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BACKGROUND: Current guidelines do not recommend routine sentinel node biopsy (SLNB) for ductal carcinoma in situ (DCIS), except in the setting of mastectomy or microinvasive disease. This study aimed to evaluate national SLNB utilization in women undergoing upfront mastectomy for DCIS, identify predictors of SLNB utilization, and determine the percentage with a positive SLNB. METHODS: A retrospective cohort analysis was performed using the NCDB of women with clinical DCIS who underwent upfront mastectomy between 2012 and 2017. Demographic and clinicopathologic variables were compared between patients who underwent SLNB and those who did not. Multivariate logistic regression models were used to identify factors associated with SLNB utilization and positive SLNB. RESULTS: About 38,973 patients met inclusion criteria: 34,231 (88%) underwent SLNB and 4742 (12%) had no surgical axillary staging. Most patients were age 50-69 (51%), non-Hispanic White (71%), with private insurance (66%). On multivariate analysis, older patients were less likely to receive SLNB (P < .01), while patients with higher grade DCIS were more likely to undergo SLNB (P < .01). In those who underwent SLNB (n = 34,231), only 1,149 (3.4%) had nodal involvement. Non-Hispanic Black patients had increased odds of a positive SLNB (P < .01), while those with estrogen receptor positive disease were less likely to be node positive (OR 0.68, P < .001). CONCLUSIONS: While 88% of patients had a SLNB, only 3.4% were found to be node positive. Given this low rate, it is reasonable to consider SLNB omission in select patients with low grade, hormone receptor positive DCIS undergoing upfront mastectomy.
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BACKGROUND: Digital Mental Health (DMH) tools are an effective, readily accessible, and affordable form of mental health support. However, sustained engagement with DMH is suboptimal, with limited research on DMH engagement. The Health Action Process Approach (HAPA) is an empirically supported theory of health behavior adoption and maintenance. Whether this model also explains DMH tool engagement remains unknown. OBJECTIVE: This study examined whether an adapted HAPA model predicted engagement with DMH via a self-guided website. METHODS: Visitors to the Mental Health America (MHA) website were invited to complete a brief survey measuring HAPA constructs. This cross-sectional study tested the adapted HAPA model with data collected using voluntary response sampling from 16,078 sessions (15,619 unique IP addresses from United States residents) on the MHA website from October 2021 through February 2022. Model fit was examined via structural equation modeling in predicting two engagement outcomes: (1) choice to engage with DMH (ie, spending 3 or more seconds on an MHA page, excluding screening pages) and (2) level of engagement (ie, time spent on MHA pages and number of pages visited, both excluding screening pages). RESULTS: Participants chose to engage with the MHA website in 94.3% (15,161/16,078) of the sessions. Perceived need (ß=.66; P<.001), outcome expectancies (ß=.49; P<.001), self-efficacy (ß=.44; P<.001), and perceived risk (ß=.17-.18; P<.001) significantly predicted intention, and intention (ß=.77; P<.001) significantly predicted planning. Planning was not significantly associated with choice to engage (ß=.03; P=.18). Within participants who chose to engage, the association between planning with level of engagement was statistically significant (ß=.12; P<.001). Model fit indices for both engagement outcomes were poor, with the adapted HAPA model accounting for only 0.1% and 1.4% of the variance in choice to engage and level of engagement, respectively. CONCLUSIONS: Our data suggest that the HAPA model did not predict engagement with DMH via a self-guided website. More research is needed to identify appropriate theoretical frameworks and practical strategies (eg, digital design) to optimize DMH tool engagement.
