Performance of Impulse Oscillometry in Identifying Restrictive Lung Defects in a Veteran Cohort.

Background: Impulse oscillometry (IOs) is a technique used to evaluate lung function that uses sound waves imposed over tidal breathing to characterize the airways and lung parenchyma. IOs has been particularly useful in the identification of obstructive lung defects. The present analysis seeks to explore the use of IOs in the identification of restrictive lung physiology among a group of Gulf War I veterans exposed to depleted uranium (DU). Methods: A total of 36 out of a dynamic 85-veteran cohort attended in-person surveillance visits in 2019 and completed both IOs and PFTs. Performance on IOs was evaluated in a cross-sectional analysis of the group overall and in those identified as having restrictive lung defects defined by either spirometry (FEV1/FVC ≥ LLN and FVC < LLN) or lung volumes (TLC < LLN). Results: A total of 6 individuals were identified as having restriction (4 based on spirometry alone and an additional 2 by lung volumes). When restriction was present, IOs values of both resistance and reactance were significantly more abnormal. Conclusion: In the assessment of lung function, IOs may be advantageous over PFTs because it is faster to perform and effort-independent. Although little is known about the utility of IOs in identifying restrictive lung physiology, our results support its use.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

Respiratory Health Associated With Systemic Metal Exposure in Post-9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to veterans without elevated metals, those with elevated metals had had higher FEV 1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post-9/11 veterans are not associated with adverse respiratory health outcomes.

Feasibility and acceptability of continuous identity cognitive therapy as a recovery-oriented suicide treatment for Veterans: A study protocol.

Background: Suicide is a leading cause of death among Veterans, with rates significantly higher than the general population. To address this issue, it is crucial to develop and implement more effective treatments for Veterans with suicidal thoughts and/or behaviors, particularly those in the post-acute suicidal episode (PASE) stage. The present study aims to establish the feasibility and acceptability of a novel, recovery-oriented treatment called Continuous Identity Cognitive Therapy (CI-CT) for PASE Veterans. Methods: This 3-year open-label pilot study will include three one-arm trials and a pilot randomized controlled trial (RCT). A total of 57 Veterans with a history of an acute suicidal episode within the previous year will be recruited. Primary outcome measures will include changes in personal recovery, suicidal thoughts, and behaviors. Secondary outcomes will include changes in self-identity, life satisfaction, and hopefulness. Feasibility and acceptability will be assessed through attendance and retention rates, drop-out rates, and client satisfaction. Conclusion: This study aims to develop and evaluate the feasibility and acceptability of a novel recovery-oriented intervention for Veterans experiencing PASE. If the intervention is found to be feasible and acceptable, a manualized version will be finalized and a large-scale multi-site RCT will be designed to assess its clinical efficacy on a broader Veteran population. The results of this trial will aid in the development of effective treatment and provide valuable insights into the preliminary feasibility, acceptability, and effectiveness of this approach in reducing suicidal thoughts and behaviors and promoting recovery and rehabilitation in this population.

Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

Social functioning mediates the relationship between psychiatric symptoms and recovery among veteran and community service users with serious mental illness.

OBJECTIVE: Previous research has established the impact of psychiatric symptoms on social functioning, while there is a paucity of research examining how social functioning relates to personal recovery, an individual's self-assessment of their mental health recovery. This study examined the mediating effect of social engagement, interpersonal communication, and satisfaction with support in the relationship between distinct psychiatric symptom clusters and perceived mental health recovery. METHODS: In a cross-sectional study, both patient self-report and provider assessment data were collected for 250 patients with serious mental illness (SMI) across four mental health service sites. Parallel mediation analytic models were used. RESULTS: Interpersonal communication partially mediated the relationship between positive and negative symptom clusters and personal recovery. Satisfaction with social supports partially mediated the relationship between excited symptoms and personal recovery. Both interpersonal communication and satisfaction with social supports partially mediated the relationship between general psychological distress and depressive symptoms and personal recovery. Collectively, social functioning mediators explained nearly half of the relationship between general psychological distress and excited symptoms and personal recovery and nearly all of the relationship between positive symptoms and personal recovery. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Clinical providers working with persons with SMI should regularly assess social functioning in addition to assessing psychiatric symptoms and personal recovery factors and should incorporate social skills education into SMI group and individual treatments. Social functioning as a target of treatment may be especially beneficial for patients who are dissatisfied with other interventions or feel they have experienced the maximum benefit from treatment and are seeking additional methods to support personal recovery. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Even mild internalized stigma merits attention among adults with serious mental illness.

