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.

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.

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.

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.

Structure-Based Design of Nipah Virus Vaccines: A Generalizable Approach to Paramyxovirus Immunogen Development.

Licensed vaccines or therapeutics are rarely available for pathogens with epidemic or pandemic potential. Developing interventions for specific pathogens and defining generalizable approaches for related pathogens is a global priority and inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses a significant epidemic threat, and zoonotic transmission from bats-to-humans with high fatality rates occurs almost annually. Human-to-human transmission of NiV has been documented in recent outbreaks leading public health officials and government agencies to declare an urgent need for effective vaccines and therapeutics. Here, we evaluate NiV vaccine antigen design options including the fusion glycoprotein (F) and the major attachment glycoprotein (G). A stabilized prefusion F (pre-F), multimeric G constructs, and chimeric proteins containing both pre-F and G were developed as protein subunit candidate vaccines. The proteins were evaluated for antigenicity and structural integrity using kinetic binding assays, electron microscopy, and other biophysical properties. Immunogenicity of the vaccine antigens was evaluated in mice. The stabilized pre-F trimer and hexameric G immunogens both induced serum neutralizing activity in mice, while the post-F trimer immunogen did not elicit neutralizing activity. The pre-F trimer covalently linked to three G monomers (pre-F/G) induced potent neutralizing antibody activity, elicited responses to the greatest diversity of antigenic sites, and is the lead candidate for clinical development. The specific stabilizing mutations and immunogen designs utilized for NiV were successfully applied to other henipaviruses, supporting the concept of identifying generalizable solutions for prototype pathogens as an approach to pandemic preparedness.

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.

Reliability of HEARTSMAP as a Tool for Evaluating Psychosocial Assessment Documentation Practices in Emergency Departments for Pediatric Mental Health Complaints.

OBJECTIVES: The goal of this study was to assess the reliability of HEARTSMAP as a standardized tool for evaluating the quality of psychosocial assessment documentation of pediatric mental health (MH) presentations to the emergency department (ED). In addition, we report on current documentation practices. METHODS: We conducted a retrospective cross-sectional study of pediatric (up to age 17) MH-related visits to four EDs between April 1, 2013, and March 31, 2014. The primary outcome was the inter-rater agreement when evaluating the completeness of pediatric emergency psychosocial assessments using the HEARTSMAP tool. The secondary outcome was to describe the adequacy of documentation of emergency pediatric MH assessments, using HEARTSMAP as a guide for a complete assessment. RESULTS: A total of 400 medical records (100 from each site) were reviewed. We observed near-perfect inter-rater agreement (κ = 0.99-1.00) regarding the presence of documentation and good-to-perfect agreement (κ = 0.71-1.00) regarding whether sufficient information was documented to score a severity level for every component of an emergency psychosocial assessment. Inter-rater agreement regarding whether referrals or resources were documented for identified needs was observed to be good to very good (κ = 0.62-0.98). Current psychosocial documentation practices were found to be inconsistent with significant variability in the presence of documentation pertaining to HEARTSMAP sections between medical centers and initial clinician assessor and whether specialized MH services were involved prior to discharge. CONCLUSIONS: The HEARTSMAP tool can be reliably used to assess pediatric psychosocial assessment documentation across a diverse range of EDs. Current documentation practices are variable and often inadequate, and the HEARTSMAP tool can aid in quality improvement initiatives to standardize and optimize care for the growing burden of pediatric mental illness.

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.

Proactive Tobacco Treatment for Smokers Using Veterans Administration Mental Health Clinics.

INTRODUCTION: Veterans with a mental health diagnosis have high rates of tobacco use but encounter low rates of treatment from providers. This study tested whether a proactive tobacco treatment approach increases treatment engagement and abstinence rates in Department of Veterans Affairs mental health patients. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: The study was performed from 2013 to 2017 and analyses were conducted in 2017. Investigators used the electronic medical record at four Veterans Administration facilities to identify patients documented as current smokers and who had a mental health clinic visit in the past 12 months. INTERVENTION: Patients were mailed an introductory letter and baseline survey. Survey respondents were enrolled and randomized to intervention (n=969) or control (n=969). Control participants received a list of usual Veterans Administration smoking services. Intervention participants received a motivational outreach call, multisession telephone counseling, and assistance with obtaining nicotine replacement therapy. MAIN OUTCOME MEASURES: Participants completed surveys at baseline, 6 months, and 12 months after randomization. The primary outcome was self-reported 7-day abstinence from cigarettes at 12-month follow-up. Secondary outcomes included use of cessation treatment, self-reported 7-day abstinence at 6-month follow-up, and 6-month prolonged abstinence at 12-month follow-up. RESULTS: At 12 months, intervention participants were more likely to report using telephone counseling (19% vs 3%, OR=7.34, 95% CI=4.59, 11.74), nicotine replacement therapy (47% vs 35%, OR=1.63, 95% CI=1.31, 2.03), or both counseling and nicotine replacement therapy (16% vs 2%, OR=11.93, 95% CI=6.34, 22.47). Intervention participants were more likely to report 7-day abstinence (19% vs 14%, OR=1.50, 95% CI=1.12, 2.01) and prolonged 6-month abstinence (16% vs 9%, OR=1.87, 95% CI=1.34, 2.61). After adjusting for non-ignorable missingness at follow-up, the intervention effects on 7-day and prolonged abstinence remained significant (p<0.05). CONCLUSIONS: Proactive outreach was more effective than usual Veterans Administration care at increasing treatment engagement and long-term abstinence in mental health patients. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01737281.

