Do veterans with risky substance use (RSU) use distinct pain treatment modalities?

BACKGROUND AND OBJECTIVES: Risky substance use (RSU) is common among people with chronic pain and is associated with worse pain treatment outcomes. Nonopioid treatment is recommended, but it is unknown whether people with RSU use different or fewer pain treatment modalities. This study describes use of different pain treatments by veterans with and without RSU and those receiving versus not receiving opioid medication. METHODS: Veterans (N = 924) who filed service-connected disability claims related to musculoskeletal conditions and rated their pain four or higher on the Numeric Rating Scale, reported on 25 different pain services in the preceding 90 days. Recent RSU was identified via Alcohol, Smoking, and Substance Involvement Test (ASSIST) cutoffs and/or nail sample toxicology. RESULTS: Overall, RSU was not associated with number of provider-delivered or self-delivered pain modalities. Over-the-counter medications (71%), self-structured exercise (69%), and nonopioid prescription medications (38%) were the most used modalities. Veterans receiving prescribed opioids (8.4%) were more likely to see primary care, receive injections, and attend exercise and/or meditation classes, compared to those without opioid prescriptions. DISCUSSION AND CONCLUSIONS: Opioid and nonopioid pain treatment utilization did not differ based on RSU, and those prescribed opioids were more likely to engage in other nonopioid pain treatments. Regardless of RSU, veterans appear willing to try provider-delivered (58%) and self-delivered (79%) pain treatment. SCIENTIFIC SIGNIFICANCE: In this first-ever evaluation of 25 different pain treatment modalities among veterans with and without RSU, people with RSU did not use less treatment modalities.

Adherence to Antiretrovirals and HIV Viral Suppression Under COVID-19 Pandemic Interruption - Findings from a Randomized Clinical Trial Using Ingestible Sensors to Monitor Adherence.

The COVID-19 pandemic had a significant impact on vulnerable populations, including people living with HIV. California implemented a coronavirus lockdown (stay-at-home order) in March 2020, which ended in January 2021. We evaluated the pandemic's impact on both clinical outcomes of HIV RNA viral load (VL) and retention rate in a randomized clinical trial conducted from May 2018 to October 2020. The intervention group took co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) pills from baseline through week 16. The IS system has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. Both the IS and usual care (UC) groups were followed monthly for 28 weeks. Longitudinal mixed-effects models with random intercept and slope (RIAS) were used to fit log VL and self-reported adherence. The sample size of the study was 112 (54 in IS). Overall, the retention rate at week 28 was 86%, with 90% before the lockdown and 83% after the lockdown. The lockdown strengthened the associations between adherence and VL. Before the lockdown, a 10% increase in adherence was associated with a 0.2 unit decrease in log VL (ß = -1.88, p = 0.004), while during the lockdown, the association was a 0.41-unit decrease (ß = -2.27, p = 0.03). The pandemic did not have a significant impact on our adherence-focused intervention. Our findings regarding the intervention effect remain valid. TRIAL REGISTRATION NUMBER: NCT02797262. Date registration: September 2015.

Integrating Financial Coaching and Referrals into a Smoking Cessation Program for Low-income Smokers: a Randomized Waitlist Control Trial.

