Racial differences in odds of asthma exacerbations among Aspergillus fumigatus-sensitized adults with asthma.

BACKGROUND: Allergic sensitization to mold is a risk factor for poor asthma outcomes, but whether it accounts for disparities in asthma outcomes according to race or socioeconomic status is not well-studied. OBJECTIVE: To identify factors associated with allergic sensitization to molds and evaluate associations of sensitization to molds with asthma exacerbations after stratifying by race. METHODS: We conducted a retrospective cohort study of adults with asthma who had an outpatient visit to a large health system between January 1, 2017 and June 30, 2023 and received aeroallergen testing to Aspergillus fumigatus, Penicillium, Alternaria, and Cladosporium. We used logistic regression models to evaluate factors associated with mold sensitization and the effect of mold sensitization on asthma exacerbations in the 12 months before testing, overall and then stratified by race. RESULTS: A total of 2732 patients met the inclusion criteria. Sensitization to each mold was negatively associated with being a woman (odds ratios [ORs] ≤ 0.59, P ≤ .001 in 5 models) and positively associated with the Black race (ORs ≥ 2.16 vs White, P < .0005 in 5 models). In the full cohort, sensitization to molds was not associated with asthma exacerbations (ORs = 0.95-1.40, P ≥ .003 in 5 models and all above the corrected P value threshold). Among 1032 Black patients, sensitization to A fumigatus, but not to other molds, was associated with increased odds of asthma exacerbations (OR = 2.04, P < .0005). CONCLUSION: Being a man and Black race were associated with allergic sensitization to molds. Sensitization to A fumigatus was associated with asthma exacerbations among Black patients but not the overall cohort, suggesting that A fumigatus allergy is a source of disparities in asthma outcomes according to race.

Trust and virtual communication during the COVID-19 pandemic for adults with asthma from low-income neighborhoods: What have we learned?

BACKGROUND: Low-income and marginalized adults disproportionately bear the burden of poor asthma outcomes. One consequence of the structural racism that preserves these inequities is decreased trust in government and health care institutions. OBJECTIVE: We examined whether such distrust extended to health care providers during the pandemic. METHODS: We enrolled adults living in low-income neighborhoods who had required a hospitalization, an emergency department visit, or a prednisone course for asthma in the prior year. Trust was a dichotomized measure derived from a 5-item questionnaire with a 5-point Likert scale response. The items were translated to the binary variable "strong" versus "weak" trust. Communication was measured using a 13-item questionnaire with a 5-point Likert scale. Logistic regression was used to examine the association between communication and trust, controlling for potential confounders. RESULTS: We enrolled 102 patients, aged 18 to 78 years; 87% were female, 90% were Black, 60% had some post-high school education, and 57% were receiving Medicaid. Of the 102 patients, 58 were enrolled before the March 12, 2020, pandemic start date, and 70 (69%) named doctors as their most trusted source of health information. Strong trust was associated with a negative response to the statement "It is hard to reach a person in my doctor's office by phone." There was no evidence of an association between the overall communication scores and trust. Satisfaction with virtual messaging was weaker among those with less trust. CONCLUSIONS: These patients trust their physicians, value their advice, and need to have accessible means of communication.

