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Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary, beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.
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Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.
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BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Imagen por Resonancia Magnética , Humanos , Femenino , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico por imagen , Anciano , Masculino , Biomarcadores/sangre , Péptidos beta-Amiloides/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Fragmentos de Péptidos/sangre , Sistema Nervioso Autónomo/fisiopatología , Proteína Ácida Fibrilar de la Glía/sangre , Anciano de 80 o más Años , Proteínas de Neurofilamentos/sangre , Enfermedades del Sistema Nervioso Autónomo/sangre , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/etiologíaRESUMEN
Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. BPV metrics were derived from continuous beat-to-beat blood pressure monitoring data. Two sequential 7-minute waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test-retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC= .87 and .82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. Beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained from older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.
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Blood pressure variability (BPV) and arterial stiffness are age-related hemodynamic risk factors for neurodegenerative disease, but it remains unclear whether they exert independent or interactive effects on brain health. When combined with high inter-beat BPV, increased intra-beat BPV indicative of arterial stiffness could convey greater pressure wave fluctuations deeper into the cerebrovasculature, exacerbating neurodegeneration. This interactive effect was studied in older adults using multiple markers of neurodegeneration, including medial temporal lobe (MTL) volume, plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Older adults (N=105) without major neurological or systemic disease were recruited and underwent brain MRI and continuous BP monitoring to quantify inter-beat BPV through systolic average real variability (ARV) and intra-beat variability through arterial stiffness index (ASI). Plasma NfL and GFAP were assessed. The interactive effect of ARV and ASI on MTL atrophy, plasma NfL, and GFAP was studied using hierarchical linear regression. Voxel-based morphometry (VBM) was used to confirm region-of-interest analysis findings. The interaction between higher ARV and higher ASI was significantly associated with left-sided MTL atrophy in both the region-of-interest and false discovery rate-corrected VBM analysis. The interactive effect was also significantly associated with increased plasma NfL, but not GFAP. The interaction between higher ARV and higher ASI is independently associated with increased neurodegenerative markers, including MTL atrophy and plasma NfL, in independently living older adults. Findings could suggest the increased risk for neurodegeneration associated with higher inter-beat BPV may be compounded by increased intra-beat variability due to arterial stiffness.
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Apolipoproteína E4 , Presión Sanguínea , Enfermedades de los Pequeños Vasos Cerebrales , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Enfermedades de los Pequeños Vasos Cerebrales/genética , Femenino , Presión Sanguínea/fisiología , Apolipoproteína E4/genética , Masculino , Persona de Mediana Edad , Anciano , Sistema Nervioso Autónomo/fisiopatología , HeterocigotoRESUMEN
Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer's disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = -.02, 95% CI (-.04, -.008), p =.003] and in APOE4 carriers [B = -.03, 95% CI (-.06, -.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.
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Apolipoproteína E4 , Circulación Cerebrovascular , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Masculino , Femenino , Anciano , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Apolipoproteína E4/genética , Persona de Mediana Edad , Envejecimiento/patología , Envejecimiento/fisiología , Heterocigoto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Encéfalo/irrigación sanguínea , Hipercapnia/fisiopatología , Hipercapnia/diagnóstico por imagen , Riesgo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patologíaRESUMEN
OBJECTIVE: A growing evidence base supports stepped care interventions for the early treatment of posttraumatic stress disorder (PTSD) after physical injury. Few investigations have examined the characteristics of patients who do and do not respond to these interventions. METHOD: This investigation was a secondary analysis that used previously collected data from three randomized clinical trials of stepped care interventions (patient N = 498). The study hypothesized that a subgroup of patients would manifest persistent PTSD symptoms regardless of randomization to intervention or control conditions, and that characteristics present at the time of baseline injury hospitalization could distinguish patients who would develop persistent symptoms from potential treatment responders. Regression analyses identified baseline patient clinical and demographic characteristics that were associated with persistent PTSD symptoms over the 6-months post-injury. Additional analyses identified treatment attributes of intervention patients who were and were not likely to demonstrate persistent symptoms. RESULTS: A substantial subgroup of patients (n = 222, 44.6%) demonstrated persistent PTSD symptoms over time. Greater numbers of pre-injury trauma, pre-injury PTSD symptoms, elevated early post-injury PTSD symptoms, unemployment, and non-White race identified patients with persistent symptoms. Patients with ≥3 of these baseline risk characteristics demonstrated diminished treatment responses when compared to patients with <3 characteristics. Intervention patients with ≥3 risk characteristics were less likely to engage in treatment and required greater amounts of interventionist time. CONCLUSIONS: Injured trauma survivors have readily identifiable characteristics at the time of hospitalization that can distinguish responders to PTSD stepped care interventions versus patients who may be treatment refractory.
