoxia in a small sample of well-trained male cyclists.

Proactive outreach for smokers using VHA mental health clinics: protocol for a patient-randomized clinical trial.

BACKGROUND: Persons with a mental health diagnosis have high rates of tobacco use and face numerous barriers to cessation including high levels of nicotine dependence, low rates of tobacco treatment referrals from mental health providers, and limited availability of tobacco treatment targeted to their needs. This manuscript describes the rationale and methods of a clinical trial with the following aims: 1) Compare the reach and efficacy of a proactive telephone-based tobacco cessation program for Veterans Health Administration (VHA) mental health clinic patients to VHA usual care and 2) Model longitudinal associations between baseline patient characteristics and long-term abstinence. METHODS/DESIGN: We will use the electronic medical record to identify patients across four VHA healthcare facilities who have a clinical reminder code indicating current tobacco use in the past six months and who have had a mental health clinic visit in the past 12 months. We will send each patient an introductory letter and baseline survey. Survey respondents (N = 3840) will be randomized in a 1:1 fashion to intervention or control. Control participants will receive VHA usual care. Intervention participants will receive proactive motivational telephone outreach to offer tobacco treatment. Intervention participants interested in treatment will receive eight weeks of nicotine replacement therapy plus eight sessions of specialized telephone counseling over two months, followed by monthly maintenance counseling for four months. We will conduct telephone surveys with participants at six and 12 months to assess study outcomes. We will collect a mailed saliva sample from patients reporting 7-day abstinence on the telephone surveys. The primary outcome will be cotinine-validated abstinence at 12-month follow-up. DISCUSSION: Mental health patients are a high-risk smoking population with significant barriers to cessation. This study will evaluate the efficacy of a program that proactively reaches out to smokers with a mental health treatment history to engage them into telephone cessation counseling targeted to the needs of mental health patients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01737281 (registered November 5, 2012).

The second Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland.

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Rates and reasons for veteran mental health service utilization following completion of evidence-based trauma-focused treatment for PTSD.

Despite the effectiveness of prolonged exposure (PE) and cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) in reducing symptoms of PTSD and co-occurring symptoms, emerging research suggests continued mental health service utilization (MHSU) following the completion of these interventions. Reasons for continued MHSU remain unknown despite its relevance to PE/CPT outcomes and implementation. The present study employed a mixed methods approach to explore rates and reasons for VA MHSU post PE/CPT. A national sample of 5,634 U.S. veterans who completed either PE or CPT were identified to quantitatively determine the frequency, type, and location of MHSU in the 12 months following PE/CPT completion. A random subsample of 60 veterans completed semistructured qualitative interviews to explore reasons for MHSU post PE/CPT. Findings suggest high MHSU; 98.4% of veterans attended at least one mental health appointment in the year following completion of PE/CPT, with an average attending 27.64 appointments in the year following treatment completion. Qualitatively, veterans, particularly those with low-to-moderate residual symptoms, described a preference for additional treatment to continue practicing and applying skills learned in treatment. Veterans expressed low self-efficacy to maintain treatment gains without support and accountability from their therapists and viewed ongoing treatment as a safety net until they felt more confident in their skills and stability of gains. Veterans with high residual symptoms indicated needing additional PTSD-specific treatment or treatment for a co-occurring condition. Notably, some veterans reported no additional treatment needs, despite continued engagement in care. Evidence-based strategies for facilitating self-efficacy and ongoing application of PE/CPT principles posttreatment are needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Design, methods, and recruitment outcomes of the Veterans' Pain Care Organizational Improvement Comparative Effectiveness (VOICE) study.

