Comprehensive assessment of alcohol-related brain damage (ARBD): gap or chasm in the evidence?

Alcohol-related brain damage (ARBD) is primarily caused by chronic alcohol misuse and thiamine deficiency, and results in a broad range of impairments. Despite the increasing incidence of ARBD in the UK in recent decades, it is currently underdiagnosed, managed inappropriately and treated inadequately. Moreover, information about assessments for individuals with ARBD is currently absent from clinical guidelines and policy documents. The aim of this paper was to review the evidence relating to the neurological, neuropsychological, psychosocial, physical and nutritional assessment of individuals with ARBD to identify appropriate assessment tools that could be used to measure and monitor the impact of ARBD over time. A systematic online database search revealed a total of 160 separate references, 133 of which were rejected and two of which could not be accessed. Twenty-five papers were included in the review, including six neuroimaging studies, 17 neuropsychological studies and two studies using psychosocial methods of assessment. A lack of evidence for nutritional and physical assessment of individuals with ARBD was found. The review findings are inconclusive; most instruments currently used in ARBD research have not specifically been validated for use within an ARBD context. Further research is required to identify comprehensive methods of ARBD assessment.

Centenarians and their hearts: a prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up

Background Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data. Methods We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.5 ± 1.7 years. Electrocardiogram was performed in 103 subjects (87.3%) and echocardiography in 100 (84.7%). All subjects underwent a follow-up for at least 6 months. Results Centenarians with abnormal ECG were less frequently females (72% vs 93%), had higher rates of previous consumption of tobacco (14% vs 0) and alcohol (24% vs 12%), and scored lower in the perception of health status (6.8 ± 2.0 vs 8.3 ± 6.8). Centenarians with significant abnormalities in echocardiography were less frequently able to walk 6 m (33% vs 54%). Atrial fibrillation/flutter was found in 27 subjects (26%). Mean left ventricular (LV) ejection fraction was 60.0 ± 10.5%. Moderate or severe aortic valve stenosis was found in 16%, mitral valve regurgitation in 15%, and aortic valve regurgitation in 13%. Diastolic dysfunction was assessed in 79 subjects and was present in 55 (69.6%). Katz index and LV dilation were independently associated with the ability to walk 6 m. Age, Charlson and Katz indexes, and the presence of significant abnormalities in echocardiography were associated with mortality. Conclusions Centenarians have frequent ECG alterations and abnormalities in echocardiography. More than one fifth has atrial fibrillation, and most have diastolic dysfunction. Left ventricular dilation was associated with the ability to walk 6 m. Significant abnormalities in echocardiography were associated with mortality.

A volumetric approach to risk assessment in mammography: a feasibility study

L. Blot and R. Zwiggelaar, 'A volumetric approach to risk assessment in mammography: a feasibility study', Physics in Medicine and Biology 50 (4), 695-708 (2005)

Isolation, characterization, and functional assessment of novel smooth muscle like stem progenitors

Vascular smooth muscle cells (VSMC) are one of the key players in the pathogenesis of cardiovascular diseases. The origin of neointimal VSMC has thus become a prime focus of research. VSMC originate from multiple progenitors cell types. In embryo the well-defined sources of VSMC include; neural crest cells, proepicardial cells and EPC. In adults, though progenitor cells from bone marrow (BM), circulation and tissues giving rise to SMC have been identified, no progress has been made in terms of isolating highly proliferative clonal population of adult stem cells with potential to differentiate into SMC. Smooth muscle like stem progenitor cells (SMSPC) were isolated from cardiopulmonary bypass filters of adult patients undergoing CABG. Rat SMSPC have previously been isolated by our group from the bone marrow of Fischer rats and also from the peripheral blood of monocrotaline induced pulmonary hypertension (MCT-PHTN) animal model. Characterization of novel SMSPC exhibited stem cell characteristics and machinery for differentiation into SMC. The expression of Isl-1 on SMSPC provided unique molecular identity to these circulating stem progenitor cells. The functional potential of SMSPC was determined by monitoring adoptive transfer of GFP+ SMSPC in rodent models of vascular injury; carotid injury and MCT-PHTN. The participation of SMSPC in vascular pathology was confirmed by quantifying the peripheral blood, and engrafted levels of SMSPC using RT-PCR. In terms of translating into clinical practice, SMSPC could be a good tool for detecting the atherosclerotic plaque burden. The current study demonstrates the existence of novel adult stem progenitor cells in circulation, with the potential role in vascular pathology.