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Trastornos por Estrés Postraumático , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos por Estrés Postraumático/terapia , Resultado del Tratamiento , Heridas y Lesiones/terapia , Heridas y Lesiones/psicologíaRESUMEN
INTRODUCTION: Early intervention for patients at risk for Posttraumatic Stress Disorder (PTSD) relies upon the ability to engage and follow trauma-exposed patients. Recent requirements by the American College of Surgeons Committee on Trauma (College) have mandated screening and referral for patients with high levels of risk for the development of PTSD or depression. Investigations that assess factors associated with engaging and following physically injured patients may be essential in assessing outcomes related to screening, intervention, and referral. METHODS: This investigation was a secondary analysis of data collected as part of a United States level I trauma center site randomized clinical trial. All 635 patients were ages ≥18 and had high PTSD symptom levels (i.e., DSM-IV PTSD Checklist score ≥35) at the time of the baseline trauma center admission. Baseline technology use, demographic, and injury characteristics were collected for patients who were followed up with over the course of the year after physical injury. Regression analyses were used to assess the associations between technology use, demographic and injury characteristics, and the attainment of follow-up outcome assessments. RESULTS: Thirty-one percent of participants were missing one or more 3-, 6- or 12-month follow-up outcome assessments. Increased risk of missing one or more outcome assessments was associated with younger age (18-30 versus ≥55 Relative Risks [RR] = 1.78, 95 % Confidence Interval [CI] = 1.09, 2.91), lack of cell phone (RR = 1.32, 95 % CI = 1.01, 1.72), no internet access (RR = 1.47, 95 % CI = 1.01, 2.16), public versus private insurance (RR = 1.47, 95 % CI = 1.12, 1.92), having no chronic medical comorbidities (≥4 versus none, RR = 0.28, 95 % CI = 0.20, 0.39), and worse pre-injury mental health function (RR = 0.99, 95 % CI = 0.98, 0.99). CONCLUSIONS: This multisite investigation suggests that younger and publicly insured and/or uninsured patients with barriers to cell phone and internet access may be particularly vulnerable to lapses in trauma center follow-up. Clinical research informing trauma center-based screening, intervention, and referral procedures could productively explore strategies for patients at risk for not engaging and adhering to follow-up care and outcome assessments.