BACKGROUND: Financial distress is a barrier to cessation among low-income smokers. OBJECTIVE: To evaluate an intervention that integrated financial coaching and benefits referrals into a smoking cessation program for low-income smokers. DESIGN: Randomized waitlist control trial conducted from 2017 to 2019. PARTICIPANTS: Adult New York City residents were eligible if they reported past 30-day cigarette smoking, had income below 200% of the federal poverty level, spoke English or Spanish, and managed their own funds. Pregnant or breastfeeding people were excluded. Participants were recruited from two medical centers and from the community. INTERVENTION: The intervention (n = 208) offered smoking cessation coaching, nicotine replacement therapy, money management coaching, and referral to financial benefits and empowerment services. The waitlist control (n=202) was usual care during a 6-month waiting period. MAIN MEASURES: Treatment engagement, self-reported 7-day abstinence, and financial stress at 6 months. KEY RESULTS: At 6 months, intervention participants reported higher abstinence (17% vs. 9%, P=0.03), lower stress about finances (ß, -0.8 [SE, 0.4], P=0.02), and reduced frequency of being unable to afford activities (ß, -0.8 [SE, 0.4], P=0.04). Outcomes were stronger among participants recruited from the medical centers (versus from the community). Among medical center participants, the intervention was associated with higher abstinence (20% vs. 8%, P=0.01), higher satisfaction with present financial situation (ß, 1.0 [SE, 0.4], P=0.01), reduced frequency of being unable to afford activities (ß, -1.0 [SE, 0.5], P=0.04), reduced frequency in getting by paycheck-to-paycheck (ß, -1.0 [SE, 0.4], P=0.03), and lower stress about finances in general (ß, -1.0 [SE, 0.4], P = 0.02). There were no group differences in outcomes among people recruited from the community (P>0.05). CONCLUSIONS: Among low-income smokers recruited from medical centers, the intervention produced higher abstinence rates and reductions in some markers of financial distress than usual care. The intervention was not efficacious with people recruited from the community. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03187730.

Counseling Veterans with Chronic Pain During the COVID-19 Pandemic: A Secondary Analysis of a Randomized Controlled Trial.

INTRODUCTION: Veterans with chronic pain could be vulnerable during the COVID-19 pandemic. We qualitatively explored the impact of the COVID-19 pandemic on a sample of veterans receiving brief counseling focused on pain management in an ongoing clinical trial and discuss how the pandemic affected the process of motivating veterans with chronic pain to engage in interdisciplinary multimodal pain treatment at the Department of Veteran Affairs. METHODS: Segments of audio-recorded counseling sessions containing content about the pandemic were transcribed and coded to identify key concepts emerging from individual counselor-participant transactions. Themes that emerged were examined with constant comparison analysis. RESULTS: Three major themes emerged. 1) The pandemic caused a disruption in pain management service delivery, resulting in changes to the way veterans receive services or manage their pain symptoms. 2) The pandemic offered opportunities for resilience and personal growth as veterans with chronic pain reflected on their lives and personal goals. 3) The pandemic brought veterans' mental health issues to the forefront, and these should be addressed as part of a comprehensive pain management approach. DISCUSSION: Discussion of the COVID-19 pandemic during pain treatment counseling sessions highlighted negative and positive ways participants were affected by the pandemic. These discussions provided counselors with a unique opportunity to facilitate behavior change by focusing on characteristics of resilience to motivate individuals with chronic pain to adapt and adopt positive behaviors and outlooks to improve their pain experience and quality of life. CONCLUSIONS: Counselors can leverage feelings of resilience and personal growth to motivate veterans' use of adaptive coping skills and a wider array of pain management services.

Increasing buprenorphine access for veterans with opioid use disorder in rural clinics using telemedicine.

Background:Having prescribers use clinical video teleconferencing (telemedicine) to prescribe buprenorphine to people with opioid use disorder (OUD) has shown promise but its implementation is challenging. We describe barriers, facilitators and lessons learned while implementing a system to remotely prescribe buprenorphine to Veterans in rural settings. Methods: We conducted a quality improvement project aimed at increasing the availability of medications for OUD (MOUD) to Veterans. This project focused on tele-prescribing buprenorphine to rural sites via a hub (centralized prescribers) and spoke (rural clinics) model. After soliciting a wide-range of inputs from site visits, qualitative interviews of key stakeholders at rural sites, and review of preliminary cases, a "how-to" toolkit was developed and iteratively refined to guide tele-prescribing of buprenorphine. After internal and external facilitation strategies were employed, Veterans with OUD at three clinics were transitioned to buprenorphine treatment via telemedicine. Results: Factors impacting adoption of the tele-prescribing intervention were mapped to the Consolidated Framework for Implementation Research (CFIR) constructs. Barriers to adoption included concerns about legality of tele-prescribing a controlled substance, conflicting interests between different stakeholders, and coordination with an existing buprenorphine program requiring more attendance and abstinence from Veterans than the tele-prescribing program required. Factors facilitating adoption included a sense of mission around combating the opioid epidemic, preexisting use of and comfort with tele-prescribing, and rural sites' control over Veterans referred to tele-prescribers. A total of 12 patients from rural areas were successfully transitioned onto buprenorphine, of whom 9 remained on buprenorphine 6 months after initiation of treatment. Conclusions: Implementing tele-prescribing was negotiated with stakeholders at the target clinics and operationalized in a toolkit to guide future efforts. Implementation issues can be addressed by activities that foster collaboration between hubs (centralized prescribers) and spokes (rural clinics) and by a toolkit that operationalizes tele-prescribing procedures.