Racial and Ethnic Disparities in Appropriate Thyroid Cancer Treatment, Before and After the Release of the 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines reduced the recommended extent of therapy for low-risk thyroid cancers. Little is known about the impact of these changes on overall treatment patterns and on previously described racial/ethnic disparities in guideline-concordant care. This study aimed to assess trends in thyroid cancer care before and after release of the 2015 guidelines, with particular attention to racial/ethnic disparities. METHODS: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2018). An interrupted time series design was used to assess trends in treatment before and after the 2015 guidelines. Appropriateness of surgical and radioactive iodine (RAI) treatment was determined based on the ATA guidelines, and the likelihood of receiving guideline-concordant treatment was compared between racial/ethnic groups. RESULTS: The study identified 309,367 patients (White 74%, Black 8%, Hispanic 9%, Asian 6%). Between 2010 and 2015, the adjusted probability of appropriate surgery was lower for Black (- 2.1%; p < 0.001), Hispanic (- 1.0%; p < 0.001), and Asian (- 2.1%; p < 0.001) patients than for White patients. After 2015, only Hispanic patients had a lower probability of undergoing appropriate surgical therapy (- 2.6%; p = 0.040). Similarly, between 2010 and 2015, the adjusted probability of receiving appropriate RAI therapy was lower for the Hispanic (- 3.6%; p < 0.001) and Asian (- 2.4%; p < 0.001) patients than for White patients. After 2015, the probability of appropriate RAI therapy did not differ between groups. CONCLUSIONS: Between 2010 and 2015, patients from racial/ethnic minority backgrounds were less likely than White patients to receive appropriate surgical and RAI therapy for thyroid cancer. After the 2015 guidelines, racial/ethnic disparities in treatment improved.

Do Placebos Primarily Affect Subjective as Opposed to Objective Measures? A Meta-Analysis of Placebo Responses in Insomnia RCTs.

INTRODUCTION: Little is known about the relative magnitude of placebo responses on objective and subjective measures of sleep continuity. To address this issue, the pre-post effects of placebos on objective and subjective measures (i.e., polysomnography [PSG] and sleep diaries) were evaluated meta-analytically. The guiding hypothesis was that large responses would be observed on sleep diary measures and small responses would be observed on PSG measures. METHODS: PubMed searches, 1967-2016, yielded 329 possible articles, 17 of which met the inclusion and exclusion criteria for the present analysis (including 879 subjects with PSG data, 1,209 subjects with diary data, and six studies with both PSG and sleep diary data). Average change and weighted effect sizes (ESs) were computed via modeling for sleep latency (SL), wake after sleep onset (WASO) and total sleep time (TST). RESULTS: Pre-to-post change on PSG measures were: SL -13.7 min., ES = -0.37; WASO -14.3 min., ES = -0.36; and TST 29.8 min., ES = 0.50. Pre-to-post change on sleep diary measures were: SL -13.5 min., ES = -0.36; WASO -13.3 min., ES = -0.20; and TST 25.5 min., ES = 0.36. The modeled average objective subjective difference per sleep continuity measure was less than 5 minutes. The modeled average objective subjective difference per sleep continuity measure (in effect sizes) was less than 0.17. DISCUSSION: The observed outcomes of this analysis suggest that placebos produce comparable effects on objective and subjective measures of sleep continuity. Thus, objective measures do not appear to protect against placebo responses. This being the case and given the importance of the subjective experience of illness severity and recovery, such data suggests that prospectively sampled sleep continuity data (sleep diaries) may be the optimal data for clinical trials, particularly when only one measure is possible.

Standardized Cesarean Risk Counseling with Induction: Impact on Racial Disparities in Birth Satisfaction.