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Trastornos por Estrés Postraumático , Humanos , Estados Unidos , Trastornos por Estrés Postraumático/epidemiología , Salud Mental , Comorbilidad , Análisis de Regresión , Sobrevivientes/psicologíaRESUMEN
Objectives: No large-scale randomized clinical trial investigations have evaluated the potential differential effectiveness of early interventions for post-traumatic stress disorder (PTSD) among injured patients from racial and ethnic minority backgrounds. The current investigation assessed whether a stepped collaborative care intervention trial conducted at 25 level I trauma centers differentially improved PTSD symptoms for racial and ethnic minority injury survivors. Methods: The investigation was a secondary analysis of a stepped wedge cluster randomized clinical trial. Patients endorsing high levels of distress on the PTSD Checklist (PCL-C) were randomized to enhanced usual care control or intervention conditions. Three hundred and fifty patients of the 635 randomized (55%) were from non-white and/or Hispanic backgrounds. The intervention included care management, cognitive behavioral therapy elements and, psychopharmacology addressing PTSD symptoms. The primary study outcome was PTSD symptoms assessed with the PCL-C at 3, 6, and 12 months postinjury. Mixed model regression analyses compared treatment effects for intervention and control group patients from non-white/Hispanic versus white/non-Hispanic backgrounds. Results: The investigation attained between 75% and 80% 3-month to 12-month follow-up. The intervention, on average, required 122 min (SD=132 min). Mixed model regression analyses revealed significant changes in PCL-C scores for non-white/Hispanic intervention patients at 6 months (adjusted difference -3.72 (95% CI -7.33 to -0.10) Effect Size =0.25, p<0.05) after the injury event. No significant differences were observed for white/non-Hispanic patients at the 6-month time point (adjusted difference -1.29 (95% CI -4.89 to 2.31) ES=0.10, p=ns). Conclusion: In this secondary analysis, a brief stepped collaborative care intervention was associated with greater 6-month reductions in PTSD symptoms for non-white/Hispanic patients when compared with white/non-Hispanic patients. If replicated, these findings could serve to inform future American College of Surgeon Committee on Trauma requirements for screening, intervention, and referral for PTSD and comorbidities. Level of evidence: Level II, secondary analysis of randomized clinical trial data reporting a significant difference. Trial registration number: NCT02655354.
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OBJECTIVE: To identify and refer patients at high risk for the psychological sequelae of traumatic injury, the American College of Surgeons Committee on Trauma now requires that trauma centers have in-place protocols. No investigations have documented reductions in utilization and associated potential cost savings associated with trauma center mental health interventions. BACKGROUND: The investigation was a randomized clinical trial analysis that incorporated novel 5-year emergency department (ED)/inpatient health service utilization follow-up data. METHODS: Patients were randomized to a mental health intervention, targeting the psychological sequelae of traumatic injury (n = 85) versus enhanced usual care control (n = 86) conditions. The intervention included case management that coordinated trauma center-to-community care linkages, psychotropic medication consultation, and psychotherapy elements. Mixed model regression was used to assess intervention and control group utilization differences over time. An economic analysis was also conducted. RESULTS: Over the course of the 5-year intervention, patients demonstrated significant reductions in ED/inpatient utilization when compared with control patients [ F (19,3210) = 2.23, P = 0.009]. Intervention utilization reductions were greatest at 3 to 6 months (intervention 15.5% vs control 26.7%, relative risk = 0.58, 95% CI: 0.34, 1.00) and 12 to 15 months (intervention 16.5% vs control 30.6%, relative risk = 0.54, 95% CI: 0.32, 0.91) postinjury time points. The economic analysis suggested potential intervention cost savings. CONCLUSIONS: Mental health intervention is associated with significant reductions in ED and inpatient utilization, as well as potential cost savings. These findings could be productively integrated into future American College of Surgeons Committee on Trauma policy discussions.
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Salud Mental , Centros Traumatológicos , Humanos , Pacientes Internos , Ahorro de Costo , Servicio de Urgencia en Hospital , Progresión de la EnfermedadRESUMEN
BACKGROUND: Each year in the US, approximately 1.5-2.5 million individuals are so severely injured that they require inpatient hospital admissions. The American College of Surgeons Committee on Trauma (College) now requires that trauma centers have in place protocols to identify and refer hospitalized patients at risk injury psychological sequelae. Literature review revealed no investigations that have identified optimal screening, intervention, and referral procedures in the wake of the College requirement. METHODS: The single-site pragmatic trial investigation will individually randomize 424 patients (212 intervention and 212 control) to a brief stepped care intervention versus College required mental health screening and referral control conditions. Blinded follow-up interviews at 1-, 3-, 6-, and 12-months post-injury will assess the symptoms of PTSD and related comorbidity for all patients. The emergency department information exchange (EDIE) will be used to capture population-level automated emergency department and inpatient utilization data for the intent-to-treat sample. The investigation aims to test the primary hypotheses that intervention patients will demonstrate significant reductions in PTSD symptoms and emergency department/inpatient utilization when compared to control patients. The study incorporates a Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE) implementation process assessment. CONCLUSIONS: The overarching goal of the investigation is to advance the sustainable delivery of high-quality trauma center mental health screening, intervention, and referral procedures for diverse injury survivors. An end-of-study policy summit will harness pragmatic trial data to inform the capacity for US trauma centers to implement high-quality acute care mental health screening, intervention and referral services for diverse injured patient populations. TRIAL REGISTRATION: Clinicaltrials.govNCT05632770.