Internalized or self-stigma can be damaging to psychological and social functioning and recovery, especially for people with serious mental illness. Most studies have focused on the effects of high self-stigma, which has included both moderate and high self-stigma, versus low levels of self-stigma which has included no, minimal, or mild self-stigma. Therefore, little is known about the variation within these categories (e.g., minimal versus mild self-stigma) and its impact on recovery. This article examines differences in the demographic, clinical, and psychosocial variables associated with different levels of self-stigma severity. Baseline data (N = 515) from two concurrent randomized controlled trials of a psychosocial intervention aimed at reducing internalized stigma, and its effects among adults with serious mental illnesses were examined. We found that participants with greater psychological sense of belonging, and greater perceived recovery were significantly less likely to have mild or moderate/high internalized stigma than minimal stigma. Those reporting a greater frequency of stigma experiences, however, were more likely to have mild or moderate/high internalized stigma than minimal stigma. Our findings further underscore the multifaceted nature and impact of self-stigma, particularly in interpersonal relationships and interactions, and demonstrate the importance of attending to even mild levels of self-stigma endorsement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Increasing social and community participation in veterans living with schizophrenia: A treatment outcome study.

People living with schizophrenia often face challenges engaging in social and community activities. A critical barrier is negative symptoms that reflect diminished feelings and thoughts that support social interaction. Several years ago, we began a process of specifying an intervention for individuals with schizophrenia and clinically meaningful negative symptoms that could be delivered in an integrated fashion with mental health services offered in VA medical centers with the primary focus of improving social and community engagement. In the present study, we examined the impact of a multi-component intervention to improve social and community participation in a group of Veterans living with schizophrenia and negative symptoms. We compared an intervention called Engaging in Community Roles and Experiences (EnCoRE) - a 12-week program of individual and group meetings that support learning and implementing skills with the goal of helping participants increase engagement in personally-relevant social and community activities - to an active wellness education control condition. Participants in both conditions attended on average of at least half of the groups that were offered, indicating that many individuals living with negative symptoms are willing to participate in an intervention to improve social and community participation. Although there were no significant differences on the two primary outcomes, those in EnCoRE showed better social and general functioning at post treatment and improved social motivational negative symptoms and decreases in perceived limitations at a 3-month follow-up. EnCoRE may be especially beneficial for participants who endorsed more dysfunctional attitudes about their abilities.

Self-reported respiratory outcomes associated with blast exposure in post 9/11 veterans.

BACKGROUND: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001. We studied whether veterans who experienced blast exposure report more chronic respiratory symptoms and diagnoses compared to deployed veterans who did not. METHODS: 9,000 veterans included in the Department of Veterans Affairs Toxic Embedded Fragment Registry were invited to complete a survey assessing chronic respiratory symptoms, diagnoses, and exposures. Blast exposure was assessed using the Brief Traumatic Brain Injury Screen and by presence of other symptoms such as blast-induced loss of consciousness. RESULTS: Participants (n = 2147) were predominantly <40 years old, served in the Army, and injured on average 12.8 years previously. 91% reported blast exposure. Blast-exposed veterans were significantly more likely to report cough (OR 1.8), wheeze (OR 2.4), and dyspnea (OR 1.8), even after adjustment for covariates including smoking and occupational exposures to dust, fume, and gas. Veterans reporting higher severity of blast impact, such as traumatic brain injury or loss of consciousness, were more likely to report cough, wheeze, or dyspnea. Veterans with higher severity of blast impact by multiple measures were also more likely to report having COPD. Those reporting a physician-diagnosis of traumatic brain injury were significantly more likely to report having both asthma (OR 1.5) and COPD (OR 1.5). CONCLUSIONS: Blast exposure is associated with respiratory symptoms and COPD. Respiratory system evaluation may warrant inclusion as a standard part of barotrauma health assessment.

A randomized, double-blind, placebo-controlled, pharmacogenetic study of ondansetron for treating alcohol use disorder.

BACKGROUND: In a previous study, ondansetron, a serotonin 5-HT3 receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants with moderate-to-severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5-HT3A (HTR3A), and 5-HT3B (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron-treated individuals with population-specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B. METHODS: In this 16-week, double-blind, placebo-controlled, parallel-group clinical trial, adults with AUD were randomized to receive low-dose oral ondansetron (0.33 mg twice daily) or placebo stratified by "responsive" versus "nonresponsive" genotype defined using population-specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent-to-treat analysis were used to compare the treatment groups on the primary outcome-DPDD-and two secondary outcomes-heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment. RESULTS: Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent-to-treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study-related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems. CONCLUSIONS: We found no evidence that low-dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions.