Training in and assessment of the procedural skills required to perform peripheral nerve blockade

The training and ongoing education of medical practitioners has undergone major changes in an incremental fashion over the past 15 years. These changes have been driven by patient safety, educational, economic and legislative/regulatory factors. In the near future, training in procedural skills will undergo a paradigm shift to proficiency based progression with associated requirements for competence-based programmes, valid, reliable assessment tools and simulation technology. Before training begins, the learning outcomes require clear definition; any form of assessment applied should include measurement of these outcomes. Currently training in a procedural skill often takes place on an ad hoc basis. The number of attempts necessary to attain a defined degree of proficiency varies from procedure to procedure. Convincing evidence exists that simulation training helps trainees to acquire skills more efficiently rather than relying on opportunities in their clinical practice. Simulation provides a safe, stress free environment for trainees for skill acquisition, generalization and transfer via deliberate practice. The work described in this thesis contributes to a greater understanding of how medical procedures can be performed more safely and effectively through education. The effect of feedback, provided to novices in a standardized setting on a bench model, based on knowledge of performance was associated with an increase in the speed of skill acquisition and a decrease in error rate during initial learning. The timing of feedback was also associated with effective learning of skill. A marked attrition of skills (independent of the type of feedback provided) was demonstrable 24 hrs after they have first been learned. Using the principles of feedback as described above, when studying the effect of an intense training program on novices of varied years of experience in anaesthesia (i.e. the present training programmes / courses of an intense training day for one or more procedures). There was a marked attrition of skill at 24 hours with a significant correlation with increasing years of experience; there also appeared to be an inverse relationship between years of experience in anaesthesia and performance. The greater the number of years of practice experience, the longer it required a learner to acquire a new skill. The findings of the studies described in this thesis may have important implications for the trainers, trainees and training bodies in the design and implementation of training courses and the formats of delivery of changing curricula. Both curricula and training modalities will need to take account of characteristics of individual learners and the dynamic nature of procedural healthcare.

Optimal assessment of the ability of children with recurrent respiratory tract infections to produce anti-polysaccharide antibodies.

Specific anti-polysaccharide antibody deficiency (SPAD) is an immune disorder. Diagnostic criteria have not yet been defined clearly. One hundred and seventy-six children evaluated for recurrent respiratory tract infections were analysed retrospectively. For each subject, specific anti-pneumococcal antibodies had been measured with two enzyme-linked immunosorbent assays (ELISAs), one overall assay (OA) using the 23-valent pneumococcal polysaccharide vaccine (23-PPSV) as detecting antigen and the other purified pneumococcal polysaccharide serotypes (serotype-specific assay, SSA) (serotypes 14, 19F and 23F). Antibody levels were measured before (n = 176) and after (n = 93) immunization with the 23-PPSV. Before immunization, low titres were found for 138 of 176 patients (78%) with OA, compared to 20 of 176 patients (11%) with the SSA. We found a significant correlation between OA and SSA results. After immunization, 88% (71 of 81) of the patients considered as responders in the OA test were also responders in the SSA; 93% (71 of 76) of the patients classified as responders according to the SSA were also responders in the OA. SPAD was diagnosed in 8% (seven of 93) of patients on the basis of the absence of response in both tests. Thus, we propose to use OA as a screening test for SPAD before 23-PPSV immunization. After immunization, SSA should be used only in case of a low response in OA. Only the absence of or a very low antibody response detected by both tests should be used as a diagnostic criterion for SPAD.

Patient-based outcome assessment instruments in acupuncture research.

