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Objective: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a profound global impact on individual health and well-being in adults and children. While most fully recover from COVID-19, a relatively large subgroup continues to experience persistent physical, cognitive, and emotional/behavioral symptoms beyond the initial infection period. The World Health Organization has termed this phenomenon "Post-COVID-19 Condition" (PCC), better known as "Long COVID." Due to the cognitive and psychosocial symptoms, neuropsychologists often assess and recommend treatment for individuals with Long COVID. However, guidance for neuropsychologists' involvement in clinical care, policy-making, and research has not yet been developed. The authors of this manuscript convened to address this critical gap and develop guidance for clinical neuropsychologists working with patients presenting with Long COVID. Method: Authors include pediatric and adult neuropsychologists with expertise in Long COVID and behavioral health. All authors have been engaged in clinical and research efforts examining the impact of COVID-19. Authors summarized the literature-to-date pertinent to the neuropsychiatric sequelae of Long COVID and developed guidance for neuropsychologists working with individuals with Long COVID. Conclusions: Research findings regarding neuropsychiatric symptoms associated with Long COVID are mixed and limited by methodological differences. As they practice and conduct research, neuropsychologists should remain mindful of the evolving and tenuous nature of the literature.
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BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. METHODS: RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. DISCUSSION: This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.
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COVID-19 , Ensaios Clínicos Fase II como Assunto , Disfunção Cognitiva , Estudos Multicêntricos como Assunto , SARS-CoV-2 , Humanos , COVID-19/complicações , Disfunção Cognitiva/terapia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/diagnóstico , Estudos Prospectivos , Síndrome de COVID-19 Pós-Aguda , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Transcraniana por Corrente Contínua , Cognição , Resultado do Tratamento , Terapia Cognitivo-Comportamental/métodos , Qualidade de VidaRESUMO
Objectives: To determine rates of previously undetected cognitive impairment among patients with depression in primary care. Methods: Patients ages 55 and older with no documented history of dementia or mild cognitive impairment were recruited from primary care practices in New York City, NY and Chicago, IL (n = 855). Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and depression with the Patient Health Questionnaire-8. Results: The mean age was 66.8 (8.0) years, 45.3% were male, 32.7% Black, and 29.2% Latinx. Cognitive impairment increased with severity of depression: 22.9% in persons with mild depression, 27.4% in moderate depression and 41.8% in severe depression (p = .0002). Severe depression was significantly associated with cognitive impairment in multivariable analysis (standardized ß = -.11, SE = 0.33, p < .0001). Discussion: Depression was strongly associated with previously undetected cognitive impairment. Primary care clinicians should consider screening, or expand their screening, for both conditions.
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Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population. Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.
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BACKGROUND: A number of patients post-coronavirus disease-19 (COVID-19) report cognitive impairment (CI), even months after acute infection. We aimed to assess if COVID-19 is associated with increased incidence of CI in comparison to controls. METHODS: We analyzed data from the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort of patients post-COVID-19 ≥18 years of age and non-infected controls. CI was defined by scores ≥ 1.0 standard deviation below population norms, and was assessed using well-validated measures of attention, working memory, processing speed, executive functioning/cognitive flexibility, language, learning, and memory. Logistic regression models assessed odds for CI in each domain in patients post-COVID-19 vs. controls after adjusting for potential confounders. In exploratory analyses, we assessed odds for CI by site of acute COVID-19 care as a proxy for disease severity. FINDINGS: 417 patients post-COVID-19 and 151 controls (mean age 49 years, 63% female, 21% Black, 17% Latinx) were included. In adjusted analyses, patients were significantly more likely than controls to have CI in executive functioning (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.03 to 4.67), particularly those treated in outpatient (OR: 2.22; 95% CI: 1.02 to 4.82) and inpatient hospital (OR: 3.59; 95% CI: 1.27 to 10.16) settings. There were no significant associations between CI in other domains and history of COVID-19 or site of acute care. INTERPRETATION: Patients post-COVID-19 have greater odds of executive dysfunction, suggesting that focused cognitive screening may be prudent, even in those with mild to moderate disease. Studies should explore the pathophysiology and potential treatments for CI in this population. FUNDING: This work was funded by the Icahn School of Medicine at Mount Sinai.