OBJECTIVE: Our prior work demonstrated decreased birth satisfaction for Black women undergoing labor induction. We aimed to determine if implementation of standardized counseling around calculated cesarean risk during labor induction could reduce racial disparities in birth satisfaction. STUDY DESIGN: We implemented use of a validated calculator that provides an individual cesarean risk score for women undergoing induction into routine care. This prospective cohort study compared satisfaction surveys for 6 months prior to implementation (preperiod: January 2018-June 2018) to 1 year after (postperiod: July 2018-June 2019). Women with full-term (≥37 weeks) singleton gestations with intact membranes and an unfavorable cervix undergoing induction were included. In the postperiod, providers counseled patients on individual cesarean risk at the beginning of induction using standardized scripts. This information was incorporated into care at patient-provider discretion. The validated 10-question Birth Satisfaction Scale-Revised (BSS-R) subdivided into three domains was administered throughout the study. Patients were determined to be "satisfied" or "unsatisfied" if total BSS-R score was above or below the median, respectively. In multivariable analysis, interaction terms evaluated the differential impact of the calculator on birth satisfaction by race (Black vs. non-Black women). RESULTS: A total of 1,008 of 1,236 (81.6%) eligible women completed the BSS-R (preperiod: 330 [79.7%] versus postperiod: 678 [82.5%], p = 0.23), 63.8% of whom self-identified as Black. In the preperiod, Black women were 50% less likely to be satisfied than non-Black women, even when controlling for differences in parity (Black: 39.0% satisfied vs. non-Black: 53.9%, adjusted odds ratio [aOR] = 0.49, 95% confidence interval [CI]: 0.30-0.79). In the postperiod, there was no difference in satisfaction by race (Black: 43.7% satisfied vs. non-Black: 44.0%, aOR = 0.97. 95% CI: 0.71-1.33). Therefore, disparities in birth satisfaction were no longer present at postimplementation (interaction p = 0.03). CONCLUSION: Implementation of standardized counseling with a validated calculator to predict cesarean risk after labor induction is associated with a decrease in racial disparities in birth satisfaction. KEY POINTS: · Preintervention, Black women were less likely to have above-median birth satisfaction.. · We implemented standardized counseling around cesarean risk with labor induction.. · Implementation was associated with reduced racial disparities in birth satisfaction scores..

Predictive Validity of a Computerized Battery for Identifying Neurocognitive Impairments Among Children Living with HIV in Botswana.

Children living with HIV (HIV+) experience increased risk of neurocognitive deficits, but standardized cognitive testing is limited in low-resource, high-prevalence settings. The Penn Computerized Neurocognitive Battery (PennCNB) was adapted for use in Botswana. This study evaluated the criterion validity of a locally adapted version of the PennCNB among a cohort of HIV+ individuals aged 10-17 years in Botswana. Participants completed the PennCNB and a comprehensive professional consensus assessment consisting of pencil-and-paper psychological assessments, clinical interview, and review of academic performance. Seventy-two participants were classified as cases (i.e., with cognitive impairment; N = 48) or controls (i.e., without cognitive impairment; N = 24). Sensitivity, specificity, positive predictive value, negative predictive value, and the area under receiver operating characteristic curves were calculated. Discrimination was acceptable, and prediction improved as the threshold for PennCNB impairment was less conservative. This research contributes to the validation of the PennCNB for use among children affected by HIV in Botswana.

Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia.

BACKGROUND: Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL. PROCEDURE: This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose <60 mg/dL. Cox regression was used to evaluate the association with age and identify other potential risk factors. RESULTS: We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age = 0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity = 3.50; 95% CI, 1.47-8.36). CONCLUSIONS: Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children.

Primary language and the electronic health record patient portal: Barriers to use among Spanish-speaking adults with asthma.

OBJECTIVES: To assess electronic health record patient portal use among Spanish-speaking patients with asthma compared to English-speaking patients and identify barriers to use. METHODS: Using data collected for a PCORI-funded randomized controlled trial to increase patient portal use in low-income adults with uncontrolled asthma, we estimated the association between portal use, measured using surveys and actual user login data, and primary language. Open-ended survey responses were grouped into common themes. RESULTS: Among 301 adults with asthma: age 18-87, 90% female, 17% Spanish speakers; 44% had no portal use during the study. Spanish speakers were less likely to have ever heard of the patient portal than English speakers (p=.001) and reported more difficulty navigating the portal (p<.001). Spanish speakers with low health literacy had less portal use (31%) than their English-speaking counterparts (51%) (p=.02). Compared to high-literacy English speakers, the odds of using the portal for low-literacy Spanish speakers were 0.34 (95% CI 0.14, 0.84) (p=.02). Three-quarters of Spanish speakers cited barriers to portal use compared to one-quarter of English speakers, and many suggested creating a Spanish version to improve user-friendliness. CONCLUSIONS: English-only patient portals may not meet the needs of Spanish-speaking patients with uncontrolled asthma. Health systems serving Spanish-speaking communities should implement patient portals in Spanish.

