Measurement of Developmental and Behavioral Concerns in Toddlers With Tuberous Sclerosis Complex.

BACKGROUND: The TAND (Tuberous Sclerosis Complex [TSC]-Associated Neuropsychiatric Disorders) Checklist was developed as a clinical screener for neurodevelopmental disorders in TSC. Most studies have described patterns in older children and adults. This study sought to better understand behavioral concerns as measured by the TAND Checklist in young children with TSC. METHODS: We examined patterns of caregiver responses to the TAND Checklist in 90 toddlers with TSC (12 to 23 months n = 60; 24 to 36 months n = 30) through data collected during baseline visits across two TSC early intervention studies. RESULTS: Over 90% of caregivers reported at least one behavioral concern related to TAND. The number of concerns increased with age. Delayed language was the most frequently reported concern across ages (12 to 23 months: 58.3%, 24 to 36 months: 86.7%). Questions related to behavioral concerns were largely relevant in this age range, but questions in other areas, such as neuropsychological or academic function, were not. CONCLUSIONS: TAND symptoms are very common in toddlers with TSC, and these symptoms may increase with age. The TAND Checklist is a useful tool for identifying behavioral concerns efficiently, but several items and sections are not suited to younger children. Results support the development of an abbreviated form of the TAND Checklist for toddlers.

The impact of music making on neural efficiency & dual-task walking performance in healthy older adults.

Music making is linked to improved cognition and related neuroanatomical changes in children and adults; however, this has been relatively under-studied in aging. The purpose of this study was to assess neural, cognitive, and physical correlates of music making in aging using a dual-task walking (DTW) paradigm. Study participants (N = 415) were healthy adults aged 65 years or older, including musicians (n = 70) who were identified by current weekly engagement in musical activity. A DTW paradigm consisting of single- and dual-task conditions, as well as portable neuroimaging (functional near-infrared spectroscopy), was administered. Outcome measures included neural activation in the prefrontal cortex assessed across task conditions by recording changes in oxygenated hemoglobin, cognitive performance, and gait velocity. Linear mixed effects models examined the impact of music making on outcome measures in addition to moderating their change between task conditions. Across participants (53.3% women; 76 ± 6.55 years), neural activation increased from single- to dual-task conditions (p < 0.001); however, musicians demonstrated attenuated activation between a single cognitive interference task and dual-task walking (p = 0.014). Musicians also displayed significantly smaller decline in behavioral performance (p < 0.001) from single- to dual-task conditions and faster gait overall (p = 0.014). Given evidence of lower prefrontal cortex activation in the context of similar or improved behavioral performance, results indicate the presence of enhanced neural efficiency in older adult musicians. Furthermore, improved dual-task performance in older adult musicians was observed. Results have important clinical implications for healthy aging, as executive functioning plays an essential role in maintaining functional ability in older adulthood.

Assessing within-task verbal fluency performance: the utility of individual time intervals in predicting incident mild cognitive impairment.

The current study aimed to determine whether word generation performance on individual within-task 20-second time intervals predicted conversion to Mild Cognitive Impairment (MCI) status. Longitudinal data (Mean follow-up=2.95±1.64 years) was collected from cognitively-healthy community-dwelling older adults (N=344; %female=56.1). Performance on letter and semantic fluency tasks was divided into three consecutive within-task 20-second intervals. Incident MCI status (n=50) was determined via established diagnostic case conference. Fully adjusted Cox proportional-hazards regression models revealed that greater word production on semantic fluency across all time intervals significantly predicted a reduced risk of incident MCI [0-20 seconds (HR=0.906, p=0.002), 21-40 seconds (HR=0.904, p=0.02), and 41-60 seconds (HR=0.892, p=0.017)]. Conversely, on letter fluency, greater word production within the 41-60 second time interval only was significantly associated with reduced risk of incident MCI (HR=0.886, p=0.002). Overall, the clinical use of within-interval performance is supported given evidence of predictive sensitivity and ease of administration.

Predicting change in perceived social support in late life: The role of personality and gender.

OBJECTIVES: Perceived social support (PSS) has a uniquely beneficial effect on physical and mental health in older adults, yet relatively little is known about patterns of change in PSS during late life. The purpose of this study was to identify risk factors related to individual-level change in PSS, with a focus on personality (specifically Neuroticism and Extraversion) and gender as primary variables of interest. METHOD: The study sample consisted of 409 community-dwelling, healthy older adults (56.5% female) who were followed annually for up to five years. Personality traits were analyzed independently and as combined Neuroticism-Extraversion quadrants. Linear mixed effect models (LMEM) and Cox proportional hazards regression were used to examine continuous change and incidence of decline in PSS, respectively. Analyses were conducted for the entire sample and in stratified models in order to explore the potential moderating effect of gender. RESULTS: Personality was identified as a significant predictor of PSS change, including personality quadrants and High Neuroticism alone. Stratified models revealed significant gender differences, with High Neuroticism-Low Extraversion and High Neuroticism alone consistently linked to PSS decline in males, while Low Neuroticism-Low Extraversion was linked to PSS decline in females. CONCLUSION: Patterns in LMEM and Cox model results suggest that PSS decline in males is likely associated with High Neuroticism, while PSS decline in females may be associated instead with Low Extraversion. Future clinical implications include earlier identification of individuals who are at risk for decreased social support, and its related impact on health.

Intraindividual variability in verbal fluency performance is moderated by and predictive of mild cognitive impairments.