Development and evaluation of a structured guide to assess the preventability of hospital-onset bacteremia and fungemia.

OBJECTIVE: To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks. DESIGN: HOB preventability rating guide was compared against a reference standard expert panel. PARTICIPANTS: A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison. METHODS: The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories: preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among ≥70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the κ (kappa) statistic. RESULTS: Expert panel consensus criteria were met for 52 scenarios (63%) after 2 rounds.After 2 rounds, guide-based rating matched expert panel consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewers 1 and 2, respectively. Agreement rates between the 2 reviewers were 84% overall (κ, 0.76; 95% confidence interval [CI], 0.64-0.88]) and 87% (κ, 0.79; 95% CI, 0.65-0.94) for the 52 scenarios with expert consensus. CONCLUSIONS: Preventability ratings of HOB scenarios by 2 reviewers using a rating guide matched expert consensus in most cases with moderately high interreviewer reliability. Although diversity of expert opinions and uncertainty of preventability merit further exploration, this is a step toward standardized assessment of HOB preventability.

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder.

OBJECTIVE ­: Psychiatric hospitalizations and emergency department (ED) visits are costly, stigmatizing, and often ineffective. Given the immune and kynurenine activation in bipolar disorder (BD) and schizophrenia, as well as the immune-modulatory effects of statins, we aimed to compare the relative risk (RRs) of psychiatric hospitalizations and ED visits between individuals prescribed lipophilic vs. hydrophilic statins vs. no statins. We hypothesized (a) reduced rates of hospitalization and ER utilization with statins versus no statins and (b) differences in outcomes between statins, as lipophilia increases the capability to penetrate the blood-brain barrier with potentially beneficial neuroimmune, antioxidant, neuroprotective, neurotrophic, and endothelial stabilizing effects, and, in contrast, potentially detrimental decreases in brain cholesterol concentrations leading to serotoninergic dysfunction, changes in membrane lipid composition, thus affecting ion channels and receptors. METHODS ­: We used VA service utilization data from October 1, 2010 to September 30, 2015. The RRs for psychiatric hospitalization and ED visits, were estimated using robust Poisson regression analyses. The number of individuals analyzed was 683,129. RESULTS ­: Individuals with schizophrenia and BD who received prescriptions for either lipophilic or hydrophilic statins had a lower RR of psychiatric hospitalization or ED visits relative to nonstatin controls. Hydrophilic statins were significantly associated with lower RRs of psychiatric hospitalization but not of ED visits, compared to lipophilic statins. CONCLUSION ­: The reduction in psychiatric hospitalizations in statin users (vs. nonusers) should be interpreted cautiously, as it carries a high risk of confounding by indication. While the lower RR of psychiatric hospitalizations in hydrophilic statins relative to the lipophilic statins is relatively bias free, the finding bears replication in a specifically designed study. If replicated, important clinical implications for personalizing statin treatment in patients with mental illness, investigating add-on statins for improved therapeutic control, and mechanistic exploration for identifying new treatment targets are natural next steps.

Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs.

OBJECTIVE: Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system. METHODS: This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group. RESULTS: In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine. CONCLUSIONS: In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

A Derivative of the D5 Monoclonal Antibody That Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2-Neutralizing Activity.