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Trastornos por Estrés Postraumático , Cirujanos , Humanos , Comorbilidad , Derivación y Consulta , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/epidemiología , Centros Traumatológicos , Estados Unidos , Ensayos Clínicos Pragmáticos como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Over the past two decades, pragmatic and implementation science clinical trial research methods have advanced substantially. Pragmatic and implementation studies have natural areas of overlap, particularly relating to the goal of using clinical trial data to leverage health care system policy changes. Few investigations have addressed pragmatic and implementation science randomized trial methods development while also considering policy impact. METHODS: The investigation used the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) and PRECIS-2-Provider Strategies (PRECIS-2-PS) tools to evaluate the design of two multisite randomized clinical trials that targeted patient-level effectiveness outcomes, provider-level practice changes and health care system policy. Seven raters received PRECIS-2 training and applied the tools in the coding of the two trials. Descriptive statistics were produced for both trials, and PRECIS-2 wheel diagrams were constructed. Interrater agreement was assessed with the Intraclass Correlation (ICC) and Kappa statistics. The Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) qualitative approach was applied to understanding integrative themes derived from the PRECIS-2 ratings and an end-of-study policy summit. RESULTS: The ICCs for the composite ratings across the patient and provider-focused PRECIS-2 domains ranged from 0.77 to 0.87, and the Kappa values ranged from 0.25 to 0.37, reflecting overall fair-to-good interrater agreement for both trials. All four PRECIS-2 wheels were rated more pragmatic than explanatory, with composite mean and median scores ≥ 4. Across trials, the primary intent-to-treat analysis domain was consistently rated most pragmatic (mean = 5.0, SD = 0), while the follow-up/data collection domain was rated most explanatory (mean range = 3.14-3.43, SD range = 0.49-0.69). RAPICE field notes identified themes related to potential PRECIS-2 training improvements, as well as policy themes related to using trial data to inform US trauma care system practice change; the policy themes were not captured by the PRECIS-2 ratings. CONCLUSIONS: The investigation documents that the PRECIS-2 and PRECIS-2-PS can be simultaneously used to feasibly and reliably characterize clinical trials with patient and provider-level targets. The integration of pragmatic and implementation science clinical trial research methods can be furthered by using common metrics such as the PRECIS-2 and PRECIS-2-PS. Future study could focus on clinical trial policy research methods development. TRIAL REGISTRATION: DO-SBIS ClinicalTrials.gov NCT00607620. registered on January 29, 2008. TSOS ClinicalTrials.gov NCT02655354, registered on July 27, 2015.
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Ciencia de la Implementación , Proyectos de Investigación , Humanos , Atención a la Salud , InvestigadoresRESUMEN
BACKGROUND: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH. METHODS: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), comparing clinical outcomes using bivariate analyses. RESULTS: 62 patients were included with median age of 33 [IQR 26-37], 74% females. Group A (9/62) and Group S (53/62) had similar baseline characteristics. Papilledema improvement was higher in Group S at 6 weeks and 6 months (44 vs. 93, p = 0.002 and 44 vs. 92%, p = 0.004), with similar improvements across all symptoms. Group S had higher mean post-procedure venous pressure gradient change (8 vs. 3 mmHg, p = 0.02) and a lower CSF opening pressure at 6 months (23 vs. 36 cmH2O, p < 0.001). VPS rescue rate was higher in Group A (44 vs. 2%, p = 0.001). There was only one procedural complications; a subdural hematoma in Group A. CONCLUSIONS: Primary VSS balloon angioplasty provides a marginal and short-lived improvement of IIH symptoms compared to stenting. These findings suggest a cautious and limited role for short-term rescue angioplasty in poor shunting and stenting candidates with refractory IIH.