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Internet , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos , Encuestas y Cuestionarios , Salud Mental , Conductas Relacionadas con la SaludRESUMEN
Autonomic dysregulation, including sympathetic hyperactivity, is a common feature of hypertension (HT) and other cardiovascular diseases. The CNS plays a role in driving chronic sympathetic activation in disease, but several lines of evidence suggest that neuroplasticity in the periphery may also contribute. The potential contribution of postganglionic sympathetic neurons to sustained sympathetic hyperactivity is not well understood. We recently discovered that noradrenergic sympathetic neurons in the stellate ganglion (SG) have excitatory cholinergic collateral connections to other neurons within the ganglion. We hypothesize that remodelling of these neurons and increased cholinergic collateral transmission contributes to sustained sympathetic hyperactivity in cardiovascular diseases, including HT. To test that hypothesis, we examined the activity of sympathetic neurons in isolated SG under control conditions and after 1 week of HT induced by peripheral angiotensin II infusion, using whole-cell patch clamp recordings. Despite the absence of central inputs, we observed elevated spontaneous activity and synaptic transmission in sympathetic SG neurons from hypertensive mice that required generation of action potentials. Genetically disrupting cholinergic transmission in noradrenergic neurons decreased basal neuronal activity and prevented angiotensin II-mediated enhancement of activity. Similar changes in activity, driven by increased collateral transmission, were identified in cardiac projecting neurons and neurons projecting to brown adipose tissue. These changes were not driven by altered A-type K+ currents. This suggests that HT stimulates increased activity throughout the intraganglionic network of collateral connections, contributing to the sustained sympathetic hyperactivity characteristic in cardiovascular disease. KEY POINTS: Sympathetic neurons in ganglia isolated from angiotensin II-treated hypertensive mice are more active than neurons from control mice despite the absence of central activation. The enhanced activity is the result of a ganglionic network of cholinergic collaterals, rather than altered intrinsic excitability. Increased neuronal activity was observed in both cardiac neurons and brown adipose tissue-projecting neurons, which are not involved in cardiovascular homeostasis.
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Social determinants of health (SDOH) impact cancer-related health outcomes, including survival, but their impact on symptoms is less understood among the primary brain tumor (PBT) population. We conducted a systematic review to examine the relationships between SDOH and neurocognitive and mood-related symptoms among the PBT population. PubMed, EMBASE, and CINAHL were searched using PROGRESS criteria (place of residence, race/ethnicity, occupation, gender/sex, religion, education, socioeconomic status, and social capital) on March 8th, 2022. Two individuals screened and assessed study quality using the NHLBI Assessment Tool for Observational Cohort and Cross-sectional Studies. Of 3006 abstracts identified, 150 full-text articles were assessed, and 48 were included for a total sample of 28 454 study participants. Twenty-two studies examined 1 SDOH; none examined all 8. Four studies measured place of residence, 2 race/ethnicity, 13 occupation, 42 gender, 1 religion, 18 education, 4 socioeconomic status, and 15 social capital. Fifteen studies assessed neurocognitive and 37 mood-related symptoms. While higher education was associated with less neurocognitive symptoms, and among individuals with meningioma sustained unemployment after surgery was associated with depressive symptoms, results were otherwise disparate among SDOH and symptoms. Most studies were descriptive or exploratory, lacking comprehensive inclusion of SDOH. Standardizing SDOH collection, reducing bias, and recruiting diverse samples are recommended in future interventions.
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Over 80% of adults in the general population experience trauma. Rates of patients with posttraumatic stress disorder (PTSD) are high in primary care settings and are likely to be even higher in federally qualified health centers (FQHCs). Trauma exposure has been linked to psychiatric symptoms and physical health comorbidities, though little research has focused on FQHC patients. This study addresses this by examining clinical and sociodemographic correlates of specific trauma types among FQHC patients. We analyzed secondary data from patients who screened positive for PTSD and were receiving health care in FQHCs in a clinical trial (N = 978). Individuals who did versus did not experience a specific trauma type were compared using between-group tests. In the sample, 91.3% of participants were exposed to a DSM-5 Criterion A traumatic event, with 79.6% experiencing two or more trauma types. Witnessing a life-threatening event (57.3%) and physical assault (55.7%) were the most common traumatic experiences. Physical health comorbidities and worse physical health functioning were associated with a higher likelihood of exposure to all trauma types, with effect sizes larger than PTSD, ds = 0.78-1.35. Depressive and anxiety symptoms were also associated with a higher likelihood of experiencing nearly all trauma types to a lesser magnitude. People of color, OR = 2.45, and individuals experiencing financial inequities, OR = 1.73, had higher odds of experiencing serious accidents as well as other trauma types. The findings highlight the need for trauma-informed care, including routine trauma and PTSD screening, for FQHC patients.