The natural history of insomnia: Does sleep extension differentiate between those that do and do not develop chronic insomnia?

According to the "3P model" of insomnia, the variable that mediates the transition from acute insomnia (AI) to chronic insomnia is "sleep extension" (the behavioural tendency to expand sleep opportunity to compensate for sleep loss). In the present analysis, we sought to evaluate how time in bed (TIB) varies relative to the new onset of AI and chronic insomnia. A total of 1,248 subjects were recruited as good sleepers (GS). Subjects were monitored over 1 year with sleep diaries. State transitions were defined, a priori, for AI, recovered from AI (AI-REC), and for chronic insomnia (AI-CI). Two additional groupings were added based on profiles that were unanticipated: subjects that exhibited persistent poor sleep following AI (AI-PPS [those that neither recovered or developed chronic insomnia]) and subjects that recovered from chronic insomnia (CI-REC). All the groups (GS, AI-REC, AI-CI, AI-PPS and CI-REC) were evaluated for TIB differences with longitudinal mixed effects models. Post hoc analyses for the percentage of the groups that were typed as TIB "restrictors, maintainers, and expanders" were conducted using longitudinal mixed effects models and contingency analyses. Significant differences for pre-post AI TIB were not detected for the insomnia groups. Trends were apparent for the AI-CI group, which suggested that minor increases in TIB occurred weeks before the declared onset of AI. Additionally, it was found that a significantly larger percentage of AI-CI subjects engaged in sleep extension (as compared to GS). The present data suggest that transition from AI to chronic insomnia does not appear to be initiated by sleep extension and the transition may occur before the elapse of 3 months of ≥3 nights of sleep continuity disturbance. Given these findings, it may be that the mismatch between sleep ability and sleep opportunity is perpetuated over time given the failure to "naturally" engage in sleep restriction (as opposed to sleep extension).

Mental Health, Social Influences, and HIV Pre-exposure Prophylaxis (PrEP) Utilization Among Men and Transgender Individuals Screening for HIV Prevention Trials.

The effects of mental health comorbidities and social support on the HIV pre-exposure prophylaxis (PrEP) care continuum are unknown. We conducted a cross-sectional study of men and transgender individuals, ≥ 18 years-old, with ≥ 2 male or transgender partners, or recent condomless anal intercourse. Surveys assessed demographics, mental health treatment, depressive symptomatology, social support, and PrEP-related social contacts. Logistic regression assessed associations between these factors and PrEP uptake and persistence. Participants (n = 247) were 89% cis-male and 46% African-American. Median age was 27 (IQR:23-33). Thirty-seven percent had ever used PrEP, of whom 18% discontinued use. High depressive symptomology was identified in 11% and 9% were receiving mental health treatment. There were no significant associations between depressive symptoms or mental health treatment on the odds of PrEP uptake or discontinuation. Each additional PrEP contact conferred a greater odds of uptake (aOR:1.24, 95% CI: 1.09-1.42). Network-level targets may produce fruitful interventions to increase PrEP uptake.

HIV Infection and Depression Among Opiate Users in a US Epicenter of the Opioid Epidemic.

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder. The prevalence of HIV infection (8.5%) was more than seven times that found in the general population of the city. Eight of the HIV-positive participants (67.0%) reported receiving antiretroviral treatment but almost all of them had unsuppressed virus (87.5%). The majority of participants (57.4%) reported symptoms consistent with major depressive disorder. Severe economic distress (60.3%) and homelessness were common (57%). Polysubstance use was nearly universal, 72.1% had experienced multiple overdoses and prior medication for opioid use disorder (MOUD) treatment episodes (79.9%), but few currently engaged in addiction care. The prevalence, multiplicity and severity of chronic health and socioeconomic problems highlight consequences of the current opioid epidemic and underscore the urgent need to develop integrated models of treatment.

