Ambulatory Pain Management in the Pediatric Patient Population.

PURPOSE OF REVIEW: Outpatient surgery in the pediatric population has become increasingly common. However, many patients still experience moderate to severe postoperative pain. A poor understanding of the extent of pain after pediatric ambulatory surgery and the lack of randomized control studies of pain management of the outpatient necessitate this review of scientific evidence and multimodal analgesia. RECENT FINDINGS: A multimodal approach to pain management should be applied to the ambulatory setting to decrease postoperative pain. These include non-pharmacological techniques, multimodal pharmacologics, and neuraxial and peripheral nerve blocks. Postoperative pain management in pediatric ambulatory surgical patients remains suboptimal at most centers due to limited evidence-based approach to postoperative pain control. Pediatric ambulatory pain management requires a multipronged approach to address this inadequacy.

Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease.

Alzheimer's disease is characterized by the histopathological presence of amyloid-ß plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.

Parametric mapping using spectral analysis for 11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects.

PURPOSE: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify 11C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. METHODS: Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent 11C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11C-PBR28 parametric maps. These maps were then compared with regional 11C-PBR28 VT (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18F-Flutemetamol PET. RESULTS: With SA, three component peaks were identified in addition to blood volume. The 11C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of 11C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in 11C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well. CONCLUSIONS: This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of 11C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of 11C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.

A heuristic for the distribution of point counts for random curves over a finite field.

How many rational points are there on a random algebraic curve of large genus g over a given finite field Fq? We propose a heuristic for this question motivated by a (now proven) conjecture of Mumford on the cohomology of moduli spaces of curves; this heuristic suggests a Poisson distribution with mean q+1+1/(q-1). We prove a weaker version of this statement in which g and q tend to infinity, with q much larger than g.

Tau Aggregation Correlates with Amyloid Deposition in Both Mild Cognitive Impairment and Alzheimer's Disease Subjects.

BACKGROUND: Amyloid plaque and tau-containing neurofibrillary tangles are important features of Alzheimer's disease (AD). However, the relationship between these processes is still debated. OBJECTIVE: We aimed to investigate local and distant relationships between tau and amyloid deposition in the cortex in mild cognitive impairment (MCI) and AD using PET imaging. METHODS: Seventy-nine subjects (51 controls, 13 amyloid-positive MCI subjects, and 15 amyloid positive AD subjects) underwent MRI and 18F-flutemetamol PET. All MCI/AD subjects and 8 healthy controls as well as 33 healthy control subjects from the ADNI dataset also had 18F-AV1451 PET. Regional and distant correlations were examined after sampling target-to-cerebellar ratio images. Biological parametric mapping was used to evaluate voxel level correlations locally. RESULTS: We found multiple clusters of voxels with highly significant positive correlations throughout the association cortex in both MCI and AD subjects. CONCLUSION: The multiple clusters of positive correlations indicate that tau and amyloid may interact locally and be involved in disease progression. Our findings suggest that targeting both pathologies may be required.

Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume.

OBJECTIVE: To investigate the influence of microglial activation in the early stages of Alzheimer's disease trajectory, we assessed the relationship between microglial activation and gray matter volume and hippocampal volume in patients with mild cognitive impairment (MCI). METHODS: In this study, 55 participants (37 with early stages of MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate gray matter and hippocampal volumes as well as clinical and neuropsychometric evaluation. [11C]PBR28 VT (volume of distribution) was calculated using arterial input function and Logan graphical analysis. Gray matter volume and hippocampal volumes were calculated from MRI for each participant. Statistical parametric mapping software was used to perform voxel-wise correlations and biological parametric mapping analysis. Amyloid status was assessed using [18F]flutemetamol PET. RESULTS: Higher [11C]PBR28 VT in different cortical areas correlated with higher gray matter volume in both amyloid-positive and -negative MCI. In addition, higher hippocampal volume correlated with higher cortical [11C]PBR28 Logan VT. CONCLUSIONS: In this in vivo study, we have demonstrated that microglial activation quantified using [11C]PBR28 PET was associated with higher gray matter volume and higher hippocampal volume in patients with MCI. This might suggest that microglial activation may not always be associated with neuronal damage, and indeed it may have a beneficial effect in the early stages of the Alzheimer trajectory. While further longitudinal studies are necessary, these findings have significant implications on therapeutic strategies targeting microglial activation.

AWARE-AWAreness during REsuscitation-a prospective study.

BACKGROUND: Cardiac arrest (CA) survivors experience cognitive deficits including post-traumatic stress disorder (PTSD). It is unclear whether these are related to cognitive/mental experiences and awareness during CPR. Despite anecdotal reports the broad range of cognitive/mental experiences and awareness associated with CPR has not been systematically studied. METHODS: The incidence and validity of awareness together with the range, characteristics and themes relating to memories/cognitive processes during CA was investigated through a 4 year multi-center observational study using a three stage quantitative and qualitative interview system. The feasibility of objectively testing the accuracy of claims of visual and auditory awareness was examined using specific tests. The outcome measures were (1) awareness/memories during CA and (2) objective verification of claims of awareness using specific tests. RESULTS: Among 2060 CA events, 140 survivors completed stage 1 interviews, while 101 of 140 patients completed stage 2 interviews. 46% had memories with 7 major cognitive themes: fear; animals/plants; bright light; violence/persecution; deja-vu; family; recalling events post-CA and 9% had NDEs, while 2% described awareness with explicit recall of 'seeing' and 'hearing' actual events related to their resuscitation. One had a verifiable period of conscious awareness during which time cerebral function was not expected. CONCLUSIONS: CA survivors commonly experience a broad range of cognitive themes, with 2% exhibiting full awareness. This supports other recent studies that have indicated consciousness may be present despite clinically undetectable consciousness. This together with fearful experiences may contribute to PTSD and other cognitive deficits post CA.

A review of selected dental literature on evidence-based treatment planning for dental implants: report of the Committee on Research in Fixed Prosthodontics of the Academy of Fixed Prosthodontics.

This literature review summarizes research with the aim of providing dentists with evidence-based guidelines to apply when planning treatment with osseointegrated implants. Peer-reviewed literature published in the English language between 1969 and 2003 was reviewed using Medline and hand searches. Topics reviewed include systemic host factors such as age, gender, various medical conditions, and patient habits, local host factors involving the quantity and quality of bone and soft tissue, presence of present or past infection and occlusion, prosthetic design factors, including the number and arrangement of implants, size and coatings of implants, cantilevers and connections to natural teeth, and methods to improve outcomes of implant treatment in each category. The review demonstrated that there is no systemic factor or habit that is an absolute contraindication to the placement of osseointegrated implants in the adult patient, although cessation of smoking can improve outcome significantly. The most important local patient factor for successful treatment is the quality and quantity of bone available at the implant site. Specific design criteria are provided, including guidelines for spacing of implants, size, materials, occlusion, and fit. Limitations in the current body of knowledge are identified, and directions for future research are suggested.