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Background: Organ transplantation from donors with hepatitis C viremia (HCV) to recipients without HCV (HCV D+/R-) has excellent medical outcomes. Less is known about the psychosocial impact and experiences of HCV D+/R- recipients, particularly outside of clinical trials. Methods: We conducted in-depth, semistructured interviews with 24 HCV D+/R- recipients (kidney, n = 8; lung, n = 7; liver, n = 5; heart, n = 3; simultaneous heart and kidney, n = 1) who received transplants outside of clinical trials and were treated for HCV after transplant to assess their experiences and perspectives. We used thematic analysis to analyze the interviews. Results: Interviewees' reasons for accepting an HCV D + organ were based on perceived benefits and confidence in the effectiveness of HCV treatment. The majority (62%) received HCV treatment within 1 month after transplant (range, 1 day-2 months). Most interviewees reported positive transplant outcomes, including reduced wait times and improved survival, health, physical activity, and quality of life. Overall, themes and experiences did not differ significantly between different organ transplant types. Generally, interviewees did not perceive stigma from those aware of the HCV D+ transplant; yet, disclosure was selective and a few recipients reported concerns from family members about posttransplant HCV transmission risk. Other common concerns included treatment costs and delays, which were not always anticipated by recipients. Conclusions: Our findings suggest that HCV D+/R- kidney, liver, and heart and lung transplant recipients outside of clinical trials had overall positive experiences. However, HCV transmission risk, treatments costs, and treatment delays were a source of concern that might be mitigated with targeted pretransplant education.
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BACKGROUND: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC. METHODS: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND. RESULTS: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08). CONCLUSION: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/cirugía , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama/cirugía , Escisión del Ganglio Linfático , Quimioterapia Adyuvante , Axila , Biopsia del Ganglio Linfático Centinela , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patologíaRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). METHODS: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. RESULTS: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). CONCLUSION: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/patología , Terapia Neoadyuvante , Estudios Retrospectivos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Quimioterapia Adyuvante , Capecitabina/uso terapéuticoRESUMEN
The PTSD Checklist for DSM-5 (PCL-5) is a measure of posttraumatic stress disorder (PTSD) symptom severity that is widely used for clinical and research purposes. Although previous work has examined metrics of minimal important difference (MID) of the PCL-5 in veteran samples, no work has identified PCL-5 MID metrics among adults in primary care in the United States. In this secondary analysis, data were evaluated from primary care patients (N = 971) who screened positive for PTSD and participated in a large clinical trial in federally qualified health centers in three U.S. states. Participants primarily self-identified as women (70.2%) and White (70.3%). We calculated test-retest reliability using clinic registry data and multiple distribution- and anchor-based metrics of MID using baseline and follow-up survey data. Test-retest reliability (Pearson's r, Spearman's ρ, intraclass correlation coefficient) ranged from adequate to excellent (.79-.94), with the shortest time lag demonstrating the highest reliability estimate. The MID for the PCL-5 was estimated using multiple approaches. Distribution-based approaches indicated an MID range of 8.5-12.5, and anchor-based approaches indicated an MID range of 9.8-11.7. Taken together, the MID metrics indicate that PCL-5 change scores of 9-12 likely reflect real change in PTSD symptoms and indicate at least an MID for patients, whereas PCL-5 change scores of 5 or less likely are not reliable. These findings can help inform clinicians using the PCL-5 in similar populations to track patient responses to treatment and help researchers interpret PCL-5 score changes in clinical trials.
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Trastornos por Estrés Postraumático , Adulto , Humanos , Femenino , Estados Unidos , Trastornos por Estrés Postraumático/diagnóstico , Lista de Verificación , Reproducibilidad de los Resultados , Psicometría , Atención Primaria de SaludAsunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/diagnóstico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Atención Primaria de Salud , Buprenorfina/uso terapéutico , Tratamiento de Sustitución de OpiáceosRESUMEN
Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT interval in vivo. Constitutive loss of Nos1ap led to genetic background-dependent variable lethality at or right before birth. Heart muscle-restricted Nos1ap knockout, generated using cardiac-specific alpha-myosin heavy chain promoter-driven tamoxifen-inducible Cre, resulted in tissue-level Nos1ap expression reduced by half. This partial loss of expression had no detectable effect on the QT interval or other electrocardiographic and echocardiographic parameters, except for a small but significant reduction in the QRS interval. Given that challenges associated with defining the end of the T wave on murine electrocardiogram can limit identification of subtle effects on the QT interval and that common noncoding NOS1AP variants are also associated with the QRS interval, our findings support the role of NOS1AP in regulation of the cardiac electrical cycle.