RESUMEN: Utilizando un Centro de Investigación Móvil, inscribimos a 141 usuarios de opioides del vecindario de Filadelfia, un epicentro urbano de la epidemia de opioides. Casi todos (95,6%) cumplieron con los criterios del DSM-5 para el trastorno del uso severo del consumo de opioides. La prevalencia de la infección de VIH (8,5%) fue másﹶ de 7 veces superior a las encontrada en la población general de la ciudad. Ocho de los participantes con VIH positivo (67,0%) reportaron haber recibido tratamiento antirretroviral pero casi todos tuvieron virus no suprimido (87,5%). La mayoría de los participantes (57,4%) informaron síntomas compatibles con el Desorden Depresivo Mayor. La angustia severa por lo económico (60,3%) y las personas sin hogar fueron comunes (57%). El uso de múltiples sustancias fue casi universal, el 721% había experimentado múltiples sobredosis y previos medicamentos para el tratamiento del trastorno por consumo de opioides (MOUD) (79,9%), pero muy pocos estaban comprometidos con la atención a las adicciones. La prevalencia, la multiplicidad y la seriedad de los problemas de salud crónica y los problemas socioeconómicos destacan las consecuencias de la actual epidemia de opioides y subrayan la urgente necesidad de desarrollar nuevos modelos de tratamiento integrados.

NK Response Correlates with HIV Decrease in Pegylated IFN-α2a-Treated Antiretroviral Therapy-Suppressed Subjects.

We previously reported that pegylated IFN-α2a (Peg-IFN-α2a) added to antiretroviral therapy (ART)-suppressed, HIV-infected subjects resulted in plasma HIV control and integrated HIV DNA decrease. We now evaluated whether innate NK cell activity or PBMC transcriptional profiles were associated with decreases in HIV measures. Human peripheral blood was analyzed prior to Peg-IFN-α2a administration (ART, baseline), after 5 wk of ART+Peg-IFN-α2a, and after 12 wk of Peg-IFN-α2a monotherapy (primary endpoint). After 5 wk of ART+Peg-IFN-α2a, immune subset frequencies were preserved, and induction of IFN-stimulated genes was noted in all subjects except for a subset in which the lack of IFN-stimulated gene induction was associated with increased expression of microRNAs. Viral control during Peg-IFN-α2a monotherapy was associated with 1) higher levels of NK cell activity and IFN-γ-induced protein 10 (IP-10) on ART (preimmunotherapy) and 2) downmodulation of NK cell KIR2DL1 and KIR2DL2/DL3 expression, transcriptional enrichment of expression of genes associated with NK cells in HIV controller subjects, and higher ex vivo IFN-α-induced NK cytotoxicity after 5 wk of ART+Peg-IFN-α2a. Integrated HIV DNA decline after immunotherapy was also associated with gene expression patterns indicative of cell-mediated activation and NK cytotoxicity. Overall, an increase in innate activity and NK cell cytotoxicity were identified as correlates of Peg-IFN-α2a-mediated HIV control.

Home visits for uncontrolled asthma among low-income adults with patient portal access.

