Veterans Affairs Puget Sound Health Research Articles

S261 Effect of a Patient Navigator on Colonoscopy Completion in FIT Positive Patients Refractory to Initial Scheduling Attempts

Introduction: Decreased time from positive fecal immunochemical test (FIT) to colonoscopy is associated with decreased morbidity and mortality from colorectal cancer. However, colonoscopy is often delayed or forgone for a variety of reasons. Prior studies have shown that patient navigation for FIT+ patients increases the likelihood of colonoscopy completion. The purpose of this study was to evaluate the impact of a patient navigator on improvement in colonoscopy completion in Veterans who had not completed timely colonoscopy after FIT+. Methods: Patients in the Veterans Affairs Puget Sound Health Care System with FIT+ between 1/1/2020 and 6/30/2021 who had not yet completed colonoscopy were randomized in 11/2021 to: 1) navigation with a mailed letter and phone call from a trained, non-clinical staff member, 2) mailed letter only, or 3) control. The patient navigator provided basic education to the patient, elicited barriers to care, and facilitated seamless interaction with the primary care team. Demographic variables were recorded from the medical record. The Care Assessment Need (CAN) score was used to assess comorbid status. Outcomes were assessed as of 6/1/2022. Binary logistic regression and Kaplan Meier analyses were performed using SPSS. Results: 170 FIT+ patients were identified and 56, 56, and 58 patients were assigned to the Navigator, Mailed Letter, and Control groups, respectively. Patient demographics were similar between cohorts (Table). Colonoscopy completion was significantly increased in the Navigator group (p < 0.05), while the letter alone had no significant impact (Table). Navigation was also associated with improved documentation of reasons for no colonoscopy (p < 0.05). Adjusting for measured covariates, compared to the Navigator group, the odds of colonoscopy completion was significantly lower for the Mailed Letter group (OR 0.31 (CI 0.14-0.67)) and the Control group (OR 0.37 (CI 0.17-0.78)). Kaplan Meier analysis (Figure) revealed statistically significant differences in time to colonoscopy between the three groups. Conclusion: Patient navigation with a trained non-clinical staff member significantly improves colonoscopy completion following FIT+ in patients who are refractory to initial attempts at timely colonoscopy. Mailing a letter alone had no significant benefit. Further efforts are needed to ensure timely and complete diagnostic evaluation of patients with FIT+ screening. This study was sponsored by a grant from the American Cancer Society.Figure 1.: Kaplan Meier for Colonoscopy Completion Following FIT+ (p = 0.05) Table 1. - Demographic Information and Descriptive Results Overall (n = 170) Navigator (n = 56) Mailed Letter Only (n = 56) Control (n = 58) Mean Age (years) 67.3 65.8 68.6 67.5 Sex (% men) 90.1 89.3 91.1 91.4 Race (% white) 80.1 76.8 85.7 79.3 Hispanic Status (% Hispanic) 0.01 0.0 0.02 0.0 Mean CAN Score 60.0 62.2 57.7 60.0 Referral to GI Placed (%) 82.9 87.5 85.7 75.9 Colonoscopy Completed (%) 28.8 41.1 23.2 22.4 Colonoscopy Completed or Appropriate Reason for no Colonoscopy (%) 47.1 66.1 33.9 39.7 Median Days from FIT+ to Colonoscopy 211 230 235 196

Postanesthesia Recovery Unit Optimization for Patients With Postictal Agitation Secondary to Electroconvulsive Therapy.

The occurrence of postictal agitation (PIA) can rapidly alter and intensify the level of care that electroconvulsive therapy (ECT) patients require during their recovery in the postanesthesia care unit (PACU). This operational analysis was undertaken to determine the impact PIA has on phase 1 PACU resources. This operational analysis was undertaken at the Seattle Division of the US Department of Veterans Affairs Puget Sound Health Care System. From August 2019 to April 2020, we prospectively collected data on the recovery from ECT of 61 unique patients who underwent a total of 334 ECT sessions. Utilization of PACU resources was assessed by determining the PACU length of stay (LOS), onset of PIA, severity of PIA, and duration of agitation in encounters complicated by PIA. Seventy-nine occurrences of PIA occurred during the 334 ECT encounters. The mean ± SD PACU LOS was longer in encounters complicated by the occurrence of PIA compared with those not complicated by PIA (72 ± 32 and 59 ± 18 minutes respectively; P -value <0.05). Postanesthesia care unit LOS and mean duration of agitation increased as severity of PIA increased. The occurrence of PIA can rapidly alter and intensify the level of care that ECT patients may require. Postictal agitation has a significant impact on the phase 1 PACU LOS of patients undergoing ECT. Phase 1 PACU staffing models should factor in the acute and prolonged care needs of patients who develop PIA during the recovery from ECT.