BACKGROUND: Outcome assessment can support the therapeutic process by providing a way to track symptoms and functionality over time, providing insights to clinicians and patients, as well as offering a common language to discuss patient behavior/functioning. OBJECTIVES: In this article, we examine the patient-based outcome assessment (PBOA) instruments that have been used to determine outcomes in acupuncture clinical research and highlight measures that are feasible, practical, economical, reliable, valid, and responsive to clinical change. The aims of this review were to assess and identify the commonly available PBOA measures, describe a framework for identifying appropriate sets of measures, and address the challenges associated with these measures and acupuncture. Instruments were evaluated in terms of feasibility, practicality, economy, reliability, validity, and responsiveness to clinical change. METHODS: This study was a systematic review. A total of 582 abstracts were reviewed using PubMed (from inception through April 2009). RESULTS: A total of 582 citations were identified. After screening of title/abstract, 212 articles were excluded. From the remaining 370 citations, 258 manuscripts identified explicit PBOA; 112 abstracts did not include any PBOA. The five most common PBOA instruments identified were the Visual Analog Scale, Symptom Diary, Numerical Pain Rating Scales, SF-36, and depression scales such as the Beck Depression Inventory. CONCLUSIONS: The way a questionnaire or scale is administered can have an effect on the outcome. Also, developing and validating outcome measures can be costly and difficult. Therefore, reviewing the literature on existing measures before creating or modifying PBOA instruments can significantly reduce the burden of developing a new measure.

Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins.

As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra-operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and <15% error in the extraction of optical properties indicating that there is sufficient SNR to leverage the differences in optical properties between negative and close/positive margins. The probe had a sensing depth of 0.5-2.2 mm over the wavelength range of 450-600 nm which is consistent with the pathologic criterion for clear margins of 0-2 mm. There was <1% cross-talk between adjacent channels of the multi-channel probe which shows that multiple sites can be measured simultaneously with negligible cross-talk between adjacent sites. Lastly, the system and measurement procedure were found to be reproducible when evaluated with repeated measures, with a low coefficient of variation (<0.11). The only aspect of the system not optimized for intra-operative use was the imaging time. The manuscript includes a discussion of how the speed of the system can be improved to work within the time constraints of an intra-operative setting.

A randomized clinical trial of a coping improvement group intervention for HIV-infected older adults.

This research tested if a 12-session coping improvement group intervention (n = 104) reduced depressive symptoms in HIV-infected older adults compared to an interpersonal support group intervention (n = 105) and an individual therapy upon request (ITUR) control condition (n = 86). Participants were 295 HIV-infected men and women 50-plus years of age living in New York City, Cincinnati, OH, and Columbus, OH. Using A-CASI assessment methodology, participants provided data on their depressive symptoms using the Geriatric Depression Screening Scale (GDS) at pre-intervention, post-intervention, and 4- and 8-month follow-up. Whether conducted with all participants (N = 295) or only a subset of participants diagnosed with mild, moderate, or severe depressive symptoms (N = 171), mixed models analyses of repeated measures found that both coping improvement and interpersonal support group intervention participants reported fewer depressive symptoms than ITUR controls at post-intervention, 4-month follow-up, and 8-month follow-up. The effect sizes of the differences between the two active interventions and the control group were greater when outcome analyses were limited to those participants with mild, moderate, or severe depressive symptoms. At no assessment period did coping improvement and interpersonal support group intervention participants differ in depressive symptoms.

Computer vision tools for the non-invasive assessment of autism-related behavioral markers

The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated that promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests behavioral markers can be observed late in the first year of life. Many of these studies involved extensive frame-by-frame video observation and analysis of a child's natural behavior. Although non-intrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are impractical for clinical and large population research purposes. Diagnostic measures for ASD are available for infants but are only accurate when used by specialists experienced in early diagnosis. This work is a first milestone in a long-term multidisciplinary project that aims at helping clinicians and general practitioners accomplish this early detection/measurement task automatically. We focus on providing computer vision tools to measure and identify ASD behavioral markers based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure three critical AOSI activities that assess visual attention. We augment these AOSI activities with an additional test that analyzes asymmetrical patterns in unsupported gait. The first set of algorithms involves assessing head motion by tracking facial features, while the gait analysis relies on joint foreground segmentation and 2D body pose estimation in video. We show results that provide insightful knowledge to augment the clinician's behavioral observations obtained from real in-clinic assessments.