The influence of high-intensity interval training and moderate-intensity continuous training on sedentary time in overweight and obese adults.

High-intensity interval training (HIIT) elicits health benefits but it is unclear how HIIT impacts sedentary behaviour. In this preliminary study, we compared the effects of supervised HIIT or moderate-intensity continuous training (MICT) on sedentary time in overweight/obese adults. In both groups, percentage of time spent in sedentary activities was significantly reduced during the supervised exercise intervention (time main effect, P = 0.03), suggesting that both HIIT and MICT replaced time spent previously being sedentary.

Design, recruitment outcomes, and sample characteristics of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial.

This manuscript describes the study protocol, recruitment outcomes, and baseline participant characteristics for the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial. SPACE is a pragmatic randomized comparative effectiveness trial conducted in multiple VA primary care clinics within one VA health care system. The objective was to compare benefits and harms of opioid therapy versus non-opioid medication therapy over 12months among patients with moderate-to-severe chronic back pain or hip/knee osteoarthritis pain despite analgesic therapy; patients already receiving regular opioid therapy were excluded. Key design features include comparing two clinically-relevant medication interventions, pragmatic eligibility criteria, and flexible treat-to-target interventions. Screening, recruitment and study enrollment were conducted over 31months. A total of 4491 patients were contacted for eligibility screening; 53.1% were ineligible, 41.0% refused, and 5.9% enrolled. The most common reasons for ineligibility were not meeting pain location and severity criteria. The most common study-specific reasons for refusal were preference for no opioid use and preference for no pain medications. Of 265 enrolled patients, 25 withdrew before randomization. Of 240 randomized patients, 87.9% were male, 84.1% were white, and age range was 21-80years. Past-year mental health diagnoses were 28.3% depression, 17% anxiety, 9.4% PTSD, 7.9% alcohol use disorder, and 2.6% drug use disorder. In conclusion, although recruitment for this trial was challenging, characteristics of enrolled participants suggest we were successful in recruiting patients similar to those prescribed opioid therapy in usual care.

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.

Three Year Trends in Veterans Health Administration Utilization and Costs after Traumatic Brain Injury Screening among Veterans with Mild Traumatic Brain Injury.

Examination of trends in Veterans Health Administration (VHA) healthcare utilization and costs among veterans with mild traumatic brain injury (mTBI) is needed to inform policy, resource allocation, and treatment planning. The objective of this study was to assess the patterns of VHA healthcare utilization and costs in the 3 years following TBI screening among veterans with mTBI, compared with veterans without TBI. A retrospective cohort study of veterans who underwent TBI screening in fiscal year 2010 was conducted. We used VHA healthcare utilization and associated costs by categories of care to compare veterans diagnosed with mTBI (n = 7318) with those who screened negative (n = 75,294) and those who screened positive but had TBI ruled out (n = 3324). Utilization and costs were greatest in year 1, dropped in year 2, and then leveled off. mTBI diagnosis was associated with high rates of utilization. Each year, healthcare costs for those with mTBI were two to three times higher than for those who screened negative, and 20-25% higher than for those who screened positive but had TBI ruled out. A significant proportion of healthcare use and costs for veterans with mTBI were associated with mental health service utilization. The relatively high rate of VHA utilization and costs associated with mTBI over time demonstrates the importance of long-term planning to meet these veterans' needs. Identifying and engaging patients with mTBI in effective mental health treatments should be considered a critical component of treatment planning.

Thermosensitive Gel-Based Formulation for Intratumoral Delivery of Toll-Like Receptor 7/8 Dual Agonist, MEDI9197.

Toll-like receptor (TLR) agonists TLR 7/8, MEDI9197, is a imidazoquinoline analogue that can be used for cancer immunotherapy based on its efficacy toward a variety of tumors. Systemic administration of TLR agonists results in stimulation of the immune system throughout the entire body causing undesirable side effects. To minimize these adverse events, local administration of TLR agonists including intratumoral (IT) delivery has been introduced. Here, a poloxamer 407 thermogel formulation for IT delivery of a TLR 7/8 dual agonist, MEDI9197, is described in which the combination of the aqueous thermogel and the ethanolic TLR 7/8 dual agonist, MEDI9197, solution leads to precipitated drug particles within the gel. The in vitro release profile showed an initial burst followed by sustained release. A B16-OVA mouse tumor model was used to assess the in vivo pharmacokinetics, efficacy, and systemic cytokine and chemokine (cytokine) production of the poloxamer 407-based thermogel formulation. The pharmacokinetic evaluation showed that the agonist level within the tumor was reduced by ∼70% over 14 days while serum agonist levels indicated an initial burst at the 6-h time point followed by a drop in serum drug levels over the 14 days of the experiment. The tumor growth inhibition, survival, and serum cytokines for post-IT injection of the poloxamer 407 formulation showed that it slowly released TLR 7/8 agonist, MEDI9197, resulting in more efficacious tumor growth inhibition compared with control groups. In addition, the cytokine levels in circulation indicated that a dose increase led to a decrease in the serum inflammatory and interferon-inducible cytokines levels. This observation could be due to a reduction of drug diffusion and escape from the tumor site due to the precipitation of the drug inside the tumor leading to sustained release. IT delivery of TLR 7/8 dual agonist, MEDI9197, via a thermosensitive gel-based formulation was efficacious and could offer an alternate method of local drug delivery.

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

BACKGROUND: Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. OBJECTIVE: To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations. METHODS: Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low). 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.

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.

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.