Removal of Small, Asymptomatic Kidney Stones and Incidence of Relapse

BackgroundThe benefits of removing small (≤6 mm), asymptomatic kidney stones endoscopically is unknown. Current guidelines leave such decisions to the urologist and the patient. A prospective study involving older, nonendoscopic technology and some retrospective studies favor observation. However, published data indicate that about half of small renal stones left in place at the time that larger stones were removed caused other symptomatic events within 5 years after surgery.MethodsWe conducted a multicenter, randomized, controlled trial in which, during the endoscopic removal of ureteral or contralateral kidney stones, remaining small, asymptomatic stones were removed in 38 patients (treatment group) and were not removed in 35 patients (control group). The primary outcome was relapse as measured by future emergency department visits, surgeries, or growth of secondary stones.ResultsAfter a mean follow-up of 4.2 years, the treatment group had a longer time to relapse than the control group (P<0.001 by log-rank test). The restricted mean (±SE) time to relapse was 75% longer in the treatment group than in the control group (1631.6±72.8 days vs. 934.2±121.8 days). The risk of relapse was 82% lower in the treatment group than the control group (hazard ratio, 0.18; 95% confidence interval, 0.07 to 0.44), with 16% of patients in the treatment group having a relapse as compared with 63% of those in the control group. Treatment added a median of 25.6 minutes (interquartile range, 18.5 to 35.2) to the surgery time. Five patients in the treatment group and four in the control group had emergency department visits within 2 weeks after surgery. Eight patients in the treatment group and 10 in the control group reported passing kidney stones.ConclusionsThe removal of small, asymptomatic kidney stones during surgery to remove ureteral or contralateral kidney stones resulted in a lower incidence of relapse than nonremoval and in a similar number of emergency department visits related to the surgery. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Veterans Affairs Puget Sound Health Care System; ClinicalTrials.gov number, NCT02210650.)

Editorial Commentary.

No AccessUrology PracticeHealth Policy1 Sep 2022Editorial CommentaryThis article comments on the following:Radium-223 Utilization Patterns and Outcomes in Clinical Practiceis a letter which has replyReply by Authors Yaw A. Nyame Yaw A. NyameYaw A. Nyame Department of Urology, University of Washington, Seattle, Washington Division of Urology, Veterans Affairs Puget Sound Health Care, Seattle, Washington More articles by this author View All Author Informationhttps://doi.org/10.1097/UPJ.0000000000000316.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Commentary." Urology Practice, 9(5), p. 413

Multicenter, Head-to-Head, Real-World Validation Study of Seven Automated Artificial Intelligence Diabetic Retinopathy Screening Systems.