OBJECTIVE: The current study was designed to achieve 2 primary objectives: (a) determine the moderating effect of mild cognitive impairments (MCI) on intraindividual variability in semantic and letter fluency performance taking into account longitudinal annual assessments; and (b) establish predictive utility for intraindividual variability in semantic and letter fluency performance as a risk factor of incident MCI. METHODS: Participants were community-residing older adults (n = 514; M age = 75.89 ± 6.45; 55.1% female). Sixty participants were diagnosed with MCI at baseline and 50 developed incident MCI during the follow-up. We operationalized intraindividual variability as word generation slopes derived from 3 consecutive time intervals during the standard 1-min administration of both letter and semantic fluency tasks (i.e., 0-20 s, 21-40 s, and 41-60 s). RESULTS: Linear mixed effects models revealed significant within task slope effects for semantic (estimate = -8.350; p < .0001; 95% confidence interval [CI] = -8.604, -8.095) and letter (estimate = -5.068; p < .0001; 95% CI [-5.268, -4.869]) fluency indicating that word generation declined over the course of both tasks. The two-way interactions of MCI × Slope were significant for semantic (estimate = 1.34; p = .001; 95% CI [0.551, 2.126]) and letter (estimate = 0.733; p = .020; 95% CI [0.116, 1.350]) fluency indicating attenuated slopes among MCI participants compared to controls taking into account repeated annual assessments. Cox proportional-hazards models revealed that attenuated word generation slope, at baseline, in semantic (hazard ratio [HR] = 2.063; p = .015; 95% = 1.149 to 3.702) but not letter (HR = 0.704; p = .243; 95% CI [0.391, 1.269]) fluency was associated with increased risk of incident MCI. CONCLUSION: Intraindividual variability in verbal fluency performance has clinical and predictive utility; it can be easily incorporated into testing batteries in clinical and research settings. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Fluconazole attenuates lung injury and mortality in a rat peritonitis model.

OBJECTIVE: Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats. SUBJECTS: Male Wistar rats weighing 225-235 g. DESIGN AND SETTING: Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control. INTERVENTIONS: Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water. MEASUREMENTS AND RESULTS: Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole. CONCLUSION: This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.

Fluconazole improves survival in septic shock: a randomized double-blind prospective study.

OBJECTIVE: To demonstrate whether fluconazole reduces multiple organ failure and mortality in early septic shock (<24 hrs). DESIGN: A prospective randomized double-blind study. SETTING: A medical and surgical adult intensive care unit in a tertiary referral center. PATIENTS: Values were obtained from 71 general adult intensive care unit patients. INTERVENTIONS: During a 2.5-yr period, December 1998-June 2001, 71 patients with septic shock attributed to either nosocomial pneumonia (n = 37) or intra-abdominal sepsis (n = 34) were admitted to our intensive care unit and met the criteria of early septic shock and were entered into this study. All patients were randomized by our clinical pharmacist to receive daily either 200 mg of fluconazole in isotonic saline (fluconazole group = 32) or isotonic saline alone (placebo group = 39) intravenously during the course of their septic shock. MEASUREMENTS AND MAIN RESULTS: All patients were closely monitored with pulmonary artery catheters and parameters to calculate daily organ dysfunction and Acute Physiology and Chronic Health Evaluation II scores. There was a highly significant increase in 30-day survival in the fluconazole-treated patients compared with the placebo patients (78% vs. 46%). However, fluconazole was found to be more effective in patients with septic shock attributed to intra-abdominal sepsis than to nosocomial pneumonia. Increased survival in the intra-abdominal sepsis clinical category was mirrored by a significantly lower number of organ failures in the treated group compared with the placebo group whereas the number of organ failures in the fluconazole group attributed to nosocomial pneumonia were not significantly increased compared with the control group. The septic shock state was considered in all cases to be attributed to bacterial and not to disseminated yeast infection with the exception of one patient in the control group who was admitted with candidemia. The mechanisms by which fluconazole exerts its protective effect against septic shock in patients is far from clear. However, fluconazole has been shown to enhance bactericidal activity of neutrophils and also to inhibit transmigration and adhesion of neutrophils in capillaries of distant organs. CONCLUSIONS: The development of organ failure and mortality in septic shock was significantly reduced by fluconazole given intravenously. The mechanism of action of fluconazole in reducing multiple organ dysfunction in this group of patients may be attributed to the ability of fluconazole to increase recruitment, improve bactericidal activity of neutrophils, and to contain microorganisms locally.

Effects of a simple protocol on infective complications in intensive care unit patients undergoing percutaneous dilatational tracheostomy.

In our intensive care unit we monitored infection in 228 patients who underwent percutaneous dilatational tracheostomy (PDT). In the first phase of the study 128 PDTs were performed during a 33-month period and there were 41 infection complications (nosocomial pneumonia, bacteremia with sepsis, and septic shock) in the perioperative period (immediately prior to and for 5 days after PDT). A significant risk factor among patients with nosocomial pneumonia was empirical administration of inappropriate antibiotics, compared to appropriate antibiotics (34% versus 4%, p < 0.001). In the second phase of the study (a 30-month period), a simple antibiotics protocol was prospectively applied to 100 PDT patients. The protocol virtually eliminated inappropriate antibiotic drug use immediately prior to PDT and contributed to a significant reduction in perioperative infective complications (pre-protocol 32% versus protocol 11%, p < 0.001).