The acceptability and feasibility of screening, brief intervention, and referral to treatment for pain management among new England veterans with chronic pain: A pilot study.

OBJECTIVES: Musculoskeletal disorders often lead to chronic pain in Veterans. Chronic pain puts sufferers at risk for substance misuse, and early intervention is needed for both conditions. This pilot study tested the feasibility and acceptability of a Screening, Brief Intervention, and Referral to Treatment for Pain Management intervention (SBIRT-PM) to help engage Veterans seeking disability compensation for painful musculoskeletal disorders in multimodal pain treatment and to reduce risky substance use, when indicated. METHODS: This pilot study enrolled 40 Veterans from 8 medical centers across New England in up to 4 sessions of telephone-based counseling using a motivational interviewing framework. Counseling provided education about, and facilitated engagement in, multimodal pain treatments. Study eligibility required Veterans be engaged in no more than 2 Veteran Affairs (VA) pain treatment modalities, and study participation involved a 12-week postassessment and semistructured interview about the counseling process. RESULTS: Majorities of enrolled Veterans screened positive for comorbid depression and problematic substance use. Regarding the offered counseling, 80% of participants engaged in at least one session, with a mean of 3 sessions completed. Ninety percent of participants completed the postassessment. Numerically, most measures improved slightly from baseline to week 12. In semistructured interviews, participants described satisfaction with learning about new pain care services, obtaining assistance connecting to services, and receiving support from their counselors. DISCUSSION: It was feasible to deliver SBIRT-PM to Veterans across New England to promote engagement in multimodal pain treatment and to track study outcomes over 12 weeks. Preliminary results suggest SBIRT-PM was well-received and has promise for the targeted outcomes.

The intertwined expansion of telehealth and buprenorphine access from a prescriber hub.

In this manuscript, we describe how efforts to increase access to buprenorphine for Opioid Use Disorder (OUD) through a telemedicine hub before and since the COVID-19 pandemic have played out in the Veterans Healthcare Administration (VHA) in New England. We look at how the COVID-19 pandemic and subsequent spike in opioid overdoses tilted the risk: benefit calculation for tele-prescribing a controlled substance such as buprenorphine toward expanding access to tele-buprenorphine. We conclude that there is a need for tele-buprenorphine hubs that can fill gaps in geographically dispersed healthcare systems.

Correspondence Between Retrospective and Momentary Self-Reported Posttraumatic Stress Disorder Symptoms: Evidence for Peak and End Effects in Veterans.

Validated retrospective self-report symptom rating scales are recommended for posttraumatic stress disorder (PTSD) screening and treatment. However, such reports may be affected by a respondent's most intense ("peak") or most recent ("end") symptoms. The present study evaluated the correspondence between PTSD symptoms assessed using a standard past-month retrospective rating scale and recorded by ecological momentary assessment (EMA) over the same period and tested hypotheses that retrospective scores would be predicted by peak and end-period momentary symptoms. Male U.S. veterans (N = 35) who served post-9/11 completed the PTSD Symptom Checklist for DSM-5 (PCL-5) at baseline and 1 month later. For 28 days during the intervening period, they received quasi-randomly timed text prompts to complete a modified version of the PCL-5 at that moment. Using multiple regression modeling, controlling for the number of completed EMAs and time (days) since the last EMA, we assessed the predictability of follow-up retrospective PCL-5 scores by (a) the mean of all momentary scores and (b) peak and last-day momentary scores. Retrospective PCL-5 scores were closest to peak scores, d = -0.31, and substantially higher than overall mean, d = 0.99, and last-day momentary scores, d = 0.94. In the regression model, peak symptom experiences and last-day momentary symptoms uniquely predicted follow-up PCL-5 scores over and above significant prediction by overall mean momentary symptom scores. In sum, participants' self-reported past-month PTSD symptom severity did not simply reflect an average over time. Additional questioning is needed to understand peak and recent symptom periods reflected in these estimates.