OBJECTIVEWith rising global prevalence of diabetic retinopathy (DR), automated DR screening is needed for primary care settings. Two automated artificial intelligence (AI)–based DR screening algorithms have U.S. Food and Drug Administration (FDA) approval. Several others are under consideration while in clinical use in other countries, but their real-world performance has not been evaluated systematically. We compared the performance of seven automated AI-based DR screening algorithms (including one FDA-approved algorithm) against human graders when analyzing real-world retinal imaging data.RESEARCH DESIGN AND METHODSThis was a multicenter, noninterventional device validation study evaluating a total of 311,604 retinal images from 23,724 veterans who presented for teleretinal DR screening at the Veterans Affairs (VA) Puget Sound Health Care System (HCS) or Atlanta VA HCS from 2006 to 2018. Five companies provided seven algorithms, including one with FDA approval, that independently analyzed all scans, regardless of image quality. The sensitivity/specificity of each algorithm when classifying images as referable DR or not were compared with original VA teleretinal grades and a regraded arbitrated data set. Value per encounter was estimated.RESULTSAlthough high negative predictive values (82.72–93.69%) were observed, sensitivities varied widely (50.98–85.90%). Most algorithms performed no better than humans against the arbitrated data set, but two achieved higher sensitivities, and one yielded comparable sensitivity (80.47%, P = 0.441) and specificity (81.28%, P = 0.195). Notably, one had lower sensitivity (74.42%) for proliferative DR (P = 9.77 × 10−4) than the VA teleretinal graders. Value per encounter varied at $15.14–$18.06 for ophthalmologists and $7.74–$9.24 for optometrists.CONCLUSIONSThe DR screening algorithms showed significant performance differences. These results argue for rigorous testing of all such algorithms on real-world data before clinical implementation.

Multi-Institutional Collaborative Resident Education in the Era of COVID-19.

The 2019-2020 coronavirus pandemic has had a significant impact on all aspects of health care. Decrease in clinical and operative volume and limitations for conferences has drastically decreased educational opportunities for resident trainees. We describe the formation and initial success of the Collaborative Online Video Didactics lecture series, a multi-institutional online video didactics collaboration. Zoom data extraction and postlecture evaluation surveys were used to collect data on the impact of the pandemic on local educational activities as well as feedback about the lecture series. Lectures are being given by faculty from 35 institutions. The twice daily, hour-long webinar averages more than 470 live viewers per session with an average of 33.5 questions per session and has over 7,000 YouTube views of the recordings after the first 2 weeks. Viewers reported significant decreases in outpatient (75.2%), inpatient (64.9%) and operating room (77.7%) volumes at local programs, and only half (52.7%) of the survey responders indicated an increase in didactics locally. The lectures have been well-received, with over 90% of respondents giving the lecturers and series above average or excellent ratings. A significant majority of responders indicated that the lecture series has allowed for ongoing education opportunities during the pandemic (95.0%), helped to access faculty experts from other institutions (92.3%) and provided a sense of community connectedness during this period of social isolation (81.7%). We strongly encourage other institutions and trainees to participate in the didactic series and hope that this series can continue to evolve and be of benefit beyond the pandemic.

Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience.

BackgroundAutologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging.MethodsWe examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37).ResultsTen patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib.ConclusionOur findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Adherence of oral targeted agents in patients with B-cell malignancies.

e18301 Background: Oral targeted agents (OTAs) are rapidly changing the management of B-cell malignancies (BCM) and introducing challenges in prescribing practices and communication between patients, their clinicians, and pharmacists. Emerging data suggests dose interruptions impair OTA efficacy in BCM. However, infrastructure to ensure best practices may be outstripped by increasing OTA use in some clinics. We evaluated adherence to OTAs for BCMs at the Veterans Affairs Puget Sound Health Care System to identify opportunities for quality improvement in prescribing practices and patient education. Methods: Consecutive patients treated with OTAs for BCMs from 2014 to 2018 were examined by detailed chart review and included if they used an OTA uninterrupted for ≥ 30 days. OTA adherence was assessed by 1) identification of medication gaps ≥ 8 days not attributable to medication toxicity or disease progression and 2) ReComp, a validated electronic pharmacy refill adherence algorithm in which a value of 1 corresponds with perfect adherence and deviations from 1 correlate linearly with either over- or under- supply. Logistic regression modeling assessed for independent predictors of adherence. Results: Fifty patients were evaluated and 39 met inclusion criteria. They were prescribed 42 unique OTAs, including ibrutinib, venetoclax, idelalsib, and acalabrutinib over a total of 33,655 days, with a median duration of 420 days (range 60 to 1687). Twenty-three patients (59%) had at least one medication adherence gap ≥ 8 days. Five patients (13%) had ≥ 3 eight-day gaps. The study population had a mean ReComp value of 1.02 (median 0.99, standard deviation 0.15). Medication over-supply was identified in 46% and a quarter of patients were adherent &lt; 93% of the time. No statistically significant correlations were identified between either measure of adherence and examined factors related to socio-demographics and comorbidities. Conclusions: In our institution, a significant percentage of patients prescribed OTAs for BCMs experienced suboptimal adherence. These data identify opportunities to improve disease-related outcomes and costs. Initiatives to improve education and automated monitoring of OTA refills are under evaluation.