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Estudio de Asociación del Genoma Completo , Pez Cebra , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Electrocardiografía , Genotipo , Miocardio , Polimorfismo de Nucleótido Simple , Pez Cebra/genéticaRESUMEN
INTRODUCTION: The "Going Flat" movement became widely publicized in 2016 and provides information and support to women who choose to forego post-mastectomy breast reconstruction (PMBR). The objectives of this study were to evaluate temporal trends in PMBR to ascertain the potential impact of this movement and assess which factors are associated with going flat. METHODS: A retrospective cohort analysis was performed using the NCDB of women with non-metastatic breast cancer who underwent mastectomy between 2004 and 2019. Trends in going flat after mastectomy were examined and stratified by age (< 50, 50-69, ≥ 70). A multivariate logistic regression model was used to identify factors associated with going flat. RESULTS: 650,983 patients met the inclusion criteria: 244,201 (37.5%) underwent PMBR and 406,782 (62.5%) went flat. Among women < 70, rates of going flat steadily decreased from 2004 to 2015 and then stabilized after 2015, coinciding with the rise of the "Going Flat" movement. In multivariate analysis, non-White race, older age, increasing comorbidities, government provided insurance, treatment at a community program, radiotherapy, and adjuvant chemotherapy were associated with a higher likelihood of going flat (p < 0.001). CONCLUSION: In the first 2 years after the "Going Flat" movement, the number of women going flat after mastectomy has stabilized in women < 70 for the first time in over a decade. These trends suggest that the social and cultural impact of this movement may have contributed to the stabilization of PMBR rates.
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Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía , Estudios Retrospectivos , Neoplasias de la Mama/cirugía , Estudios de CohortesAsunto(s)
Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía , Neoplasias de la Mama/cirugíaRESUMEN
This study developed and psychometrically evaluated a brief measure of mental health treatment knowledge (N = 726). Scores from Knowledge about Treatment (KaT) demonstrated a unidimensional measure with good model fit, internal consistency reliability, convergent and predictive validity, test-retest reliability, and measurement invariance across gender, ethnicity, education, and poverty status.
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OBJECTIVE: To retrospectively describe ocular abnormalities reported in dogs with presumed dysautonomia. ANIMALS: 79 dogs with dysautonomia. METHODS: Medical records from the Kansas State University Veterinary Health Center from 2004 to 2021 were reviewed for dogs with a clinical or histopathologic diagnosis of canine dysautonomia (CD). Ophthalmic exam abnormalities, nonocular clinical signs, and outcomes were recorded. RESULTS: Most dogs (73/79 [92.4%]) with CD exhibited at least 1 ocular abnormality. The most common ocular abnormalities were diminished pupillary light reflexes (PLRs) in 55 of 79 (69.6%) dogs and elevation of the third eyelids in 51 of 79 (64.6%) dogs. Schirmer tear test values were bilaterally decreased in 32 of 56 (57.1%) dogs. Other ocular abnormalities included resting mydriasis, ocular discharge, photophobia, blepharospasm, corneal ulceration, and conjunctival vessel pallor. The most common nonocular clinical signs were vomiting or regurgitation in 69 of 79 (87.3%) and diarrhea in 34 of 79 (43.0%) dogs. Pharmacologic testing with dilute 0.01%, 0.05%, or 0.1% pilocarpine yielded pupillary constriction in 42 of 51 (82.4%) dogs. Thirty-two of 79 (40.5%) dogs survived to discharge. Resolution of ocular abnormalities was variable. CLINICAL RELEVANCE: Ophthalmic abnormalities such as diminished PLRs, elevation of the third eyelids, and decreased tear production are commonly associated with CD and provide support for its antemortem clinical diagnosis, though dogs with normal PLRs can be diagnosed with the disease. Pharmacologic testing with dilute topical pilocarpine in dogs with clinical signs suggestive of dysautonomia supports a diagnosis of CD. Ophthalmic abnormalities may improve or resolve over time.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedades de los Perros , Humanos , Perros , Animales , Pilocarpina/farmacología , Membrana Nictitante/patología , Estudios Retrospectivos , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/veterinaria , Vómitos/veterinaria , Conjuntiva/patología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patologíaRESUMEN