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COVID-19 , Disfunção Cognitiva , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , COVID-19/complicações , Disfunção Cognitiva/etiologia , Função Executiva/fisiologia , AprendizagemRESUMO
OBJECTIVE: Under-perception of airflow limitation is more common in older adults with asthma and may lead to under-reporting of asthma symptoms. Asthma management self-efficacy is linked with better asthma control and quality of life (QoL). We sought to examine asthma and medication beliefs as a mediator in the relationship between both under-perception and self-efficacy with asthma outcomes. METHODS: This cross-sectional study recruited participants with asthma ≥60 years from hospital-affiliated practices in East Harlem and the Bronx, New York. Perception of airflow limitation was measured for 6 weeks by having participants enter peak expiratory flow (PEF) estimates into an electronic peak flow meter followed by PEF blows. We used validated instruments to assess asthma and medication beliefs, asthma management self-efficacy, asthma control, and QoL. Asthma self-management behaviors (SMB) were quantified by electronic and self-report measures of inhaled corticosteroid (ICS) adherence and observation of inhaler technique. RESULTS: The sample comprised 331 participants (51% Hispanic, 27% Black, 84% female). Beliefs mediated the relationship between greater under-perception and better self-reported asthma control (ß = -0.08, p = .02) and better asthma QoL (ß =0.12, p = .02). Higher self-efficacy was also associated with better reported asthma control (ß = -0.10, p = .006) and better asthma QoL (ß =0.13, p = .01) in this indirect effect through beliefs. Accurate perception of airflow limitation was associated with higher adherence to SMB (ß = 0.29, p = .003). CONCLUSIONS: Less threatening asthma beliefs may be maladaptive in under-perception of airflow limitation by contributing to under-reporting of asthma symptoms, but adaptive in the context of higher self-efficacy and better asthma control.
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Asma , Qualidade de Vida , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Autoeficácia , Asma/tratamento farmacológico , Adesão à Medicação , PercepçãoRESUMO
OBJECTIVE: There has been a call for research examining factors that influence asthma outcomes in older adults because of the notable disparities observed in this age group. Social support and self-efficacy are resources that factor into asthma outcomes. The current study aimed to examine the relationship between these resources (independently and jointly) and asthma control and quality of life. METHODS: Older adults with moderate-severe asthma were recruited from NYC. Data were obtained during in-person interviews via validated measures of social support, asthma self-efficacy, asthma control, and asthma quality of life. Linear regression evaluated self-efficacy in the relationship between social support and asthma outcomes. RESULTS: In a sample of 359 older adults (M = 68.04, 47.9% Hispanic, 26.5% Black, and 25.6% other), social support had an inverse association with asthma control. As social support increased, asthma control decreased (ß = 0.95, t(356) = -3.13, p = .002). Self-efficacy significantly moderated this relationship (ß = 0.01, t(356) = 2.37, p = .018). For individuals with low or moderate asthma self-efficacy, more received social support was associated with worse asthma control (ß = -0.33, t(356) = -4.66, p < .0001; ß = -0.20, t(356) = -3.21, p = .0014, respectively). For individuals with high self-efficacy, no relationship was found between received social support and asthma control (ß = -0.10, t(356)= -1.20, p =.23). For asthma quality of life, higher levels of received social support were associated with worse quality of life (ß = -0.88, t(356) = -2.64, p = .009), but this association was not significantly moderated by self-efficacy (ß = 0.01, t(356) = 1.90, p = .0582). CONCLUSIONS: For older adults with asthma, receiving more social support is associated with worse asthma outcomes, especially for older adults with lower asthma self-efficacy.
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Asma , Humanos , Idoso , Asma/terapia , Autoeficácia , Qualidade de Vida , Apoio Social , Modelos LinearesRESUMO
BACKGROUND: The number of adults in the USA with cognitive impairment is increasing; however, few studies report prevalence rates of undiagnosed cognitive impairment among older adults in primary care. OBJECTIVE: To determine the prevalence of undiagnosed cognitive impairment among adults ages 55 years and older in primary care settings and provide normative data for the Montreal Cognitive Assessment in this context. DESIGN: Single interview, observational study. PARTICIPANTS: English-speaking adults ages 55 years and older without diagnoses of cognitive impairment recruited from primary care practices in New York City, NY, and Chicago, IL (n = 872). MAIN MEASURES: Montreal Cognitive Assessment (MoCA). Undiagnosed cognitive impairment was defined by age and education adjusted z-scores more than 1.0 and 1.5 standard deviations below published norms, corresponding to mild or moderate to severe cognitive impairment, respectively. KEY RESULTS: The mean age was 66.8 (8.0) years, 44.7% were male, 32.9% were Black or African-American, and 29.1% were Latinx. Undiagnosed cognitive impairment was identified in 20.8% of subjects (mild impairment, 10.5%; moderate-severe impairment, 10.3%). Impairment at any level of severity was associated in bivariate analyses with several patient characteristics, most notably for race and ethnicity (White, non-Latinx, 6.9% vs. Black, non-Latinx, 26.8%, Latinx, 28.2%, other race, 21.9%; p < 0.0001), place of birth (US 17.5% vs. non-US 30.7%, p < 0.0001), depression (33.1% vs. no depression, 18.1%; p < 0.0001), and impairment in activities of daily living (≥ 1 ADL impairment, 34.0% vs. no ADL impairment, 18.2%; p < 0.0001). CONCLUSIONS: Undiagnosed cognitive impairment is common among urban dwelling older adults attending primary care practices, and was associated with several patient characteristics, including non-White race and ethnicity and depression. Normative data for the MoCA from this study may serve as a useful resource for studies of similar patient populations.