Mental and Physical Health Correlates of Pain Treatment Utilization Among Veterans With Chronic Pain: A Cross-sectional Study.

The annual cost of treatment and lost productivity due to chronic pain is estimated to be $635 billion within the USA. Self-management treatments for chronic pain result in lower health care costs and lower utilization of provider-management treatments, such as hospitalization and medication use. The current study sought to identify and characterize patient factors and health conditions associated with chronic pain treatment utilization to inform ways to improve engagement in self-management pain treatment (e.g., applying heat or ice, exercising, or practicing relaxation). This study predicted (1) greater pain intensity and pain interference would be associated with greater utilization of self-management treatments and (2) this association would be moderated by patient factors (gender and age) and health comorbidities (anxiety, trauma, depression, and sleep disturbance). Baseline data from a three-arm clinical trial were collected for 127 Veterans seeking treatment for chronic pain. Veterans were recruited via clinician referral and medical record review at the Veterans Affairs Puget Sound Health Care System, Washington, USA. Self-management treatments were more utilized than provider-management treatments. Pain intensity and pain interference were not uniquely associated with provider-management or self-management treatment utilization after controlling for demographics and mental health status. Sleep disturbance moderated the relationship between pain interference and provider-management treatment utilization. Depression moderated the relationship between pain intensity and provider-management treatment utilization. While study conclusions may not generalize to all Veteran populations, findings suggest that Veterans with chronic pain were more likely to seek provider-management treatments when experiencing high-pain interference and high-sleep disturbance. In addition, Veterans were more likely to seek provider-management treatments when experiencing low-pain intensity and high-depression symptoms.

Abstracts from The 35th Annual National Neurotrauma Symposium July 7-12, 2017 Snowbird, Utah.

Abstracts from The 35th Annual National Neurotrauma Symposium July 7-12, 2017 Snowbird, Utah.

Improving Family Meetings in Intensive Care Units: A Quality Improvement Curriculum.

Family meetings in the intensive care unit are associated with beneficial outcomes for patients, their families, and health care systems, yet these meetings often do not occur in a timely, effective, reliable way. The Department of Veterans Affairs Comprehensive End-of-Life Care Implementation Center sponsored a national initiative to improve family meetings in Veterans Affairs intensive care units across the United States. Process measures of success for the initiative were identified, including development of a curriculum to support facility-based quality improvement projects to implement high-quality family meetings. Identified curriculum requirements included suitability for distance learning and applicability to many clinical intensive care units. Curriculum modules were cross-mapped to the "Plan-Do-Study-Act" model to aid in planning quality improvement projects. A questionnaire was e-mailed to users to evaluate the curriculum's effectiveness. Users rated the curriculum's effectiveness in supporting and achieving aims of the initiative as 3.6 on a scale of 0 (not effective) to 4 (very effective). Users adapted the curriculum to meet local needs. The number of users increased from 6 to 17 quality improvement teams in 2 years. All but 3 teams progressed to implementation of an action plan. Users were satisfied with the effectiveness and adaptability of a family-meeting quality improvement curriculum to support implementation of a quality improvement project in Veterans Affairs intensive care units. This tool may be useful in facilitating projects to improve the quality of family meetings in other intensive care units.

"Maybe They Don't Even Know That I Exist": Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease.

Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease. As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes. The following three themes emerged from interviews with patients' family members and friends: (1) their roles in care and planning were fluid over the course of the patient's illness, shaped by the patients' changing needs and their readiness to involve those close to them; (2) their involvement in patients' care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and (3) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient. Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients' care, and highlight the potential value of offering opportunities for engagement throughout the course of illness.

Veteran Preferences Regarding Wireless Management of Positive Airway Pressure for Obstructive Sleep Apnea at a Tertiary Health-Care System.