Sympathetic nerve loss in the heart predicts the risk of ventricular arrhythmias after myocardial infarction (MI) in patients. Sympathetic denervation after cardiac ischemia-reperfusion is sustained by matrix components chondroitin sulfate proteoglycans (CSPGs) in the cardiac scar. We showed that 4,6-sulfation of CSPGs was critical for preventing nerve growth into the scar. Promoting early reinnervation with therapeutics reduces arrhythmias during the first 2 weeks after MI, but the longer-term consequences of restoring innervation are unknown. Therefore, we asked if the beneficial effects of early reinnervation were sustained. We compared cardiac function and arrhythmia susceptibility 40 days after MI in mice treated on Days 3-10 with vehicle or with intracellular sigma peptide to restore innervation. Surprisingly, both groups had normal innervation density in the cardiac scar 40 days after MI, indicating delayed reinnervation of the infarct in vehicle-treated mice. That coincided with similar cardiac function and arrhythmia susceptibility in the two groups. We investigated the mechanism allowing delayed reinnervation of the cardiac scar. We found that CSPG 4,6-sulfation, which is elevated early after ischemia-reperfusion, was reduced to control levels allowing reinnervation of the infarct. Thus, remodeling of extracellular matrix weeks after injury leads to remodeling of sympathetic neurons in the heart.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Isquemia Miocárdica , Animales , Ratones , Cicatriz , Isquemia , Reperfusión , Proteoglicanos Tipo Condroitín SulfatoRESUMEN
BACKGROUND: Digital mental health interventions, such as 2-way and asynchronous messaging therapy, are a growing part of the mental health care treatment ecosystem, yet little is known about how users engage with these interventions over the course of their treatment journeys. User engagement, or client behaviors and therapeutic relationships that facilitate positive treatment outcomes, is a necessary condition for the effectiveness of any digital treatment. Developing a better understanding of the factors that impact user engagement can impact the overall effectiveness of digital psychotherapy. Mapping the user experience in digital therapy may be facilitated by integrating theories from several fields. Specifically, health science's Health Action Process Approach and human-computer interaction's Lived Informatics Model may be usefully synthesized with relational constructs from psychotherapy process-outcome research to identify the determinants of engagement in digital messaging therapy. OBJECTIVE: This study aims to capture insights into digital therapy users' engagement patterns through a qualitative analysis of focus group sessions. We aimed to synthesize emergent intrapersonal and relational determinants of engagement into an integrative framework of engagement in digital therapy. METHODS: A total of 24 focus group participants were recruited to participate in 1 of 5 synchronous focus group sessions held between October and November 2021. Participant responses were coded by 2 researchers using thematic analysis. RESULTS: Coders identified 10 relevant constructs and 24 subconstructs that can collectively account for users' engagement and experience trajectories in the context of digital therapy. Although users' engagement trajectories in digital therapy varied widely, they were principally informed by intrapsychic factors (eg, self-efficacy and outcome expectancy), interpersonal factors (eg, the therapeutic alliance and its rupture), and external factors (eg, treatment costs and social support). These constructs were organized into a proposed Integrative Engagement Model of Digital Psychotherapy. Notably, every participant in the focus groups indicated that their ability to connect with their therapist was among the most important factors that were considered in continuing or terminating treatment. CONCLUSIONS: Engagement in messaging therapy may be usefully approached through an interdisciplinary lens, linking constructs from health science, human-computer interaction studies, and clinical science in an integrative engagement framework. Taken together, our results suggest that users may not view the digital psychotherapy platform itself as a treatment so much as a means of gaining access to a helping provider, that is, users did not see themselves as engaging with a platform but instead viewed their experience as a healing relationship. The findings of this study suggest that a better understanding of user engagement is crucial for enhancing the effectiveness of digital mental health interventions, and future research should continue to explore the underlying factors that contribute to engagement in digital mental health interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04507360; https://clinicaltrials.gov/ct2/show/NCT04507360.
