Application of a Multidisciplinary Model to a Case Example of Presurgical Epilepsy Planning

This article presents a case example which illustrates the multidisciplinary model for presurgical assessment for epilepsy patients. Nearly three million people in the United States are diagnosed with epilepsy and more than one third of this population is refractory to pharmacological treatment. Poor seizure control is associated with additional impairment in quality of life and cognitive and social functioning, and even with premature death. In accordance with these concerns, surgical intervention is increasingly recognized as a viable treatment option, which should be considered soon after drug resistance becomes apparent. Despite the widespread evidence of effectiveness surgery is often delayed, in part because of the necessity, and difficulties, of correctly applying a multidisciplinary approach to presurgical assessment. And yet, a multidisciplinary team is crucial in the evaluation of risks and benefits of possible surgical intervention and in guiding the surgical procedure to maximize seizure control and minimize risk to eloquent cortex. In the model and complex case presented, the neuropsychologist has a critical role in the presurgical evaluation, as well as in the postsurgical evaluation of outcome.     

Association of Intraprocedural Blood Pressure and End Tidal Carbon Dioxide with Outcome After Acute Stroke Intervention

Background

General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association.

Methods

Consecutive patients treated at our institution between August 2007 and December 2010 were identified from a prospective database. Clinical data were then extracted by retrospective chart review. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established prespecified predictors of functional outcome.

Results

Of the 106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased significantly after induction of GA, but there was no association between BP and outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were significantly associated with outcomes in both univariate and multivariate analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale (mRS) 0–3) was higher than in those with unfavorable outcomes (mRS 4–6): 35.2 mmHg versus 32.2 (p = 0.03) at 60 min and 34.9 versus 31.9 (p = 0.04) at 90 min. The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were the same: 0.76 (95 % CI 0.65–0.92; p = 0.004) at 60 min and 0.76 (95 % CI 0.61–0.93; p = 0.01) at 90 min.

Conclusions

While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.     

A Novel System Improves Preservation of Osteochondral Allografts

Background

Osteochondral allografting is an option for successful treatment of large articular cartilage defects. Use of osteochondral allografting is limited by graft availability, often because of loss of chondrocyte viability during storage.

Questions/purposes

The purpose of this study was to compare osteochondral allografts implanted in canine knees after 28 days or 60 days of storage for (1) initial (1 week) safety and feasibility; (2) integrity and positioning with time (12 weeks and 6 months); and (3) gross, cell viability, histologic, biochemical, and biomechanical characteristics at an endpoint of 6 months.

Methods

With Institutional Animal Care and Use Committee approval, adult dogs (n = 16) were implanted with 8-mm cylindrical osteochondral allografts in the lateral and medial femoral condyles of one knee. Osteochondral allografts preserved for 28 or 60 days using either the current tissue bank standard-of-care (SOC) or a novel system (The Missouri Osteochondral Allograft Preservation System, or MOPS) were used, creating four treatment groups: SOC 28-day, MOPS 28-day, SOC 60-day, and MOPS 60-day. Bacteriologic analysis of tissue culture and media were performed. Dogs were assessed by radiographs and arthroscopy at interim times and by gross, cell viability, histology, biochemistry, and biomechanical testing at the 6-month endpoint.

Results

With the numbers available, there was no difference in infection frequency during storage (5% for SOC and 3% for MOPS; p = 0.5). No infected graft was implanted and no infections occurred in vivo. MOPS grafts had greater chondrocyte viability at Day 60 (90% versus 53%; p = 0.002). For 60-day storage, MOPS grafts were as good as or better than SOC grafts with respect to all outcome measures assessed 6 months after implantation.

Conclusions

Donor chondrocyte viability is important for osteochondral allograft success. MOPS allows preservation of chondrocyte viability for up to 60 days at sufficient levels to result in successful outcomes in a canine model of large femoral condylar articular defects.

Clinical Relevance

These findings provide a promising development in osteochondral allograft technology that can benefit the quantity of grafts available for use and the quality of grafts being implanted.     

PEG shielded polymeric double-layered micelles for gene delivery.