Timely monitoring of obstructive sleep apnea (OSA) therapy can be a challenge amid conflicting pressures of rising patient volume and shortage of sleep medicine providers. Positive airway pressure (PAP) devices with wireless modem technology have the potential to improve patient access to care and streamline work load, yet little is known about patient attitudes toward telehealth integration among veterans with sleep apnea. As part of a larger quality improvement initiative at the Veterans Affairs (VA) Puget Sound Health Care System, we elicited veterans' preferences toward modem versus traditional PAP data download, including patient attitudes and factors affecting those preferences. We conducted an anonymous survey of veterans without previous CPAP experience presenting for initial device setup and training at VA Puget Sound PAP clinics. Surveys assessed subject demographics, PAP download preferences (modem vs mail), and Likert-type scale ratings of importance placed on factors including convenience and information privacy. Using multinomial logistic regression, we examined the association between convenience rating and download preference, adjusting for information privacy rating, age, and commute time. Of 444 surveys analyzed, respondents were primarily male with a mean age of 52 y. Most respondents reported taking ≥ 30 min to commute to the PAP clinic. Convenience was rated as the most important factor affecting download preferences. Veteran preferences regarding PAP download method were mixed, with 47% preferring modem, 38% preferring memory card mail-in, and 15% undecided. A higher rating of convenience was significantly associated with modem preference, both before and after adjustment for information privacy rating, commute time, and veteran age (adjusted relative risk ratio 1.67, P < .001, 95% CI 1.40-1.99). PAP data download preferences were mixed among new veteran users. Veterans placed a high value on the potentially competing concerns of convenience and information privacy. Veterans preferring modem factored convenience as important in their decision making, independent of privacy concerns.

Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?

There is growing interest in efforts to enhance advance care planning for patients with kidney disease. Our goal was to elicit the perspectives on advance care planning of multidisciplinary providers who care for patients with advanced kidney disease. Between April and December of 2014, we conducted semistructured interviews at the Department of Veterans Affairs Puget Sound Health Care System with 26 providers from a range of disciplines and specialties who care for patients with advanced kidney disease. Participants were asked about their perspectives and experiences related to advance care planning in this population. Interviews were audiotaped, transcribed, and analyzed inductively using grounded theory. The comments of providers interviewed for this study spoke to significant system-level barriers to supporting the process of advance care planning for patients with advanced kidney disease. We identified four overlapping themes: (1) medical care for this population is complex and fragmented across settings and providers and over time; (2) lack of a shared understanding and vision of advance care planning and its relationship with other aspects of care, such as dialysis decision making; (3) unclear locus of responsibility and authority for advance care planning; and (4) lack of active collaboration and communication around advance care planning among different providers caring for the same patients. The comments of providers who care for patients with advanced kidney disease spotlight both the need for and the challenges to interdisciplinary collaboration around advance care planning for this population. Systematic efforts at a variety of organizational levels will likely be needed to support teamwork around advance care planning among the different providers who care for patients with advanced kidney disease.

Integrating Chronic Care for AUDs Into Primary Care Settings

Integrating Chronic Care for AUDs Into Primary Care Settings

In Vitro Activity of Retapamulin and Antimicrobial Susceptibility Patterns in a Longitudinal Collection of Methicillin-Resistant Staphylococcus aureus Isolates from a Veterans Affairs Medical Center.

Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial agents, including mupirocin, for 403 MRSA isolates collected longitudinally from a naive population at the Veterans Affairs Puget Sound Health Care System. The MICs for retapamulin had a unimodal distribution, ranging from 0.008 to 0.5 μg/ml. One isolate had an MIC of >16 μg/ml, was also resistant to clindamycin and erythromycin, and was recovered from the nares of a patient undergoing hemodialysis. Twenty-four isolates (6%) and 11 isolates (3%) demonstrated low-level resistance (MICs of 8 to 64 μg/ml) and high-level resistance (MICs of ≥ 512 μg/ml), respectively, to mupirocin. Isolates were recovered from 10 patients both before and after mupirocin therapy. Of those, isolates from 2 patients demonstrated MIC changes postmupirocin therapy; in both cases, however, strain typing demonstrated that the pre- and postmupirocin strains were different. A total of 386 isolates (96%) had vancomycin MICs of ≤ 1.0 μg/ml; 340 isolates (84%) were resistant to levofloxacin, 18 isolates (4.5%) were resistant to trimethoprim-sulfamethoxazole, and 135 isolates (33%) had elevated MICs of 4 μg/ml for linezolid. The baseline levels of resistance were low for mupirocin (9%) and even lower for retapamulin (0.25%) Although the use of mupirocin is currently the standard therapy for decolonization practices, the activity of retapamulin warrants its consideration as an alternative therapy in MRSA decolonization regimens.