Energy, Exergy, Exergoeconomic and Exergoenvironmental Impact Analyses and Optimization of Various Geothermal Power Cycle Configurations.

Energy, exergy, and exergoeconomic evaluations of various geothermal configurations are reported. The main operational and economic parameters of the cycles are evaluated and compared. Multi-objective optimization of the cycles is conducted using the artificial bee colony algorithm. A sensitivity assessment is carried out on the effect of production well temperature variation on system performance from energy and economic perspectives. The results show that the flash-binary cycle has the highest thermal and exergy efficiencies, at 15.6% and 64.3%, respectively. The highest generated power cost and pay-back period are attributable to the simple organic Rankine cycle (ORC). Raising the well-temperature can increase the exergy destruction rate in all configurations. However, the electricity cost and pay-back period decrease. Based on the results, in all cases, the exergoenvironmental impact improvement factor decreases, and the temperature rises. The exergy destruction ratio and efficiency of all components for each configuration are calculated and compared. It is found that, at the optimum state, the exergy efficiencies of the simple organic Rankine cycle, single flash, double flash, and flash-binary cycles respectively are 14.7%, 14.4%, 12.6%, and 14.1% higher than their relevant base cases, while the pay-back periods are 10.6%, 1.5% 1.4%, and 0.6% lower than the base cases.

A hemi-spleen injection model of liver metastasis for prostate cancer.

BACKGROUND: Liver metastasis is not uncommon in men with metastatic castration-resistant prostate cancer (mCRPC), estimated at ~20% to 60% of advanced late-stage patients. Liver and other visceral metastases are associated with worse overall survival. Recent evidence suggests the frequency of visceral metastases may be increasing for reasons that are unclear but may be related to selective pressures induced by modern therapies, including second-generation antiandrogen receptor signaling inhibitors such as enzalutamide and abiraterone. Consequently, robust models to study the pathobiology of prostate cancer liver metastases and their response to therapy are urgently needed. METHODS: Hemi-spleen injection of human (LN95, PC3, VCaP, and MDA-PCa-2b) or syngeneic (Myc-CaP) prostate cancer cells (1 × 106 ) was performed to seed liver metastases via the splenic vessels. Plasma levels of prostate-specific antigen (PSA) were monitored longitudinally in human androgen receptor-positive (AR+) models. Immunohistochemical staining of AR and HoxB13 was performed to document the prostatic origin of hepatic lesions. RESULTS: LN95, PC3, and Myc-CaP produced distinct liver micrometastases that progressed to macrometastases by ~2 to 4 weeks postinoculation, while inoculation of MDA-PCa-2b and VCaP only produced occasional micrometastases and seeding of individual cells adjacent to blood vessels, respectively, at the time points analyzed. All lesions are characterized by positive staining for nuclear AR and/or the prostate-specific differentiation marker HoxB13 depending on the model. Circulating PSA levels are strongly correlated with overall tumor burden in mice seeded with LN95. Histologic micrometastases and low levels of circulating PSA are detected in mice seeded with MDA-PCa-2b at ~60 days postinoculation, but no circulating PSA was detected in animals inoculated with VCaP up to ~75 days despite the presence of rare AR+ cells in the liver. CONCLUSION: The studies reported herein establish intrasplenic injection as a robust model of mCRPC liver metastasis. In addition, circulating PSA was validated as a noninvasive biomarker to longitudinally monitor overall tumor burden when using PSA+ models. Therefore, this model can be used to interrogate the pathophysiology of prostate cancer liver metastases, the microenvironmental factors permissive to such growth, immunologic variables, and the response of hepatic lesions to therapy.

Pain Care in the Department of Veterans Affairs: Understanding How a Cultural Shift in Pain Care Impacts Provider Decisions and Collaboration.