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Atividades Cotidianas , Disfunção Cognitiva , Humanos , Masculino , Idoso , Feminino , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Testes de Estado Mental e Demência , Atenção Primária à Saúde , Chicago/epidemiologia , Testes NeuropsicológicosAssuntos
Antiasmáticos , Asma , Humanos , Idoso , Projetos Piloto , Asma/tratamento farmacológico , Antiasmáticos/uso terapêutico , Pulmão , PercepçãoRESUMO
BACKGROUND: Post-COVID-19 condition is frequently comprised of persistent cognitive sequela, including deficits in attention and executive functions (EFs), which can act as a barrier for regaining pre-illness functional levels. Goal Management Training (GMT) is a cognitive rehabilitation (CR) intervention for improving attention and EFs that has received empirical support in studies of other patient groups. The present study aims to determine the efficacy of GMT for improving everyday attention and EFs in adults who experience persistent cognitive deficits after COVID-19. METHODS: This study protocol describes an open-label randomized controlled trial comparing the efficacy of GMT to a wait list control condition (WL), for improving persistent (> 2 months) cognitive sequela in post-COVID-19 condition. The study aims to recruit 240 participants aged 18 to 65 years with a history of SARS-CoV-2 infection and perceived attentional and EF difficulties in daily life. Participants will be block randomized (computer-algorithm) to either group-based GMT (n = 120) or WL (n = 120). GMT will be internet-delivered to groups of six participants in six two-hour sessions delivered once a week. The primary outcome will be the Metacognition Index of the Behavior Rating Inventory of Executive Function - Adult Version, a self-report measure assessing everyday EF difficulties, specifically metacognition, at six months post-treatment. Secondary outcomes include performance-based neurocognitive measures, and tertiary outcomes include rating scales of cognition, emotional health, quality of life, and fatigue. CONCLUSION: Study findings could contribute to providing an evidence-based treatment option for symptoms that are frequent and debilitating following a prevalent condition. TRIAL REGISTRATION NUMBER: NCT05494424.
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COVID-19 , Terapia Cognitivo-Comportamental , Adulto , Humanos , Qualidade de Vida , Terapia Cognitivo-Comportamental/métodos , Inquéritos e Questionários , Resultado do Tratamento , SARS-CoV-2 , Cognição , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes.
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BACKGROUND: Comorbid posttraumatic stress disorder (PTSD) is highly prevalent and associated with increased morbidity among World Trade Center (WTC) rescue and recovery workers with asthma. However, the potential behavioral pathways underlying this relationship remain unclear. OBJECTIVE: To evaluate whether PTSD is associated with lower adherence to asthma self-management behaviors among WTC workers with asthma. METHODS: We used data from a prospective cohort of WTC workers with a physician diagnosis of asthma who were prescribed controller medications. Presence of comorbid PTSD was determined based on structured clinical interviews. Asthma self-management behaviors included medication adherence, inhaler technique, use of action plans, and trigger avoidance. We conducted unadjusted and multiple regression analyses to evaluate the association of PTSD with asthma self-management. RESULTS: Overall, 30% of 276 WTC workers with asthma had comorbid PTSD. Posttraumatic stress disorder was associated with worse asthma control and poorer quality of life. However, PTSD was not significantly associated with medication adherence (odds ratio [OR] -0.15; 95% confidence interval [CI] -0.5 to 0.2), inhaler technique (OR -0.12; 95% CI -0.7 to 0.5), use of action plans (OR 0.8; 95% CI 0.4 to 1.8), or trigger avoidance (OR 0.9; 95% CI 0.4 to 1.8). CONCLUSIONS: We did not find significant differences in key asthma self-management behaviors between WTC workers with and without PTSD. These results suggest that other mechanisms, such as differences in symptom perception or inflammatory pathways, may explain the association between PTSD and increased asthma morbidity.