Intrinsic clustering of treatment outcome in recovery from opioid use disorder: Results from starting treatment with agonist replacement therapies

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e137 systems. This qualitative study aimed to investigate experiences with a peer delivered strengths-based case management (CM) program to link addiction patients to HIV services in St. Petersburg, Russia. Methods:We recruited 38HIV-infected addiction patients from LINC (Linking Infectious and Narcology Care), a randomized trial (n=350) testing a CM program. Using a semi-structured questionnaire, we conducted 6 focus groups (5 to 8 patients post-CM) in the Russian language. Discussions were audiorecorded, translated and transcribed into English. Two investigators coded transcriptions and analyzed data thematically using Nvivo. Results: Participants were 84% male, median age 36 years, 37% employed, median 14 years of drug use and 7 years since HIV diagnosis. Post-intervention linkage to HIV care was reported by 68%. Those who linked to HIV services embraced the concept of CM, preferably from a peer in recovery, as facilitating their navigation of HIV services in Russia’s fragmented health system. Some felt CM empowered their copingwithhealth systemchallenges and stigma. Among participants not connecting to HIV services, themes such as “lack of motivation”, “no need for HIV care” and “active drug use” emerged as major barriers both to engage with CM and to seek HIV care. Conclusions: Russian addiction patients who linked to HIV care credit CM for facilitating linkage,while those not linking attribute it to personal (rather than external) issues. Implementation of CM in Russia should focus on empowerment and support in addressing both personal and system factors such as stigmatization. Programs need to consider strategies to overcome barriers such as poormotivation. Financial support: Funded by NIDA, R01DA032082, R01DA032082-03S1. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.374 Intrinsic clustering of treatment outcome in recovery from opioid use disorder: Results from starting treatment with agonist replacement therapies Sean Luo1, Jeffery Goldsmith1, Richard Crist3, Wade Berritini3, Andrew Saxon4, Walter Ling5, Maureen P. Hillhouse2, Edward V. Nunes1 1 Columbia University, New York, NY, United States 2 Integrated Substance Abuse Programs, University of California, Los Angeles, Los Angeles, CA, United States 3 Psychiatry, University of Pennsylvania, Philadelphia, PA, United States 4 Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States 5 UCLA, Integrated Substance Abuse, Los Angeles, CA,