A combination of A-B and B-C block copolymers was used to encapsulate DNA inside pEG coated particles, where A is a cationic block (poly(dimethylaminoethyl methacrylate), pDMAEMA) for DNA binding and condensation, B is a hydrophobic block (poly(butylmethacrylate), pBMA) and C is a polyethylene glycol (pEG) block. The AB and BC block copolymers were synthesized by transition metal mediated radical polymerization. The AB block copolymer had a fixed pBMA molecular weight of 3800 g/mol and a varying pDMAEMA molecular weight (from 22 to 65 kg/mol), the BC block copolymer had a fixed composition (pBMA 9000 g/mol; pEG 2000 g/mol). Plasmid DNA containing particles were made via a detergent dialysis method. By this method, particles of approximately 120 nm, as determined by dynamic light scattering (DLS), with a near neutral charge were formed, independent of the DMAEMA block size. DLS measurements and gel electrophoresis indicated that the particles were very stable in cell culture medium at 37 degrees C and resistant to anionic exchange by poly-l-aspartic acid. The particles were able to transfect COS-7 and OVCAR-3 cells with minor toxicity if incubated for 1 or 4 h; incubation for 24 h resulted in an increased toxicity. This paper shows that small polyplexes with near neutral charge can be obtained via a convenient detergent dialysis method using pDMAEMA-b-pBMA and pBMA-b-pEG. These particles may be interesting for in vivo experiments where particles with high positive charges have adverse interactions with blood components.     

Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes

OBJECTIVE: To evaluate the safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: All 95 patients who began insulin pump therapy at Johns Hopkins Hospital between January 1990 and December 2000 were included in the study. The mean age was 12.0 years (range 4-18), and 29% of the patients were <10 years old. Data were obtained by chart review beginning 6-12 months before pump start. The median duration of follow-up was 28 months. RESULTS: There was a small but significant decrease in HbA(1c) at 3-6 months after pump start (7.7 vs. 7.5%; P = 0.03). HbA(1c) levels then gradually increased and remained elevated after 1 year of follow-up; however, this association was confounded by age and diabetes duration, both of which were associated with higher HbA(1c) levels. After adjusting for duration and age, mean HbA(1c) after pump start was significantly lower than before pump start (7.7 vs. 8.1%; P < 0.001). The number of medical complications (diabetic ketoacidosis, emergency department visits) was similar before and after pump start. There were fewer hypoglycemic events after pump start (12 vs. 17, rate ratio 0.46, 95% CI 0.21-1.01). CONCLUSIONS: This study suggests that pump therapy is safe and effective in selected children and adolescents with type 1 diabetes.     

Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening

Summary

We identified that use of VFA may be cost-effective in either selected women from primary care or women attending after a low trauma fracture.

Introduction

Lateral DXA scanning of the spine for vertebral fracture assessment (VFA) is used for research, but its wider role is unclear. We aimed to establish whether VFA is cost-effective in women based on two different scenarios: following a low-trauma fracture, and after screening of high-risk women identified in primary care.

Methods

The fracture cohort (FC) consisted of 377 women and the primary care cohort (PCC) of 251. Vertebral fractures were identified on VFA images by quantitative morphometry (QM). Outcome was cost-effectiveness of VFA, based on predicted change in clinical management defined as the identification of a vertebral fracture in a patient who otherwise falls below the threshold for treatment. FRAX treatment thresholds assessed were (1) 20/3 % thresholds and (2) National Osteoporosis Guidelines Group (NOGG) thresholds.

Results

As a result, 9.8 % from FC and 13.9 % from PCC were identified with vertebral fractures. Management was changed in 21 to 22/377 (5.6–5.8 %) in FC and 12 to 26/251 (4.8–10.4 %) from PCC depending on which thresholds were used. Sensitivity analyses identified medication adherence as the assumption which most influenced the model. The best-estimate cost-per-QALY for use of VFA in FC was £3,243 for 20/3 threshold and £2,130 for NOGG; for PCC, this was £7,831 for 20/3 and was cost-saving for NOGG. Further analyses to adjust for potential false-positive vertebral fracture identification with QM showed VFA was no longer cost-effective.

Conclusion

VFA appears to be cost-effective in routine clinical practise, particularly when relatively inaccurate methods of identification of vertebral fractures are used such as QM.     

Post-Event Processing in Social Anxiety Disorder: Idiosyncratic Priming in the Course of CBT

Post-event processing (PEP) is the cognitive rumination that follows social events for patients with social anxiety. The PEP period was examined in relation to two anxiety provoking tasks in cognitive behavioural group therapy for social anxiety disorder: (1) Attending the first group therapy session (n = 75), and (2) An individually tailored in-session exposure task (n = 50). An assessment of PEP was conducted the week following each task as an indication of the extent of rumination over that event during the subsequent week. Significant PEP occurred after both events, and greater baseline social anxiety predicted greater levels of PEP related to both tasks. Anxiety ratings, as conceptualized by SUDS, were positively correlated with the severity of subsequent PEP related to the exposure task. There was also support for the stability of PEP across the two tasks and for the specificity of the content of PEP as rumination related to social failure, rather than rumination related to depressive symptoms. This study provides additional empirical support for the role of PEP in the cognitive model of social anxiety disorder.