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Asma , Autogestão , Ataques Terroristas de 11 de Setembro , Transtornos de Estresse Pós-Traumáticos , Asma/tratamento farmacológico , Asma/epidemiologia , Humanos , Estudos Prospectivos , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
BACKGROUND: Cognitive impairment (CI) is highly prevalent in elderly asthmatics and is associated with worse asthma self-management (SM) and outcomes. CI may also explain why older adults may under-perceive asthma symptoms. We hypothesized that CI would be associated with low medication adherence and asthma symptom under-perception (ASP). We also hypothesized that ASP would mediate the relationship between CI and medication adherence. METHODS: Participants of this longitudinal cohort study were asthmatics (N = 334) ≥60 years (51% Hispanic, 25% Black). Cognitive measures assessed general cognition, attention, processing speed, executive functioning, memory, and language. Measures of SM were self-reported and electronically measured adherence to controller medications. ASP was assessed for 6 weeks by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter, followed by PEF blows. Participants were blinded to actual PEF values. Percentage of time that participants were in the over-perception zone was calculated as an average. RESULTS: In regression analyses, those with impairments in memory and general cognition had lower odds ratios (OR) for self-reported non-adherence (OR: 0.96, 95% CI 0.93 - 0.98 & OR: 0.90, 95% CI 0.83 - 0.96, respectively). CI was not associated with electronically measured non-adherence or ASP. In structural equation modeling, while CI was associated with adherence (ß = 0.04, SE = 0.021, p = 0.04), ASP did not mediate this relationship. CONCLUSIONS: While results confirmed the importance of cognition in asthma SM, these findings were not linked to ASP. Future analyses are needed to understand the role of confounding factors.
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Antiasmáticos , Asma , Idoso , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/psicologia , Cognição , Humanos , Estudos Longitudinais , Adesão à Medicação , PercepçãoAssuntos
COVID-19/epidemiologia , Cognição , Disfunção Cognitiva/epidemiologia , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Estudos Transversais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
OBJECTIVE: Older adults are at increased risk for depression and poor asthma outcomes. We examined whether depressive symptoms are associated with overperception of airflow obstruction and a pattern of worse asthma control, but not pulmonary function. METHODS: We recruited a cohort of adults with asthma 60 years and older in East Harlem and the Bronx, New York. Baseline measures included the Geriatric Depression Scale, Asthma Control Questionnaire, and Mini Asthma Quality of Life Questionnaire. Spirometry was conducted at baseline to assess pulmonary function. Perception of airflow obstruction was assessed for 6 weeks following baseline by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter followed by PEF blows. Participants were blinded to actual PEF values. The percentage of time that participants were in the overperception zone was calculated as an average. RESULTS: Among the 334 participants (51% Hispanic, 25% Black), depressive symptoms were associated with overperception of airflow obstruction (ß = 0.14, p = .029), worse self-reported asthma control (ß = 0.17, p = .003), and lower asthma-related quality of life (ß = -0.33, p < .001), but not with lung function (ß = -0.01, p = .82). Overperception was also associated with worse self-reported asthma control (ß = 0.14, p = .021), but not lung function (ß = -0.05, p = .41). CONCLUSIONS: Depressive symptoms were associated with greater perceived impairment from asthma, but not pulmonary function. Overperception of asthma symptoms may play a key role in the relationship between depression and asthma outcomes in older adults.
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Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Depressão/epidemiologia , Volume Expiratório Forçado , Humanos , Pulmão , Pico do Fluxo Expiratório , Qualidade de VidaRESUMO
Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.