The Veterans' Pain Care Organizational Improvement Comparative Effectiveness (VOICE) study is a 12-month pragmatic randomized comparative effectiveness trial conducted at ten United States Veterans Affairs (VA) health care sites. The overall goal was to test interventions to improve pain while reducing opioid use among VA patients with moderate-severe chronic pain despite treatment with long-term opioid therapy (LTOT). Aims were 1) to compare lower-intensity telecare collaborative pain management (TCM) versus higher-intensity integrated pain team management (IPT), and 2) to test the option of switching to buprenorphine (versus no option) in a high-dose subgroup. Recruitment challenges included secular trends in opioid prescribing and the COVID-19 pandemic. Participants were recruited over 3.5 years. Of 6966 potentially eligible patients, 4731 (67.9%) were contacted for telephone eligibility interview; of those contacted, 3398 (71.8%) declined participation, 359 (7.6%) were ineligible, 821 (24.2%) enrolled, and 820 (24.1%) were randomized. The most common reason for declining was satisfaction with pain care (n = 731). The most common reason for ineligibility was not having moderate-severe chronic pain (n = 110). Compared with the potentially eligible population, randomized participants were slightly younger, more often female, had similar prescribed opioids, and had similar or higher rates of pain and mental health diagnoses. The enrolled patient number was lower than the original target, but sufficient to power planned analyses. In conclusion, the VOICE trial enrolled a diverse sample similar to the population of VA patients receiving LTOT. Results will add substantially to limited existing evidence for interventions to improve pain while reducing opioid use. ClinicalTrials.gov identifier: NCT03026790.

Evaluation of a VHA collaborative to improve follow-up after a positive colorectal cancer screening test.

BACKGROUND: In 2005, the Veterans Health Administration initiated a yearlong Colorectal Cancer Care Collaborative (C4) to improve timely follow-up after positive fecal occult blood tests. METHODS: Twenty-one facilities formed local quality improvement (QI) teams. Teams received QI training, created process flow maps, implemented process changes, and shared learning through 2 face-to-face meetings, conference calls, and a discussion board. We evaluated pre-post change in the timeliness of follow-up among C4 facilities and 3 control facilities. Outcome measures included the proportion of patients receiving a follow-up colonoscopy within 1 year, the proportion receiving 60-day follow-up (the focus of C4 teams), and average days to colonoscopy. Survey data from C4 team members was analyzed to identify predictors of facility-level improvement. RESULTS: Both C4 and control facilities improved on 1-year follow-up (10% and 9% increases, respectively, both P's<0.001). There was a statistically significant increase in the proportion receiving 60-day follow-up among C4 facilities (27% pre-C4 vs. 39% post-C4, P=0.008) but a nonsignificant decrease among control facilities (45% pre-C4 vs. 29% post-C4, P=0.14). Average days to colonoscopy decreased significantly among C4 facilities (129 pre-C4 vs. 103 post-C4, P=0.004) but increased significantly among control facilities (81 pre-C4 vs. 103 post-C4, P=0.04). Teams with the most improvement established clear roles/goals, had previous QI training, made more use of QI tools, and incorporated primary care education into their improvement work. CONCLUSIONS: A Veterans Health Administration improvement collaborative modestly decreased time to colonoscopy after a positive colorectal cancer screening test but significant room for improvement remains and benefits of participation were not realized by all facilities.

Evaluation of the Veterans Health Administration traumatic brain injury screening program in the upper Midwest.

OBJECTIVE: To evaluate the Veterans Health Administration's traumatic brain injury (TBI) screening program in terms of predictors of screening and positive-screen follow-up. DESIGN: Retrospective administrative data study. Multiple logistic regression analyses were used to estimate the odds of TBI screening at a given appointment and among those screening positive, follow-up in a TBI/polytrauma specialty clinic. PARTICIPANTS: A total of 15,973 Iraq and Afghanistan war veterans treated at a Veterans Affairs medical center in the upper Midwest during the first 18 months of the TBI screening program. RESULTS: Almost 90% of Iraq and Afghanistan veteran patients were offered TBI screening and 17% screened positive. Screening rates increased over time and varied by facility. Appointment type predicted screening with increased likelihood of screening during primary care and TBI/polytrauma clinic appointments. Younger, male, and army veterans without psychiatric diagnoses were more likely to be screened. Fifty-two percent of positive TBI screens had subsequent appointments in a TBI/polytrauma specialty clinic during the study period. Rates of follow-up in the clinic increased over time and varied by facility and patient characteristics. CONCLUSIONS: Within the upper Midwest, Veterans Health Administration has had greater success implementing TBI screening than ensuring follow-up of positive screens in a specialty clinic. Research is needed on barriers to follow-up of positive screens and the outcomes of TBI screening and subsequent specialty care.

Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies.

The Huggins coefficient kH is a well-known metric for quantifying the increase in solution viscosity arising from intermolecular interactions in relatively dilute macromolecular solutions, and there has been much interest in this solution property in connection with developing improved antibody therapeutics. While numerous kH measurements have been reported for select monoclonal antibodies (mAbs) solutions, there has been limited study of kH in terms of the fundamental molecular interactions that determine this property. In this paper, we compare measurements of the osmotic second virial coefficient B22, a common metric of intermolecular and interparticle interaction strength, to measurements of kH for model antibody solutions. This comparison is motivated by the seminal work of Russel for hard sphere particles having a short-range "sticky" interparticle interaction, and we also compare our data with known results for uncharged flexible polymers having variable excluded volume interactions because proteins are polypeptide chains. Our observations indicate that neither the adhesive hard sphere model, a common colloidal model of globular proteins, nor the familiar uncharged flexible polymer model, an excellent model of intrinsically disordered proteins, describes the dependence of kH of these antibodies on B22. Clearly, an improved understanding of protein and ion solvation by water as well as dipole-dipole and charge-dipole effects is required to understand the significance of kH from the standpoint of fundamental protein-protein interactions. Despite shortcomings in our theoretical understanding of kH for antibody solutions, this quantity provides a useful practical measure of the strength of interprotein interactions at elevated protein concentrations that is of direct significance for the development of antibody formulations that minimize the solution viscosity.

Variation in estimates of limited health literacy by assessment instruments and non-response bias.

OBJECTIVES: This paper compares estimates of poor health literacy using two widely used assessment tools and assesses the effect of non-response on these estimates. STUDY DESIGN AND SETTING: A total of 4,868 veterans receiving care at four VA medical facilities between 2004 and 2005 were stratified by age and facility and randomly selected for recruitment. Interviewers collected demographic information and conducted assessments of health literacy (both REALM and S-TOFHLA) from 1,796 participants. Prevalence estimates for each assessment were computed. Non-respondents received a brief proxy questionnaire with demographic and self-report literacy questions to assess non-response bias. Available administrative data for non-participants were also used to assess non-response bias. RESULTS: Among the 1,796 patients assessed using the S-TOFHLA, 8% had inadequate and 7% had marginal skills. For the REALM, 4% were categorized with 6th grade skills and 17% with 7-8th grade skills. Adjusting for non-response bias increased the S-TOFHLA prevalence estimates for inadequate and marginal skills to 9.3% and 11.8%, respectively, and the REALM estimates for < or = 6th and 7-8th grade skills to 5.4% and 33.8%, respectively. CONCLUSIONS: Estimates of poor health literacy varied by the assessment used, especially after adjusting for non-response bias. Researchers and clinicians should consider the possible limitations of each assessment when considering the most suitable tool for their purposes.

Psychiatric diagnoses among Iraq and Afghanistan war veterans screened for deployment-related traumatic brain injury.

The authors examined psychiatric diagnoses in administrative records for 13,201 United States military veterans who were screened for traumatic brain injury (TBI) in Department of Veterans Affairs facilities. Over 80% of the veterans with positive TBI screens had psychiatric diagnoses. Compared to veterans with negative TBI screens, those with positive screens, but without confirmed TBI status, were three times more likely to have a posttraumatic stress disorder (PTSD) diagnosis and were two times more likely to have depression and substance-related diagnoses. Among veterans with positive TBI screens, those with clinically confirmed TBI status were more likely than those without confirmed TBI status to have diagnoses for PTSD, anxiety, and adjustment disorders. These findings have implications for health care delivery and provider education.

Impact of age and comorbidity on colorectal cancer screening among older veterans.