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Angioplastia de Balón , Hipertensión Intracraneal , Seudotumor Cerebral , Femenino , Humanos , Masculino , Seudotumor Cerebral/diagnóstico por imagen , Seudotumor Cerebral/cirugía , Constricción Patológica/terapia , Constricción Patológica/complicaciones , Senos Craneales/cirugía , Resultado del Tratamiento , Stents/efectos adversos , Estudios RetrospectivosRESUMEN
Background: Increased blood pressure variability (BPV) is a risk factor for cerebral small vessel disease (CSVD) and neurodegeneration, independent of age and average blood pressure, particularly in apolipoprotein E4 (APOE4) carriers. However, it remains uncertain whether BPV elevation is a cause or a consequence of vascular brain injury, or to what degree injury to the central autonomic network (CAN) may contribute to BPV-associated risk in APOE4 carriers. Methods: Independently living older adults (n=70) with no history of stroke or dementia were recruited from the community and underwent 5 minutes of resting beat-to-beat blood pressure monitoring, genetic testing, and brain MRI. Resting BPV, APOE genotype, CSVD burden on brain MRI, and resting state CAN connectivity by fMRI were analyzed. Causal mediation and moderation analysis evaluated BPV and CAN effects on CSVD in APOE4 carriers (n=37) and non-carriers (n=33). Results: Higher BPV was associated with the presence and extent of CSVD in APOE4 carriers, but not non-carriers, independent of CAN connectivity (B= 18.92, P= .02), and CAN connectivity did not mediate the relationship between BPV and CSVD. In APOE4 carriers, CAN connectivity moderated the relationship between BPV and CSVD, whereby BPV effects on CSVD were greater in those with lower CAN connectivity (B= 36.43, P= .02). Conclusions: Older APOE4 carriers with higher beat-to-beat BPV exhibit more extensive CSVD, independent of average blood pressure, and the strength of CAN connectivity does not mediate these effects. Findings suggest increased BPV is more likely a cause, not a consequence, of CSVD. BPV is more strongly associated with CSVD in APOE4 carriers with lower rsCAN connectivity, suggesting CAN dysfunction and BPV elevation may have synergistic effects on CSVD. Further studies are warranted to understand the interplay between BPV and CAN function in APOE4 carriers.
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BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response. OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients. METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and neuro-ophthalmological outcomes (including optical coherence tomography and Humphrey visual fields) were compared. RESULTS: Among 53 patients, the mean age was 32 years and 70% female with a mean body mass index was 36 kg/m 2 . Baseline characteristics were similar between groups. The mean change in lumbar puncture opening pressure at 6 months poststenting was similar between the 3 groups (≤4, 5-8, and >8 mmHg; 13.4, 12.9, and 12.4 cmH 2 O, P = .47). Papilledema improvement was observed across groups at 6 months (100, 93, and 86, P = .7) as were all clinical symptoms. The mean changes in optical coherence tomography retinal nerve fiber layer (-30, -54, and -104, P = .5) and mean deviation in Humphrey visual fields (60, 64, and 67, P = .5) at 6 weeks were not significantly different. CONCLUSION: Patients with IH with low venous pressure gradient venous sinus stenosis seem to benefit equally from venous stenting compared with their higher gradient counterparts. Re-evaluation of our restrictive criteria for this potentially vision sparing intervention is warranted. Future prospective confirmatory studies are needed.