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Transplante de Fígado , Transplante de Órgãos , Criança , Humanos , Imunossupressores/uso terapêutico , Tacrolimo , TransplantadosRESUMO
BACKGROUND: Substrate-limited fed-batch conditions have the favorable effect of preventing overflow metabolism, catabolite repression, oxygen limitation or inhibition caused by elevated substrate or osmotic concentrations. Due to these favorable effects, fed-batch mode is predominantly used in industrial production processes. In contrast, screening processes are usually performed in microtiter plates operated in batch mode. This leads to a different physiological state of the production organism in early screening and can misguide the selection of potential production strains. To close the gap between screening and production conditions, new techniques to enable fed-batch mode in microtiter plates have been described. One of these systems is the ready-to-use and disposable polymer-based controlled-release fed-batch microtiter plate (fed-batch MTP). In this work, the fed-batch MTP was applied to establish a glucose-limited fed-batch screening procedure for industrially relevant protease producing Bacillus licheniformis strains. RESULTS: To achieve equal initial growth conditions for different clones with the fed-batch MTP, a two-step batch preculture procedure was developed. Based on this preculture procedure, the standard deviation of the protease activity of glucose-limited fed-batch main culture cultivations in the fed-batch MTP was ± 10%. The determination of the number of replicates revealed that a minimum of 6 parallel cultivations were necessary to identify clones with a statistically significant increased or decreased protease activity. The developed glucose-limited fed-batch screening procedure was applied to 13 industrially-relevant clones from two B. licheniformis strain lineages. It was found that 12 out of 13 clones (92%) were classified similarly as in a lab-scale fed-batch fermenter process operated under glucose-limited conditions. When the microtiter plate screening process was performed in batch mode, only 5 out of 13 clones (38%) were classified similarly as in the lab-scale fed-batch fermenter process. CONCLUSION: The glucose-limited fed-batch screening process outperformed the usual batch screening process in terms of the predictability of the clone performance under glucose-limited fed-batch fermenter conditions. These results highlight that the implementation of glucose-limited fed-batch conditions already in microtiter plate scale is crucial to increase the precision of identifying improved protease producing B. licheniformis strains. Hence, the fed-batch MTP represents an efficient high-throughput screening tool that aims at closing the gap between screening and production conditions.
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Bacillus licheniformis/metabolismo , Técnicas de Cultura Celular por Lotes , Reatores Biológicos , Peptídeo Hidrolases/biossíntese , Polímeros/metabolismoRESUMO
OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.
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Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Idoso , Cognição , Feminino , Humanos , SobreviventesRESUMO
BACKGROUND: There is insufficient evidence about the ability of pretransplant psychosocial evaluations to predict posttransplant outcomes. While standardized assessments were developed to increase predictive validity, it is unclear whether the risk scores they yield predict outcomes. We investigated if the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), a scaling approach to those assessments, would have been a superior predictor than the standard psychosocial evaluation. METHODS: In this retrospective study, medical records of 182 adult liver transplant recipients who were at least 1 year posttransplant and prescribed tacrolimus for immunosuppression were analyzed. Regression analyses predicted outcomes of interest, including immunosuppressant nonadherence and biopsy-proven rejection, obtained 1-year posttransplant to time of data collection. Nonadherence was determined using the medication level variability index (MLVI). RESULTS: Approximately 49% of patients had MLVI > 2.5, suggestive of nonadherence, and 15% experienced rejection. SIPAT total score did not predict adherence either using the continuous (P = .70), or dichotimized score, above or below > 2.5 (P = .14), or rejection (P = 0.87). Using a SIPAT threshold (total score > 69) did not predict adherence (p = .16) nor was a superior predictor of the continuous adherence score (P = .45), MLVI > 2.5 (P = .42), or rejection (P = 0.49), than the standard evaluation. CONCLUSION: Our findings suggest that the SIPAT is unable to predict 2 of the most important outcomes in this population, immunosuppressant adherence and rejection. Research efforts should attempt to evaluate the best manner to use psychosocial evaluations.
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Transplante de Fígado , Transplante de Órgãos , Adulto , Rejeição de Enxerto , Humanos , Imunossupressores/uso terapêutico , Adesão à Medicação , Estudos Retrospectivos , TacrolimoRESUMO
Se investiga las actividades EEG normales, fronterizas y anormales en 132 niños "normales" que atendieron regularmente al 2§ y 4§ año de una escuela primaria federal en la Ciudad de México; con el objeto de determinar hasta que punto del EEG convencional pudo proporcionar datos subclínicos en los niños con pobre rendimiento escolar (PRE) y aquellos con una historia clínica patológica (AP) y en los controles (C). Se realizó un análisis comparativo de los signos EEG principales entre 2 grupos principales (PRE y C) y 4 subgrupos (PRE + AP, PRE + NoAP, C + AP, C + NoAP). 1.- Los signos anormales fueron significativamente mas frecuentes en el PRE que en el C; y el Pre + AP que en C + AP. 2.-Los signos normales atípicos consistentes en una actividad alfa de gran amplitud y asimetría inconstante, y los signos normales focales paroxisticos y no paroxisticos se encontraron solamente en los grupos PRE y PRE + AP. 3.- La "ondas de sueño" fronterizas se encontraron solamente en los grupos PRE + APy PRE + NoAP; mientras que los potenciales polifásicos solamente se encontraron en los grupos PRE + APyC + AP. 4.- La respuesta excesiva a la hipertiventilación fue significativamente más frecuente en el grupo C que en el PRE y en el C + No AP que en el PRE + AP