BACKGROUND: Asthma disproportionately affects low-income and minority adults. In an era of electronic records and Internet-based digital devices, it is unknown whether portals for patient-provider communication can improve asthma outcomes. OBJECTIVE: We sought to estimate the effect on asthma outcomes of an intervention using home visits (HVs) by community health workers (CHWs) plus training in patient portals compared with usual care and portal training only. METHODS: Three hundred one predominantly African American and Hispanic/Latino adults with uncontrolled asthma were recruited from primary care and asthma specialty practices serving low-income urban neighborhoods, directed to Internet access, and given portal training. Half were randomized to HVs over 6 months by CHWs to facilitate competency in portal use and promote care coordination. RESULTS: One hundred seventy (56%) patients used the portal independently. Rates of portal activity did not differ between randomized groups. Asthma control and asthma-related quality of life improved in both groups over 1 year. Differences in improvements over time were greater for the HV group for all outcomes but reached conventional levels of statistical significance only for the yearly hospitalization rate (-0.53; 95% CI, -1.08 to -0.024). Poor neighborhoods and living conditions plus limited Internet access were barriers for patients to complete the protocol and for CHWs to make HVs. CONCLUSION: For low-income adults with uncontrolled asthma, portal access and CHWs produced small incremental benefits. HVs with emphasis on self-management education might be necessary to facilitate patient-clinician communication and to improve asthma outcomes.

Cognitive Behavioral Therapy for Insomnia in Alcohol-Dependent Veterans: A Randomized, Controlled Pilot Study.

BACKGROUND: Insomnia is highly prevalent in individuals recovering from alcohol dependence (AD) and increases their risk of relapse. Two studies evaluating cognitive behavior therapy for insomnia (CBT-I) have demonstrated its efficacy in non-Veterans recovering from AD. The aim of this study was to extend these findings in an 8-week trial of CBT-I in Veterans. METHODS: Veterans recovering from AD were randomly assigned to 8 weeks of treatment with CBT-I (N = 11) or a Monitor-Only (MO; N = 11) condition and were evaluated 3 (N = 21/22) and 6 months posttreatment (N = 18/22). The primary outcome measure was the Insomnia Severity Index (ISI) score. Secondary outcome measures were sleep diary measures, percent days abstinent (PDA), and scores on the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS), Sleep Hygiene Index (SHI), Penn Alcohol Craving Scale (PACS), Quick Inventory of Depressive Symptoms (QIDS), State-Trait Anxiety Inventory-Trait (STAI-T) scale, and Short Form 12-item (SF-12). Mixed-effects regression models, adjusted for race, evaluated differences in outcomes between the groups over a 6-month period (clinicaltrials.gov identifier = NCT01603381). RESULTS: Subjects were male, aged 54.5 (SD = 6.9) years, and had 26.4 (SD = 26.3) days of abstinence before their baseline evaluation. CBT-I produced a significantly greater improvement in model-based estimates than MO (mean change at 6 months compared to their baseline) for ISI, sleep latency from a daily sleep diary, DBAS mean score, and SHI total score. PDA and QIDS improved over time, but there was no difference between the groups. PACS, STAI-T, or SF-12 scale did not show any improvement from their baseline scores. CONCLUSIONS: CBT-I treatment demonstrated substantial efficacy in reducing insomnia, associated negative cognitions, and improving sleep hygiene in Veterans during early recovery, though it did not reduce drinking behavior.

Performance of prostate cancer recurrence nomograms by obesity status: a retrospective analysis of a radical prostatectomy cohort.

BACKGROUND: Obesity has been associated with aggressive prostate cancer and poor outcomes. It is important to understand how prognostic tools for that guide prostate cancer treatment may be impacted by obesity. The goal of this study was to evaluate the predicting abilities of two prostate cancer (PCa) nomograms by obesity status. METHODS: We examined 1576 radical prostatectomy patients categorized into standard body mass index (BMI) groups. Patients were categorized into low, medium, and high risk groups for the Kattan and CaPSURE/CPDR scores, which are based on PSA value, Gleason score, tumor stage, and other patient data. Time to PCa recurrence was modeled as a function of obesity, risk group, and interactions. RESULTS: As expected for the Kattan score, estimated hazard ratios (95% CI) indicated higher risk of recurrence for medium (HR = 2.99, 95% CI = 2.29, 3.88) and high (HR = 8.84, 95% CI = 5.91, 13.2) risk groups compared to low risk group. The associations were not statistically different across BMI groups. Results were consistent for the CaPSURE/CPDR score. However, the difference in risk of recurrence in the high risk versus low risk groups was larger for normal weight patients than the same estimate in the obese patients. CONCLUSIONS: We observed no statistically significant difference in the association between PCa recurrence and prediction scores across BMI groups. However, our study indicates that there may be a stronger association between high risk status and PCa recurrence among normal weight patients compared to obese patients. This suggests that high risk status based on PCa nomogram scores may be most predictive among normal weight patients. Additional research in this area is needed.