OBJECTIVE: Over the past decade, the Department of Veterans Affairs (VA) has experienced a sizeable shift in its approach to pain. The VA's 2009 Pain Management Directive introduced the Stepped Care Model, which emphasizes an interdisciplinary approach to pain management involving pain referrals and management from primary to specialty care providers. Additionally, the Opioid Safety Initiative and 2017 VA/Department of Defense (DoD) clinical guidelines on opioid prescribing set a new standard for reducing opioid use in the VA. These shifts in pain care have led to new pain management strategies that rely on multidisciplinary teams and nonpharmacologic pain treatments. The goal of this study was to examine how the cultural transformation of pain care has impacted providers, the degree to which VA providers are aware of pain care services at their facilities, and their perceptions of multidisciplinary care and collaboration across VA disciplines. METHODS: We conducted semistructured phone interviews with 39 VA clinicians in primary care, mental health, pharmacy, and physical therapy/rehabilitation at eight Veterans Integrated Service Network medical centers in New England. RESULTS: We identified four major themes concerning interdisciplinary pain management approaches: 1) the culture of VA pain care has changed dramatically, with a greater focus on nonpharmacologic approaches to pain, though many "old school" providers continue to prefer medication options; 2) most facilities in this sample have no clear roadmap about which pain treatment pathway to follow, with many providers unaware of what treatment to recommend when; 3) despite multiple options for pain treatment, VA multidisciplinary teams generally work together to ensure that veterans receive coordinated pain care; and 4) veteran preferences for care may not align with existing pain care pathways. CONCLUSIONS: The VA has shifted its practices regarding pain management, with a greater emphasis on nonpharmacologic pain options. The proliferation of nonpharmacologic pain management strategies requires stakeholders to know how to choose among alternative treatments.

Screening, Brief Intervention, and Referral to Treatment for Pain Management for Veterans Seeking Service-Connection Payments for Musculoskeletal Disorders: SBIRT-PM Study Protocol.

BACKGROUND: Veterans with significant chronic pain from musculoskeletal disorders are at risk of substance misuse. Veterans whose condition is the result of military service may be eligible for a disability pension. Department of Veterans Affairs compensation examinations, which determine the degree of disability and whether it was connected to military service, represent an opportunity to engage Veterans in pain management and substance use treatments. A multisite randomized clinical trial is testing the effectiveness and cost-effectiveness of Screening, Brief Intervention, and Referral to Treatment for Pain Management (SBIRT-PM) for Veterans seeking compensation for musculoskeletal disorders. This telephone-based intervention is delivered through a hub-and-spoke configuration. DESIGN: This study is a two-arm, parallel-group, 36-week, multisite randomized controlled single-blind trial. It will randomize 1,100 Veterans experiencing pain and seeking service-connection for musculoskeletal disorders to either SBIRT-PM or usual care across eight New England VA medical centers. The study balances pragmatic with explanatory methodological features. Primary outcomes are pain severity and number of substances misused. Nonpharmacological pain management and substance use services utilization are tracked in the trial. SUMMARY: Early trial enrollment targets were met across sites. SBIRT-PM could help Veterans, at the time of their compensation claims, use multimodal pain treatments and reduce existing substance misuse. Strategies to address COVID-19 pandemic impacts on the SBIRT-PM protocol have been developed to maintain its pragmatic and exploratory integrity.

Internet-Based Pain Self-Management for Veterans: Feasibility and Preliminary Efficacy of the Pain EASE Program.