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CR3 (CD11b/CD18; αmß2 integrin) is a conserved phagocytic receptor. The active conformation of CR3 binds the iC3b fragment of complement C3 as well as many host and microbial ligands, leading to actin-dependent phagocytosis. There are conflicting reports about how CR3 engagement affects the fate of phagocytosed substrates. Using imaging flow cytometry, we confirmed that binding and internalization of iC3b-opsonized polystyrene beads by primary human neutrophils was CR3-dependent. iC3b-opsonized beads did not stimulate neutrophil reactive oxygen species, and most beads were found in primary granule-negative phagosomes. Similarly, Neisseria gonorrhoeae that does not express phase-variable Opa proteins suppresses neutrophil reactive oxygen species and delays phagolysosome formation. Here, binding and internalization of Opa-deleted (Δopa) N. gonorrhoeae by adherent human neutrophils was inhibited using blocking antibodies against CR3 and by adding neutrophil inhibitory factor, which targets the CD11b I-domain. No detectable C3 was deposited on N. gonorrhoeae in the presence of neutrophils alone. Conversely, overexpressing CD11b in HL-60 promyelocytes enhanced Δopa N. gonorrhoeae phagocytosis, which required the CD11b I-domain. Phagocytosis of N. gonorrhoeae was also inhibited in mouse neutrophils that were CD11b-deficient or treated with anti-CD11b. Phorbol ester treatment upregulated surface CR3 on neutrophils in suspension, enabling CR3-dependent phagocytosis of Δopa N. gonorrhoeae. Neutrophils exposed to Δopa N. gonorrhoeae had limited phosphorylation of Erk1/2, p38, and JNK. Neutrophil phagocytosis of unopsonized Mycobacterium smegmatis, which also resides in immature phagosomes, was CR3-dependent and did not elicit reactive oxygen species. We suggest that CR3-mediated phagocytosis is a silent mode of entry into neutrophils, which is appropriated by diverse pathogens to subvert phagocytic killing.
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Neutrófilos , Fagocitosis , Ratones , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antígeno de Macrófago-1/metabolismo , Complemento C3b/metabolismo , Receptores de Complemento/metabolismoRESUMEN
BACKGROUND: Individuals with bipolar disorder commonly present for treatment in primary care settings. Collaborative care and colocated specialty care models can improve quality of care and outcomes, though it is unknown which model is more effective. OBJECTIVE: To compare 12-month treatment outcomes for primary care patients with bipolar disorder randomized to treatment with collaborative care or colocated specialty care. METHODS: We conducted a secondary analysis of 191 patients diagnosed with bipolar disorder treated for 12 months during a comparative effectiveness trial in 12 Federally Qualified Health Centers in three states. Characteristics and outcomes were assessed at enrollment and 12 months. The primary outcome was mental health quality of life scores (Veterans RAND 12-Item Health Survey Mental Health Component Summary), and secondary outcomes included depression and anxiety symptom scores, euthymic mood state, and recovery. T-tests and multiple linear and logistic regression models were used. RESULTS: Among participants (mean age: 40 years; 73% women), the Veterans RAND 12-Item Health Survey Mental Health Component Summary increased in both arms over 12 months (baseline: collaborative care 21.99, SD 10.78; colocated specialty 24.15, SD 12.05; 12-month collaborative care 30.63, SD 13.33; colocated specialty 34.16, SD 12.65). The mean Mental Health Component Summary change did not differ by arm (collaborative care: MΔ = 9.09; colocated specialty: MΔ = 10.73; t = -0.67, P = 0.50). Secondary outcomes also improved at 12 months compared to baseline measured by the Hopkins Symptoms Checklist (MΔ = -0.75; SD = 0.85), Generalized Anxiety Disorder-7 (MΔ = -3.92; SD = 6.48), and Recovery Assessment Scale (MΔ = 0.37; SD = 0.65) and did not differ significantly by arm. The proportion of participants with euthymic mood state increased from 11% to 25% with no statistically significant difference by arm. CONCLUSIONS: The effectiveness of collaborative care and that of colocated specialty care were similar. Both were associated with substantial improvements in mental health quality of life and symptom reduction.