Longitudinal imaging reveals subhippocampal dynamics in glutamate levels associated with histopathologic events in a mouse model of tauopathy and healthy mice.

Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, and traumatic brain injury. Glutamate metabolism is altered in neurodegenerative disorders manifesting in higher or lower concentrations of glutamate, its transporters or receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that glutamate levels are reduced in regions of synapse loss in the hippocampus of a mouse model of late-stage tauopathy. We performed a longitudinal GluCEST imaging experiment paired with a cross-sectional study of histologic markers of tauopathy to determine whether (1) early GluCEST changes are associated with synapse loss before volume loss occurs in the hippocampus, and whether (2) subhippocampal dynamics in GluCEST are associated with histopathologic events related to glutamate alterations in tauopathy. Live imaging of the hippocampus in three serial slices was performed without exogenous contrast agents, and subregions were segmented based on a k-means cluster model. Subregions of the hippocampus were analyzed (cornu ammonis CA1, CA3, dentate gyrus DG, and ventricle) in order to associate local MRI-observable changes in glutamate with histological measures of glial cell proliferation (GFAP), synapse density (synaptophysin, VGlut1) and glutamate receptor (NMDA-NR1) levels. Early differences in GluCEST between healthy and tauopathy mice were measured in the CA1 and DG subregions (30% reduction, P ≤ 0.001). Synapse density was also significantly reduced in every subregion of the hippocampus in tauopathy mice by 6 months. Volume was not significantly reduced in any subregion until 13 months. Further, a gradient in glutamate levels was observed in vivo along hippocampal axes that became polarized as tauopathy progressed. Dynamics in hippocampal glutamate levels throughout lifetime were most closely correlated with combined changes in synaptophysin and GFAP, indicating that GluCEST imaging may be a surrogate marker of glutamate concentration in glial cells and at the synaptic level. © 2016 Wiley Periodicals, Inc.

A health care navigation tool assesses asthma self-management and health literacy.

BACKGROUND: Self-management of moderate-to-severe asthma depends on the patient's ability to (1) navigate (access health care to obtain diagnoses and treatment), (2) use inhaled corticosteroids (ICSs) properly, and (3) understand ICS function. OBJECTIVE: We sought to test whether navigation skills (medication recall, knowledge of copay requirements, and ability to provide information needed for a medical visit about a persistent cough unresponsive to medication) are related to other self-management skills and health literacy. METHODS: A 21-item Navigating Ability (NAV2) questionnaire was developed, validated, and then read to adults with moderate-to-severe asthma. ICS technique was evaluated by using scales derived from instructions in national guidelines; knowledge of ICS function was evaluated by using a validated 10-item questionnaire. Spearman correlation was computed between NAV2 score and these questionnaires and with numeracy (Asthma Numeracy Questionnaire) and print literacy (Short Test of Functional Health Literacy in Adults). RESULTS: Two hundred fifty adults participated: age, 51 ± 13 years; 72% female; 65% African American; 10% Latino; 50% with household income of less than $30,000/y; 47% with no more than a 12th-grade education; and 29% experienced hospitalizations for asthma in the prior year. A higher NAV2 score was associated with correct ICS technique (ρ = 0.24, P = .0002), knowledge of ICSs (ρ = 0.35, P < .001), better print literacy (ρ = 0.44, P < .001), and numeracy (ρ = 0.41, P < .001). CONCLUSIONS: Patients with poor navigational ability are likely to have poor inhaler technique and limited understanding of ICS function, as well as limited numeracy and print literacy. Clinicians should consider these elements of self-management for their effect on asthma care and as a marker of more general health literacy deficits.