OBJECTIVE: To develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy-based, internet-delivered self-management program for chronic low back pain (cLBP) in veterans. METHODS: Phase I included program development, involving expert panel and participant feedback. Phase II was a single-arm feasibility and preliminary efficacy study of the Pain e-health for Activity, Skills, and Education (Pain EASE) program. Feasibility (ie, website use, treatment credibility, satisfaction) was measured using descriptive methods. Mixed models were used to assess mean within-subject changes from baseline to 10 weeks post-baseline in pain interference (primary outcome, West Haven-Yale Multidimensional Pain Inventory, scale of 0 to 6), pain intensity, mood, fatigue, sleep, and depression. RESULTS: Phase I participants (n = 15) suggested modifications including style changes, content reduction, additional "Test Your Knowledge" quizzes, and cognitive behavioral therapy skill practice monitoring form revisions for enhanced usability. In Phase II, participants (n = 58) were mostly male (93%) and White (60%), and had an average age of 55 years (standard deviation [SD] = 12) and moderate pain (mean score 5.9/10); 41 (71%) completed the post-baseline assessment. Participants (N = 58) logged on 6.1 (SD = 8.6) times over 10 weeks, and 85% reported being very or moderately satisfied with Pain EASE. Pain interference improved from a mean of 3.8 at baseline to 3.3 at 10 weeks (difference 0.5 [95% confidence interval 0.1 to 0.9], P = 0.008). Within-subject improvement also occurred for some secondary outcomes, including mood and depression symptoms. DISCUSSION: Veterans with cLBP may benefit from technology-delivered interventions, which may also reduce pain interference. Overall, veterans found that Pain EASE, an internet-based self-management program, is feasible and satisfactory for cLBP.

Brief Counseling for Veterans with Musculoskeletal Disorder, Risky Substance Use, and Service Connection Claims.

OBJECTIVE: High proportions of post-9/11 veterans have musculoskeletal disorders (MSDs), but engaging them in care early in their course of illness has been challenging. The service connection application is an ideal point of contact for referring veterans to early interventions for their conditions. DESIGN: Among MSD claimants who reported risky substance use, we pilot-tested a counseling intervention targeting pain and risky substance use called Screening Brief Intervention and Referral to Treatment-Pain Module (SBIRT-PM). Veterans were randomly assigned in a 2:1:1 ratio to SBIRT-PM, Pain Module counseling only, or treatment as usual (TAU). METHODS: Participants assigned to either counseling arm were offered a single meeting with a study therapist with two follow-up telephone calls as needed. Participants completed outcome assessments at four and 12 weeks after randomization. RESULTS: Of 257 veterans evaluated, 101 reported risky substance use and were randomized. Counseling was attended by 75% of veterans offered it and was well received. VA pain-related services were used by 51% of participants in either of the pain-focused conditions but only by 27% in TAU (P < 0.04). Starting with average pain severity ratings of 5.1/10 at baseline, only minimal changes in mean pain severity were noted regardless of condition. Self-reported risky substance use was significantly lower over time in the SBIRT-PM condition relative to the two other conditions (P < 0.02). At week 12, proportions of veterans reporting risky substance use were 0.39, 0.69, and 0.71 for the SBIRT-PM, Pain Module counseling, and TAU conditions, respectively. CONCLUSIONS: SBIRT-PM shows promise as a way to engage veterans in pain treatment and reduce substance use.

Impulsivity interacts with momentary PTSD symptom worsening to predict alcohol use in male veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) is prevalent among veterans who served post-9/11, and co-occurs with problem alcohol and substance use. Studies using ecological momentary assessment have examined the temporal association between time-varying PTSD symptoms and alcohol use. Results suggest individual differences in these associations. OBJECTIVES: We tested hypotheses that alcohol use measured by momentary assessment would be explained by acute increases in PTSD symptoms, and the PTSD-alcohol association would be moderated by trait impulsivity. METHODS: A sample of 28 male post-9/11-era veterans who reported past-month PTSD symptoms and risky alcohol use were enrolled. On a quasi-random schedule, participants completed three electronic assessments daily for 28 days measuring past 2-h PTSD symptoms, alcohol, and substance use. At baseline, trait impulsivity was measured by the Barratt Impulsiveness Scale. Past-month PTSD symptoms and alcohol use were measured. Using three-level hierarchical models, number of drinks recorded by momentary assessment was modeled as a function of change in PTSD symptoms since last assessment, controlling for lag-1 alcohol and substance use and other covariates. A cross-level interaction tested moderation of the within-time PTSD-alcohol association by impulsivity. RESULTS: A total of 1,522 assessments were completed. A positive within-time association between PTSD symptom change and number of drinks was demonstrated. The association was significantly moderated by impulsivity. CONCLUSION: Results provide preliminary support for a unique temporal relationship between acute PTSD symptom change and alcohol use among veterans with trait impulsiveness. If replicated in a clinical sample, results may have implications for a targeted momentary intervention.