HIV-1 infection is initiated by the viral glycoprotein Env, which, after interaction with cellular coreceptors, adopts a transient conformation known as the prehairpin intermediate (PHI). The N-heptad repeat (NHR) is a highly conserved region of gp41 exposed in the PHI; it is the target of the FDA-approved drug enfuvirtide and of neutralizing monoclonal antibodies (mAbs). However, to date, these mAbs have only been weakly effective against tier-1 HIV-1 strains, which are most sensitive to neutralizing antibodies. Here, we engineered and tested 11 IgG variants of D5, an anti-NHR mAb, by recombining previously described mutations in four of D5's six antibody complementarity-determining regions. One variant, D5_AR, demonstrated 6-fold enhancement in the 50% inhibitory dose (ID50) against lentivirus pseudotyped with HXB2 Env. D5_AR exhibited weak cross-clade neutralizing activity against a diverse set of tier-2 HIV-1 viruses, which are less sensitive to neutralizing antibodies than tier-1 viruses and are the target of current antibody-based vaccine efforts. In addition, the neutralization potency of D5_AR IgG was greatly enhanced in target cells expressing FcγRI, with ID50 values of <0.1 µg/ml; this immunoglobulin receptor is expressed on macrophages and dendritic cells, which are implicated in the early stages of HIV-1 infection of mucosal surfaces. D5 and D5_AR have equivalent neutralization potency in IgG, Fab, and single-chain variable-fragment (scFv) formats, indicating that neutralization is not impacted by steric hindrance. Taken together, these results provide support for vaccine strategies that target the PHI by eliciting antibodies against the gp41 NHR and support investigation of anti-NHR mAbs in nonhuman primate passive immunization studies. IMPORTANCE Despite advances in antiretroviral therapy, HIV remains a global epidemic and has claimed more than 32 million lives. Accordingly, developing an effective HIV vaccine remains an urgent public health need. The gp41 N-heptad repeat (NHR) of the HIV-1 prehairpin intermediate (PHI) is highly conserved (>90%) and is inhibited by the FDA-approved drug enfuvirtide, making it an attractive vaccine target. However, to date, anti-NHR antibodies have not been potent. Here, we engineered D5_AR, a more potent variant of the anti-NHR antibody D5, and established its ability to inhibit HIV-1 strains that are more difficult to neutralize and are more representative of circulating strains (tier-2 strains). The neutralizing activity of D5_AR was greatly potentiated in cells expressing FcγRI; FcγRI is expressed on cells that are implicated at the earliest stages of sexual HIV-1 transmission. Taken together, these results bolster efforts to target the gp41 NHR and the PHI for vaccine development.

A Multicenter Evaluation of Probiotic Use for the Primary Prevention of Clostridioides difficile Infection.

BACKGROUND: Primary prevention of Clostridioides difficile infection (CDI) is a priority for hospitals. Probiotics have the potential to interfere with colonization and CDI. In this study, we evaluated the impact of a computerized clinical decision support (CCDS) tool to prescribe probiotics for primary prevention of CDI among adult hospitalized patients. METHODS: A CCDS tool was implemented into the electronic medical record at 4 hospitals to prompt prescription of a probiotic preparation at the time of antibiotic prescription in high-risk patients in May 2019. Interrupted time series using segmented regression analysis was conducted to evaluate hospital-wide CDI incidence for the year pre- and post-CCDS implementation. In addition, multivariable logistic regression was used to evaluate CDI incidence in patients who qualified for probiotics in the pre- vs post-intervention periods, adjusting for potential confounders. To adjust for potential differences in patients who received probiotics in the post-intervention period, propensity score-matched pairs were developed to evaluate CDI risk by receipt of probiotics. RESULTS: Quarterly CDI incidence increased over time post-intervention relative to baseline trends (slope change, 1.4; 95% confidence interval [CI], .9-1.9). The odds ratio (OR) of CDI was 1.41 in eligible patients post-intervention compared with pre-intervention (adjusted OR, 1.41; 95% CI, 1.11-1.79). Propensity score-matched analysis showed that patients who received probiotics did not have lower rates of CDI compared with those who did not receive probiotics (OR, 1.46; 95% CI, .87-2.45). CONCLUSIONS: Use of probiotics for primary prevention of CDI among adult inpatients receiving antibiotics is not supported.

Surveillance of Depleted Uranium-exposed Gulf War Veterans: More Evidence for Bone Effects.

ABSTRACT: Gulf War I veterans who were victims of depleted uranium (DU) "friendly-fire" incidents have undergone longitudinal health surveillance since 1994. During the spring of 2019, 36 members of the cohort were evaluated with a monitoring protocol including exposure assessment for total and isotopic uranium concentrations in urine and a comprehensive review of health outcomes, including measures of bone metabolism and bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained depleted uranium (DU) shrapnel fragments. In addition, a measure of bone resorption, N-telopeptide, showed a statistically significant increase in those in the high DU subgroup, a finding consistent with a statistically significant decrease in bone mass also observed in this high DU subgroup compared to the low DU subgroup. After more than 25 y since first exposure to DU, an aging cohort of military veterans continues to show few U-related health effects in known target organs of U toxicity. The new finding of impaired BMD in the high DU subgroup has now been detected in two consecutive surveillance visits. While this is a biologically plausible uranium effect, it is not reflected in other measures of bone metabolism in the full cohort, which have largely been within normal limits. However, ongoing accrual of the U burden from fragment absorption over time and the effect of aging further impairing BMD suggest the need for future surveillance assessments of this cohort.