Cardiac Arrests Associated With Tracheal Intubations in PICUs: A Multicenter Cohort Study.

OBJECTIVES: To determine the incidence and epidemiologic characteristics of cardiac arrests among tracheal intubations in PICUs. DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Twenty-five diverse PICUs. PATIENTS: Critically ill children requiring tracheal intubation in PICUs. INTERVENTIONS: Tracheal intubation quality improvement data were prospectively collected for all initial tracheal intubations in 25 PICUs from July 2010 to March 2014 using National Emergency Airway Registry for Children registry. MEASUREMENTS AND MAIN RESULTS: Tracheal intubation-associated cardiac arrest was defined as chest compressions more than 1 minute occurring during tracheal intubation or within 20 minutes after tracheal intubation. A total of 5,232 pediatric tracheal intubations were evaluated. Tracheal intubation-associated cardiac arrest was reported in 87 (1.7%). Patient factors (demographics and indications for tracheal intubation), provider factors (discipline and training level), and practice factors (tracheal intubation method and use of neuromuscular blockade) were recorded. Hemodynamic instability and oxygenation failure as tracheal intubation indications were associated with cardiac arrests (adjusted odds ratio, 6.3; 95% CI, 3.9-10.3; and adjusted odds ratio, 4.3; 95% CI, 2.6-6.9, respectively). History of difficult airway and cardiac disease were also associated with cardiac arrests (adjusted odds ratio, 2.1; 95% CI, 1.2-3.5; and adjusted odds ratio, 2.1; 95% CI, 1.2-3.9, respectively). Provider and practice factors were not associated with cardiac arrests, and provider factors did not modify the effect of patient factors on cardiac arrests. CONCLUSIONS: Tracheal intubation-associated cardiac arrests occurred during 1.7% of PICU tracheal intubations. Tracheal intubation-associated cardiac arrests were much more common with tracheal intubations when the child had acute hemodynamic instability or oxygen failure and when the child had a history of difficult airway or cardiac disease.

Multimorbidity, Depression, and Mortality in Primary Care: Randomized Clinical Trial of an Evidence-Based Depression Care Management Program on Mortality Risk.

BACKGROUND: Two-thirds of older adults have two or more medical conditions that often take precedence over depression in primary care. OBJECTIVE: We evaluated whether evidence-based depression care management would improve the long-term mortality risk among older adults with increasing levels of medical comorbidity. DESIGN: Longitudinal analyses of the practice-randomized Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT). Twenty primary care practices randomized to intervention or usual care. PATIENTS: The sample included 1204 older primary care patients completing the Charlson Comorbidity Index (CCI) and other interview questions at baseline. INTERVENTION: For 2 years, a depression care manager worked with primary care physicians to provide algorithm-based care for depression, offering psychotherapy, increasing the antidepressant dose if indicated, and monitoring symptoms, medication adverse effects, and treatment adherence. MAIN MEASURES: Depression status based on clinical interview, CCI to evaluate medical comorbidity, and vital status at 8 years (National Death Index). KEY RESULTS: In the usual care condition, patients with the highest levels of medical comorbidity and depression were at increased risk of mortality over the course of the follow-up compared to depressed patients with minimal medical comorbidity [hazard ratio 3.02 (95% CI, 1.32 to 8.72)]. In contrast, in intervention practices, patients with the highest level of medical comorbidity and depression compared to depressed patients with minimal medical comorbidity were not at significantly increased risk [hazard ratio 1.73 (95% CI, 0.86 to 3.96)]. Nondepressed patients in intervention and usual care practices had similar mortality risk. CONCLUSIONS: Depression management mitigated the combined effect of multimorbidity and depression on mortality. Depression management should be integral to optimal patient care, not a secondary focus.