BACKGROUND: The Veterans Health Administration, the American Cancer Society, and the American Geriatrics Society recommend colorectal cancer screening for older adults unless they are unlikely to live 5 years or have significant comorbidity that would preclude treatment. OBJECTIVE: To determine whether colorectal cancer screening is targeted to healthy older patients and is avoided in older patients with severe comorbidity who have life expectancies of 5 years or less. DESIGN: Cohort study. SETTING: Veterans Affairs (VA) medical centers in Minneapolis, Minnesota; Durham, North Carolina; Portland, Oregon; and West Los Angeles, California, with linked national VA and Medicare administrative claims. PATIENTS: 27 068 patients 70 years or older who had an outpatient visit at 1 of 4 VA medical centers in 2001 or 2002 and were due for screening. MEASUREMENTS: The main outcome was receipt of fecal occult blood testing (FOBT), colonoscopy, sigmoidoscopy, or barium enema in 2001 or 2002, on the basis of national VA and Medicare claims. Charlson-Deyo comorbidity scores at the start of 2001 were used to stratify patients into 3 groups ranging from no comorbidity (score of 0) to severe comorbidity (score > or =4), and 5-year mortality was determined for each group. RESULTS: 46% of patients were screened from 2001 through 2002. Only 47% of patients with no comorbidity were screened despite having life expectancies greater than 5 years (5-year mortality, 19%). Although the incidence of screening decreased with age and worsening comorbidity, it was still 41% for patients with severe comorbidity who had life expectancies less than 5 years (5-year mortality, 55%). The number of VA outpatient visits predicted screening independent of comorbidity, such that patients with severe comorbidity and 4 or more visits had screening rates similar to or higher than those of healthier patients with fewer visits. LIMITATIONS: Some tests may have been performed for nonscreening reasons. The generalizability of findings to persons who do not use the VA system is uncertain. CONCLUSION: Advancing age was inversely associated with colorectal cancer screening, whereas comorbidity was a weaker predictor. More attention to comorbidity is needed to better target screening to older patients with substantial life expectancies and avoid screening older patients with limited life expectancies. primary funding source: VA Health Services Research and Development.

The evaluating prescription opioid changes in veterans (EPOCH) study: Design, survey response, and baseline characteristics.

In the United States (US), long-term opioid therapy has been commonly prescribed for chronic pain. Since recognition of the opioid overdose epidemic, clinical practice guidelines have recommended tapering long-term opioids to reduced doses or discontinuation. The Effects of Prescription Opioid Changes for veterans (EPOCH) study is a national population-based prospective observational study of US Veterans Health Administration primary care patients designed to assess effects of evolving opioid prescribing practice on patients treated with long-term opioids for chronic pain. A stratified random sampling design was used to identify a survey sample from the target population of patients treated with opioid analgesics for ≥ 6 months. Demographic, diagnostic, visit, and pharmacy dispensing data were extracted from existing datasets. A 2016 mixed-mode mail and telephone survey collected patient-reported data, including the main patient-reported outcomes of pain-related function (Brief Pain Inventory interference; BPI-I scores 0-10, higher scores = worse) and health-related quality of life. Data on survey participants and non-participants were analyzed to assess potential nonresponse bias. Weights were used to account for design. Linear regression models were used to assess cross-sectional associations of opioid treatment with patient-reported measures. Of 14,160 patients contacted, 9253 (65.4%) completed the survey. Participants were older than non-participants (63.9 ± 10.6 vs. 59.6 ± 13.0 years). The mean number of bothersome pain locations was 6.8 (SE 0.04). Effectiveness of pain treatment and quality of pain care were rated fair or poor by 56.1% and 45.3%, respectively. The opioid daily dosage range was 1.6 to 1038.2 mg, with mean = 50.6 mg (SE 1.1) and median = 30.9 mg (IQR 40.7). Among the 73.2% of patients who did not receive long-acting opioids, the mean daily dosage was 30.4 mg (SE 0.6) and mean BPI-I was 6.4 (SE 00.4). Among patients who received long-acting opioids, the mean daily dosage was 106.2 mg (SE 2.8) and mean BPI-I was 6.8 (SE 0.07). Higher daily dosage was associated with worse pain-related function and quality of life among patients without long-acting opioids, but not among patients with long-acting opioids. Future analyses will use follow-up data to examine effects of opioid dose reduction and discontinuation on patient outcomes.