Support for the social-cognitive model of internalized stigma in serious mental illness.

One prominent social-cognitive model of internalized stigma by Corrigan and his colleagues (2012; 2002) proposes that individuals are exposed to societal stereotypes about mental illness, at least tacitly agree with them, and may apply them to oneself, engendering harmful self-beliefs. There is limited empirical support for this model in serious mental illness. Moreover, it is not clearly established how internalized stigma and its associated factors impact recovery in this population. The current study uses structural equation modeling (SEM) to assess the social-cognitive model's goodness of fit in a sample of Veterans with serious mental illness (Veteran sample, n = 248), and then validates the model in a second and independent sample of individuals receiving community-based psychiatric rehabilitation services (community sample, n = 267). Participants completed the Self-Stigma of Mental Illness Scale (SSMIS; Corrigan et al., 2006) and measures of self-esteem, self-efficacy, and recovery attitudes. Consistent with Corrigan and colleagues' formulation of internalized stigma, SEM analyses showed a significant indirect pathway from stereotype awareness, to stereotype agreement, to application to self, to self-esteem decrement, to poorer recovery attitudes. Additionally, there was a significant direct effect from stereotype awareness to self-esteem. This study shows that individuals with serious mental illness experience psychological harm from stigma in two ways: (1) through perceived public prejudice and bias, and (2) through internalizing these negative messages. In particular, stigma harms individuals' self-esteem, which then reduces their recovery attitudes.

Impact of a C. difficile infection (CDI) reduction bundle and its components on CDI diagnosis and prevention.

BACKGROUND: Published bundles to reduce Clostridioides difficile Infection (CDI) frequently lack information on compliance with individual elements. We piloted a computerized clinical decision support-based intervention bundle and conducted detailed evaluation of several intervention-related measures. METHODS: A quasi-experimental study of a bundled intervention was performed at 2 acute care community hospitals in Maryland. The bundle had five components: (1) timely placement in enteric precautions, (2) appropriate CDI testing, (3) reducing proton-pump inhibitor (PPI) use, (4) reducing high-CDI risk antibiotic use, and (5) optimizing use of a sporicidal agent for environmental cleaning. Chi-square and Kruskal-Wallis tests were used to compare measure differences. An interrupted time series analysis was used to evaluate impact on hospital-onset (HO)-CDI. RESULTS: Placement of CDI suspects in enteric precautions before test results did not change. Only hospital B decreased the frequency of CDI testing and reduced inappropriate testing related to laxative use. Both hospitals reduced the use of PPI and high-risk antibiotics. A 75% decrease in HO-CDI immediately postimplementation was observed for hospital B only. CONCLUSION: A CDI reduction bundle showed variable impact on relevant measures. Hospital-specific differential uptake of bundle elements may explain differences in effectiveness, and emphasizes the importance of measuring processes and intermediate outcomes.

Effect of Body Refrigeration Time on Cornea Donor Tissue.

PURPOSE: To determine how early body refrigeration affects corneal donor transplant suitability and endothelial cell density. METHODS: Donor information was obtained from the CorneaGen Eye Bank including demographics, time of death to preservation, and body refrigeration status, for donors between 2012 and 2016. The death to preservation interval was classified into 3 categories: 0 to 10, 10 to 20, and 20+ hours. Two primary logistic method models were fit using a main effects model and an interaction model to determine the association of body refrigeration on unsuitability of transplantation and endothelial cell density. RESULTS: Analysis was from 42,929 donor eyes, with a mean (standard deviation) endothelial cell count of 2743 (415) cells/mm2. Fifty-nine percent of donor eyes were from male donors in the eye bank data set, and the mean death to preservation interval was 11.0 (5.6) hours for all eyes. Unsuitability for transplantation demonstrated a reduced adjusted odds ratio by 22% (OR = 0.78, P = 0.009) when the body was refrigerated during the death to preservation interval versus when the body was not refrigerated. Eyes that were refrigerated, however, exhibited no statistically significant difference in endothelial cell count from eyes that were not refrigerated (P = 0.12). CONCLUSIONS: We demonstrate an appreciable effect of early body refrigeration on transplant suitability in this large cohort of eye bank eyes. There was no beneficial effect of body refrigeration on endothelial cell count.