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Hipertensión Intracraneal , Seudotumor Cerebral , Adulto , Constricción Patológica/cirugía , Senos Craneales/diagnóstico por imagen , Senos Craneales/cirugía , Femenino , Humanos , Presión Intracraneal , Masculino , Seudotumor Cerebral/complicaciones , Seudotumor Cerebral/cirugía , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
OBJECTIVE: Few investigations have comprehensively described methods for assessing and monitoring suicidal ideation in pragmatic clinical trials of mental health services interventions. This investigation's goal was to assess a collaborative care intervention's effectiveness in reducing suicidal ideation and describe suicide monitoring implementation in a nationwide protocol. METHOD: The investigation was a secondary analysis of a stepped wedge cluster randomized trial at 25-Level I trauma centers. Injury survivors (N = 635) were randomized to control (n = 370) and intervention (n = 265) conditions and assessed at baseline hospitalization and follow-up at 3-, 6- and 12-months post-injury. The Patient Health Questionnaire (PHQ-9) item-9 was used to evaluate patients for suicidal ideation. Mixed model regression was used to assess intervention versus control group changes in PHQ-9 item-9 scores over time and associations between baseline characteristics and development of suicidal ideation longitudinally. As part of the study implementation process assessment, suicide outreach call logs were also reviewed. RESULTS: Over 50% of patients endorsed suicidal ideation at ≥1 assessment. Intervention patients relative to control patients demonstrated reductions in endorsements of suicidal ideation that did not achieve statistical significance (F[3,1461] = 0.74, P = .53). The study team completed outreach phone calls, texts or voice messages to 268 patients with PHQ-9 item-9 scores ≥1 (n = 161 control, n = 107 intervention). CONCLUSIONS: Suicide assessment and monitoring can be feasibly implemented in large-scale pragmatic clinical trials. Intervention patients demonstrated less suicidal ideation over time; however, these comparisons did not achieve statistical significance. Intensive pragmatic trial monitoring may mask treatment effects by providing control patients a supportive intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02655354.
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Servicios Médicos de Urgencia , Prevención del Suicidio , Suicidio , Humanos , Ideación Suicida , Suicidio/psicología , SobrevivientesRESUMEN
A rapid ethnographic assessment of delivery of mental health services to patients at a Level I trauma center in a major metropolitan hospital undergoing a COVID-19 surge was conducted to assess the challenges involved in services delivery and to compare the experience of delivering services across time. Study participants were patients and providers who interacted with or otherwise were observed by three clinicians engaged in the delivery of care within the Emergency Department (ED) and Trauma Center at Harborview Medical Center from the COVID-19-related "surge" in April to the end of July 2020. Data were collected and analyzed in accordance with the Rapid Assessment Procedures-Informed Clinical Ethnography (RAPICE) protocol. Community and institutional efforts to control the spread of the coronavirus created several challenges to providing mental health services in an acute care setting during the April surge. Most of these challenges were successfully addressed by standardization of infection control protocols, but new challenges emerged including an increase in expenses for infection control and reduction in clinical revenues due to fewer patients, furloughs of mental health services providers and peer specialists in the ED, services not provided or delayed, increased stress due to fear of furloughs or increased workload of those not furloughed, and increases in patients seen with injuries due to risky behavior, violence, and substance use. These findings illustrate the rapidly shifting nature of the pandemic, its impacts on mental health services, and the mitigation efforts of communities and healthcare systems.