Financial Capability: Clinicians' Assessment of Beneficiaries With Dual Diagnoses.

OBJECTIVE: Adults with mental health disorders whose ability to work is sufficiently impeded are entitled to financial supports from the Social Security Administration. Beneficiaries determined to be incapable of managing these funds are supposed to be assigned a representative payee to assist beneficiaries in meeting their needs. However, patterns of payee assignment suggest that payee assignment is impacted by factors other than those the Social Security Administration instructs clinicians to consider. In this study, we tested the association between clinicians' judgments of their clients' financial capability and hypothesized predictors (demographic characteristics, psychiatric diagnosis, recent alcohol and other substance use, self-rated money mismanagement, recent homelessness, and provider characteristics). We posited that predictors might act indirectly on capability judgment via their impact on beneficiaries' money management. METHODS: Altogether, 261 people receiving intensive mental health care who did not have payees or fiduciaries were enrolled after providing written informed consent. These beneficiaries completed in-person assessment interviews, reporting demographic characteristics, treatment history, substance use, and homelessness. Mental health clinicians identified by the beneficiaries were enrolled in the study and asked to judge their clients' financial capability with standard Social Security instructions for determining capability. Bivariate associations between hypothesized predictors and clinicians' determinations of incapability were tested. In multivariate probit regression models, incapability determination was modeled as a function of all beneficiary and clinician characteristics that had significant bivariate associations with the outcome. RESULTS: Providers identified 24% of their clients as financially incapable. Determinations of financial incapability were unrelated to any beneficiary or provider demographic characteristics but were positively associated with money mismanagement, homelessness, and having a psychotic disorder. Alcohol use and other substance use were only significantly associated with capability determinations indirectly through their effects on money mismanagement. CONCLUSIONS: Providers' judgments of beneficiaries' capability to manage their funds were associated with factors that were consistent with Social Security Administration guidelines and were, importantly, not associated with personal characteristics. This finding suggests that guidelines can be fairly applied by clinicians and that reported inconsistencies in payee assignment are accounted for by other factors. The Social Security Administration is currently considering other approaches to standardize capability determinations.

Anticancer activities of emetine prodrugs that are proteolytically activated by the prostate specific antigen (PSA) and evaluation of in vivo toxicity of emetine derivatives.

Emetine is a small molecule protein synthesis inhibitor that is toxic to all cell types and therefore suitable for complete killing of all types of heterogeneous cancer cells within a tumor. It becomes significantly inactive (non-toxic) when derivatized at its N-2' secondary amine. This provides a strategy for targeting emetine to cancerous tumor without killing normal cells. In this report, PSA activatable peptide prodrugs of emetine were synthesized. To overcome steric hindrances and enhance protease specific cleavage, a 2-stage prodrug activation process was needed to release emetine in cancer cells. In this 2-stage process, emetine prodrug intermediates are coupled to PSA peptide substrate (Ac-His-Ser-Ser-Lys-Leu-Gln) to obtain the full prodrug. Both prodrug intermediates 10 (Ala-Pro-PABC-Emetine) and 14 (Ser-Leu-PABC-Emetine) were evaluated for kinetics of hydrolysis to emetine and potency [Where PABC = p-aminobenzyloxycarbonyl]. While both intermediates quantitatively liberate emetine when incubated under appropriate conditions, upon coupling of PSA substrate to give the full prodrugs, only prodrug 16, the prodrug obtained from 14 was hydrolyzable by PSA. Cytotoxicity studies in PSA producing LNCaP and CWR22Rv1 confirm the activation of the prodrug by PSA with an IC50 of 75 nM and 59 nM respectively. The cytotoxicity of 16 is significantly reduced in cell lines that do not produce PSA. Further, in vivo toxicity studies are done on these prodrugs and other derivatives of emetine. The results show the significance of conformational modulation in obtaining safe emetine prodrugs.

A case of concurrent silent sinus syndrome, thyroid eye disease, idiopathic orbital inflammatory syndrome, and dacryoadenitis.