Sending me up, sending me down

Sending me up, sending me down

Intranasal Insulin to Treat and Protect Against Posttraumatic Stress Disorder

Lessons learned from research on the treatment of Alzheimer’s disease (AD) suggest a new strategy for treating posttraumatic stress disorder (PTSD). The NIH recently selected intranasal insulin as a promising treatment for AD and committed 7.9 million in funding to further test it nationally (Health and Human Services Press Office for Secretary Kathleen Sebelius, 2012). The noninvasive intranasal method for bypassing the blood-brain barrier to target therapeutics (including insulin) to the brain to treat neurodegenerative disorders such as AD and stroke was first discovered in 1989 (Frey, 1991) and was later described specifically for the use of intranasal insulin to target the brain to treat AD and certain other CNS disorders (Frey, 2001). Intranasal therapeutics bypass the blood-brain barrier and rapidly reach the brain by traveling extracellularly along the olfactory and trigeminal neural pathways (Lochhead and Thorne, 2012). This increases efficacy while reducing systemic exposure and unwanted side effects. Intranasal insulin treatment improves memory in healthy adults, with no change in the blood levels of insulin or glucose (Benedict et al., 2004). Researchers in Germany conducted several additional human clinical trials showing that intranasal insulin improves memory in healthy adults (Benedict et al., 2011). In 2006, Dr Suzanne Craft, at the University of Washington and the Veterans Affairs Puget Sound Health Care System, and colleagues (of whom I was one) reported that intranasal insulin improved memory in only 20 minutes after a single intranasal insulin treatment in patients with AD (Reger et al., 2006). Intranasal insulin (twice a day) also improved memory, attention, and functioning in patients with AD during a 21-day period (Reger et al., 2008) and improved memory and general cognition and reduced loss of brain fludeoxyglucose uptake in patients with AD or amnestic mild cognitive impairment treated with intranasal insulin in a 4-month clinical trial, with no change in the blood levels of insulin or glucose (Craft, 2012). It is not surprising that intranasal insulin is an effective treatment of AD because glucose uptake and use are significantly decreased in patients with AD (de Leon et al., 1997). Glucose is the only source of energy used by brain cells under normal conditions, and the brain cells of patients with AD are starved for energy. AD has been reported to involve a deficiency of insulin and insulin signaling in the brain (Steen et al., 2005.) Type 2 diabetes is a major risk factor for developing AD. Intranasal insulin is far more than simply a treatment of AD symptoms. When intranasal insulin reaches the brain, it stimulates the formation of insulin-degrading enzyme, which is capable of degrading beta amyloid, one of the principal abnormal proteins known to accumulate in the brains of patients with AD. Further, the activity of glycogen-synthase kinase-3-beta, the enzyme that phosphorylates tau to create AD neurofibrillary tangles, has been reported to be downregulated in response to insulin. Finally, insulin receptor signaling increases synaptic density, and loss of synapses is key to the neuropathology of AD (Benedict et al., 2011). Stress has also been found to reduce the uptake and use of glucose by brain cells. In 1986, Sapolsky reported that glucocorticoids released in response to stress could damage neurons in the hippocampus. Multiple mechanisms are likely involved in this action, one of which is the inhibition of glucose use in the hippocampus by glucocorticoids. Cortisol has been reported to reduce hippocampal glucose use in healthy elderly adults on the basis of examination of the brain glucose use (cerebral metabolic rate of glucose consumption) response to hydrocortisone (cortisol; de Leon et al., 1997). It is likely that glucocorticoids also reduce the capacity of the hippocampus to survive neurological insults because glucocorticoids inhibit glucose transport 15% to 30% in both primary and secondary hippocampal astrocytic cultures, and this could impair the ability of astrocytes to aid neurons by removing damaging glutamate from the synapse during times of neurological crisis (Virgin et al., 1991). Glucocorticoids released in response to major stress inhibit local cerebral glucose use throughout the brain and inhibit glucose transport in neurons; glia; and, possibly, endothelial cells in vitro (Sapolsky et al., 2000). Baker et al. (2005) have reported that mean CSF cortisol concentrations are significantly higher in combat veterans with PTSD than in healthy comparison subjects. Concentrations of CSF COMMENTARY

Hearing aid effectiveness after aural rehabilitation: Individual versus group trial results

We designed this noninferiority randomized trial to determine (1) if group hearing aid fitting visits and group hearing aid follow-up visits were at least as effective as individual visits in terms of hearing-related function (measured with the Inner Effectiveness of Auditory Rehabilitation [EAR] scale) and adherence, and (2) if group visits were less costly over the 6 mo post-fitting period. For 644 participants randomized to receive their hearing aid visits in an individual or group format at the Department of Veterans Affairs Puget Sound Health Care System, 6 mo outcomes showed no significant differences in Inner EAR scores between individual and group fitting (p = 0.53) or follow-up (p = 0.11), or in the number of hours per day hearing aids were worn between individual and group fitting (p = 0.90) or follow-up (p = 0.24). We found significantly higher cost for individual compared with group fitting (p < 0.001) and follow-up (p < 0.001). We conclude that outcomes for group hearing aid fitting and hearing aid follow-up visits were not inferior to individual hearing aid fitting and follow-up visits, with group fitting and follow-up visits yielding cost savings.