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COVID-19 , Servicios de Salud Mental , Antropología Cultural , Atención a la Salud , Servicio de Urgencia en Hospital , Humanos , Pandemias , SARS-CoV-2 , Centros TraumatológicosRESUMEN
INTRODUCTION: Prior retrospective and case-control studies have shown that the use of general anesthesia (GA) during endovascular therapy (EVT) for acute ischemic stroke with large vessel occlusion (AIS-LVO) was independently associated with poor clinical outcomes compared with cases performed under conscious sedation (CS). Conversely, recent small randomized clinical trials (RCT) demonstrated a trend toward better outcome in cases performed under GA. METHODS: We submitted an online survey to 193 Society of Vascular Interventional Neurology and 78 American Association of Neurological Surgeons and Congress of Neurological Surgeons - Cerebrovascular Section neuroendovascular practitioners. Questions were aimed at understanding the current state of anesthesia practice during EVT, and to determine if there is clinical equipoise for a large multicenter RCT comparing GA versus CS during EVT. RESULTS: Between March and May of 2017, we received 116 (43%) responses. Anesthesiologists were responsible for managing 96% of the GA cases as compared to only 51% of the CS cases (P < 0.0001). Notable 56% of providers reported performing less than a quarter of their cases under GA. Only 7% performed all cases under GA compared with 17% who used solely CS (P = 0.048). More than half of respondents thought a new RCT was necessary, of whom 61% were interested in participating. Among interested responders, 59% were located in centers with 3 or more neurointerventionalists. CONCLUSION: The significant variation among neuroendovascular providers, added with the lack of consensus among recent trials and meta-analyses, demonstrate clinical equipoise for further studies to explore the effects of anesthesia during EVT in AIS-LVO.
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Importance: To date, few multisite investigations have evaluated early interventions for injured patients with posttraumatic stress disorder (PTSD) symptoms. Objective: To simultaneously assess the effectiveness and implementation of a brief stepped collaborative care intervention targeting PTSD and comorbidity. Design, Setting, and Participants: A stepped-wedge cluster randomized clinical trial was conducted at 25 US level I trauma centers. Participants included hospitalized survivors of physical injury who underwent a 2-step evaluation for PTSD symptoms. Patients reporting high levels of distress on the PTSD Checklist (PCL-C) were randomized (N = 635) per the stepped-wedge protocol to enhanced usual care control (n = 370) or intervention (n = 265) conditions. The study was conducted from January 4, 2016, through November 2018. Data analysis was performed from November 4, 2019, to December 8, 2020. Interventions: The Trauma Survivors Outcomes and Support collaborative care intervention included proactive injury case management that assisted patients transitioning from hospital inpatient to outpatient and community settings. The intervention also integrated evidence-based pharmacotherapy and psychotherapeutic elements targeting PTSD symptoms and comorbidity. Main Outcomes and Measures: The primary study outcome was PTSD symptoms assessed with the PCL-C at baseline in the surgical ward and at 3, 6, and 12 months postinjury. Secondary outcomes included depressive symptoms, alcohol use, and physical function. Subgroup analyses examined the effect of baseline risk factors for enduring PTSD and quality of protocol implementation on study outcomes. Primary statistical analyses were conducted using the intent-to-treat sample. Results: A total of 327 men (51.5%) were included in analysis; mean (SD) age was 39.0 (14.2) years. The investigation attained follow-up of 75% to 80% of the participants at 3 to 12 months. The intervention lasted a mean (SD) of 122 (132) minutes. Mixed model regression analyses revealed statistically significant changes in PCL-C scores for intervention patients compared with control patients at 6 months (difference, -2.57; 95% CI, -5.12 to -0.03; effect size, 0.18; P < .05) but not 12 months (difference, -1.27; 95% CI, -4.26 to 1.73; effect size, 0.08; P = .35). Subgroup analyses revealed larger PTSD treatment effects for patients with 3 or more baseline risk factors for enduring PTSD and for patients, including firearm injury survivors, treated at trauma centers with good or excellent protocol implementation. Intervention effects for secondary outcomes did not attain statistical significance. Conclusions and Relevance: A brief stepped collaborative care intervention was associated with significant 6-month but not 12-month PTSD symptom reductions. Greater baseline PTSD risk and good or excellent trauma center protocol implementation were associated with larger PTSD treatment effects. Orchestrated efforts targeting policy and funding should systematically incorporate the study findings into national trauma center requirements and verification criteria. Trial Registration: ClinicalTrials.gov Identifier: NCT02655354.