This is a retrospective case description of a single female patient found to have concomitant bilateral silent sinus syndrome, bilateral thyroid eye disease, unilateral dacryoadenitis, and idiopathic orbital inflammation that presented as progressive unilateral right-sided proptosis. The spectrum of inflammatory orbital diseases can make discerning between different entities challenging, but more unique in this case was the simultaneous presentation with bilateral silent sinus syndrome, a rare entity in its own right. Identifying each of these concurrent disease processes is important to establishing a multidisciplinary treatment approach to address all the patient's orbital and peri-orbital pathology. We hope to highlight the clinical and radiographic findings unique to each of these entities and share our approach to treatment in this complex case.

The learning curve in endoscopic endonasal resection of craniopharyngiomas.

OBJECTIVE There is a paucity of literature regarding the learning curve associated with performing endoscopic endonasal cranial base surgery. The purpose of this study was to determine to what extent a learning curve might exist for endoscopic endonasal resection in cases of craniopharyngiomas. METHODS A retrospective review was performed for all endoscopic endonasal craniopharyngioma resections performed at Thomas Jefferson University from 2005 to 2015. To assess for a learning curve effect, patients were divided into an early cohort (2005-2009, n = 20) and a late cohort (2010-2015, n = 23). Preoperative demographics, clinical presentation, imaging characteristics, extent of resection, complications, tumor control, and visual and endocrine outcomes were obtained. Categorical variables and continuous variables were compared using a 2-sided Fisher's exact test and t-test, respectively. RESULTS Only the index operation performed at the authors' institution was included. There were no statistically significant differences between early and late cohorts in terms of patient age, sex, presenting symptoms, history of surgical or radiation treatment, tumor size or consistency, hypothalamic involvement, or histological subtype. The rate of gross-total resection (GTR) increased over time from 20% to 65% (p = 0.005), and the rate of subtotal resection decreased over time from 40% to 13% (p = 0.078). Major neurological complications, including new hydrocephalus, meningitis, carotid artery injury, or stroke, occurred in 6 patients (15%) (8 complications) in the early cohort compared with only 1 (4%) in the late cohort (p = 0.037). CSF leak decreased from 40% to 4% (p = 0.007). Discharge to home increased from 64% to 95% (p = 0.024). Visual improvement was high in both cohorts (88% [early cohort] and 81% [late cohort]). Rate of postoperative panhypopituitarism and permanent diabetes insipidus both increased from 50% to 91% (p = 0.005) and 32% to 78% (p = 0.004), which correlated with a significant increase in intentional stalk sacrifice in the late cohort (from 0% to 70%, p < 0.001). CONCLUSIONS High rates of near- or total resection and visual improvement can be achieved using an endoscopic endonasal approach for craniopharyngiomas. However, the authors did find evidence for a learning curve. After 20 cases, they found a significant decrease in major neurological complications and significant increases in the rates of GTR rate and discharge to home. Although there was a large decrease in the rate of postoperative CSF leak over time, this was largely attributable to the inclusion of very early cases prior to the routine use of vascularized nasoseptal flaps. There was a significant increase in new panhypopituitarism and diabetes insipidus, which is attributable to increase rates of intentional stalk sacrifice.

Sinonasal malignancy: What to do with an unexpected pathology result?

BACKGROUND: Endoscopic sinus surgery has become the mainstay in surgical treatment of sinusitis and nasal polyps. While rare, diagnostic discrepancies or pathological contamination during routine specimen analysis has been described. Thus, an accurate diagnosis and indication for surgery are mandatory before proceeding with surgical intervention. METHODS: We present the case of a 40-year-old female patient who underwent endoscopic sinus surgery (ESS) for chronic sinusitis without nasal polyposis and fragments of squamous cell carcinoma (SCC) were found in the pathology specimen. RESULTS: We propose an algorithm to help guide physicians presented with a tissue diagnosis that does not match the clinical scenario. Moreover, we discuss strategies to help prevent medical errors and the importance of DNA genetic analysis in this situation. CONCLUSION: When an unexpected diagnosis occurs, the pathology slides should be reviewed for a second opinion. If the unexpected diagnosis is confirmed, the tissue should undergo STR genetic analysis to ensure against tissue contamination.