In vivo guidance and assessment of liver radio-frequency ablation with acoustic radiation force elastography.

The initial results from clinical trials investigating the utility of acoustic radiation force impulse (ARFI) imaging for use with radio-frequency ablation (RFA) procedures in the liver are presented. To date, data have been collected from 6 RFA procedures in 5 unique patients. Large displacement contrast was observed in ARFI images of both pre-ablation malignancies (mean 7.5 dB, range 5.7-11.9 dB) and post-ablation thermal lesions (mean 6.2 dB, range 5.1-7.5 dB). In general, ARFI images provided superior boundary definition of structures relative to the use of conventional sonography alone. Although further investigations are required, initial results are encouraging and demonstrate the clinical promise of the ARFI method for use in many stages of RFA procedures.

Assessment of toxicity and biodistribution of recombinant AAV8 vector-mediated immunomodulatory gene therapy in mice with Pompe disease.

A preclinical safety study was conducted to evaluate the short- and long-term toxicity of a recombinant adeno-associated virus serotype 8 (AAV2/8) vector that has been developed as an immune-modulatory adjunctive therapy to recombinant human acid α-glucosidase (rhGAA, Myozyme) enzyme replacement treatment (ERT) for patients with Pompe disease (AAV2/8-LSPhGAApA). The AAV2/8-LSPhGAApA vector at 1.6 × 10(13) vector particles/kg, after intravenous injection, did not cause significant short- or long-term toxicity. Recruitment of CD4(+) (but not CD8(+)) lymphocytes to the liver was elevated in the vector-dosed male animals at study day (SD) 15, and in group 8 animals at SD 113, in comparison to their respective control animals. Administration of the vector, either prior to or after the one ERT injection, uniformly prevented the hypersensitivity induced by subsequent ERT in males, but not always in female animals. The vector genome was sustained in all tissues through 16-week postdosing, except for in blood with a similar tissue tropism between males and females. Administration of the vector alone, or combined with the ERT, was effective in producing significantly increased GAA activity and consequently decreased glycogen accumulation in multiple tissues, and the urine biomarker, Glc4, was significantly reduced. The efficacy of the vector (or with ERT) was better in males than in females, as demonstrated both by the number of tissues showing significantly effective responses and the extent of response in a given tissue. Given the lack of toxicity for AAV2/8LSPhGAApA, further consideration of clinical translation is warranted in Pompe disease.

Structured Illumination Microscopy and a Quantitative Image Analysis for the Detection of Positive Margins in a Pre-Clinical Genetically Engineered Mouse Model of Sarcoma.

Intraoperative assessment of surgical margins is critical to ensuring residual tumor does not remain in a patient. Previously, we developed a fluorescence structured illumination microscope (SIM) system with a single-shot field of view (FOV) of 2.1 × 1.6 mm (3.4 mm2) and sub-cellular resolution (4.4 μm). The goal of this study was to test the utility of this technology for the detection of residual disease in a genetically engineered mouse model of sarcoma. Primary soft tissue sarcomas were generated in the hindlimb and after the tumor was surgically removed, the relevant margin was stained with acridine orange (AO), a vital stain that brightly stains cell nuclei and fibrous tissues. The tissues were imaged with the SIM system with the primary goal of visualizing fluorescent features from tumor nuclei. Given the heterogeneity of the background tissue (presence of adipose tissue and muscle), an algorithm known as maximally stable extremal regions (MSER) was optimized and applied to the images to specifically segment nuclear features. A logistic regression model was used to classify a tissue site as positive or negative by calculating area fraction and shape of the segmented features that were present and the resulting receiver operator curve (ROC) was generated by varying the probability threshold. Based on the ROC curves, the model was able to classify tumor and normal tissue with 77% sensitivity and 81% specificity (Youden's index). For an unbiased measure of the model performance, it was applied to a separate validation dataset that resulted in 73% sensitivity and 80% specificity. When this approach was applied to representative whole margins, for a tumor probability threshold of 50%, only 1.2% of all regions from the negative margin exceeded this threshold, while over 14.8% of all regions from the positive margin exceeded this threshold.