Catheter ablation of ventricular tachycardia

Opinion statement Most patients with ventricular tachycardia (VT) associated with structural heart disease should receive an implantable cardioverter-defibrillator as initial therapy. Patients with symptomatic recurrences of tachycardia, including those with multiple defibrillator shocks, are considered for ablation. The vigor with which antiarrhythmic drug therapy is pursued as antecedent therapy to ablation depends on patient factors (eg, medical comorbidity, type of heart disease, number and hemodynamic tolerance of tachycardias) and the previous history of antiarrhythmic drug exposure (eg, side effects, inefficacy). In patients with mild left ventricular dysfunction and well-tolerated tachycardia, ablation may be offered as primary definitive therapy in selected individuals. In patients without structural heart disease, ablation is usually offered as primary definitive therapy to highly symptomatic patients, and is strongly recommended for patients with recurrent tachycardia following initial attempts at drug suppression. Optimal outcome of VT ablation depends on the availability of an experienced team and sophisticated facilities to accommodate the technical challenges associated with the broad spectrum of clinical presentations and arrhythmia mechanisms. Historically, major complications have been reported in up to 10% of patients, including death, stroke, cardiac tamponade, complete heart block, and myocardial infarction. In our own experience with VT ablation over the past 10 years, major complications occurred in three (1.8%) of 168 patients with structural heart disease and one (0.7%) of 142 patients without structural heart disease.     

To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data

Systematic reviews and meta-analyses that obtain original research data on individual participants enrolled in trials have been described as the gold standard of review. However, they may take longer and be more resource intensive than other types of review. The authors describe potential advantages and disadvantages of the individual patient data (IPD) approach, including benefits from improved data quality, benefits afforded by the type of analyses that can be done, and advantages in achieving consensus around results and interpretation by an international multidisciplinary team. Disadvantages and barriers relating to resource and expertise, negotiating collaboration, and software requirements are also discussed. At the outset, reviewers should consider the methodological factors likely to influence results in their particular review setting, together with time and resource constraints, so that an active decision can be made about whether to extract data from published reports, collect additional or replacement summary data from trialists, or collect IPD.     

A pesticide surface water mobility index and its relationship with concentrations in agricultural drainage watersheds

An index to benchmark pesticide mobility relevant to surface water runoff and soil erosion (surface water mobility index, or SWMI) was derived based on two key environmental fate parameters: degradation half-life and organic carbon-normalized soil/water sorption coefficient (Koc). Values assigned with the index of each individual compound correlate well with the concentration trend of 13 pesticides monitored in six Lake Erie, USA, tributaries from 1983 to 1991. Regression using a power function of SWMI fits concentration data well at various percentiles in the database for each tributary and all six tributaries combined, with r2 ranging from 0.71 to 0.94 for the concentrations at the 95th percentile. Good agreement was also obtained between SWMI and the time-weighted annual mean concentrations (r2 = 0.67-0.87). Although concentrations at or near peaks tend to be driven by rare hydrological events (intense precipitation immediately after application), SWMI explains the peak concentration data generally well (r2 = 0.53-0.86). The SWMI-concentration relationship was further evaluated with two other pesticide monitoring databases: the U.S. Geological Survey National Water Quality Assessment Program White River Study Unit (1991-1996) at Hazelton, Indiana, USA, and the Syngenta (previously Novartis) Voluntary Monitoring Program with Community Water Systems at the Higginsville City Lake, Missouri, USA (1995-1997). The ability of the proposed SWMI to discriminate pesticide runoff mobility and its correlation with surface water monitoring data can be significant in the development of screening methodologies and data-based models for government agencies and/or practitioners in general facing increasing pressure to assess pesticide occurrence in aquatic environments.     

Glucose monitoring by reverse iontophoresis

Glucose can be extracted through intact skin by electro-osmotic flow (a process called 'reverse iontophoresis') upon the application of a low-level electrical current. Recently we have combined iontophoretic extraction with an in situ glucose sensor in a device called the GlucoWatch biographer. Clinical results with this device show close tracking of blood glucose over a range of 2.2 to 22.2 mmol/l for up to 12 h using a single blood glucose value as calibration. The biographer readings lag behind blood glucose values by an average of 18 min. An analysis of data from 92 diabetic subjects in a controlled clinical setting shows a linear relationship (r=0.88) between GlucoWatch biographer readings and blood glucose. The mean absolute relative difference between the two measurements was 15.6% and more than 96% of the data fell in the (A+B) regions of the Clarke error grid. Similar results have been obtained from subjects using the GlucoWatch biographer in an uncontrolled home environment. The automatic, frequent, and non-invasive measurements obtained with the GlucoWatch biographer provide substantially more information about glucose levels than do the current fingerstick methods. This information can be used for improved decisions about all aspects of diabetes management.     

A comparison of traditional and Rasch cut points for assessing clinically important change in health-related quality of life among patients with asthma

Background Patient-perceived change in health-related quality of life (HRQoL) domains has often been classified using a 15-point patient transition rating scale. However, traditional change levels of trivial ( − 1, 0, or 1), minimal (2, 3 or − 2, − 3), moderate (4, 5 or − 4, − 5) and large (6, 7 or − 6, − 7) on this scale have been arbitrarily defined and originally assumed that change related to an improvement was the same as that for a decline. Objective To compare traditional and Rasch partial credit model-derived cut points and the mean changes for each change categorization when assessing clinically important change in asthma-specific HRQoL. Methods Our sample included 396 asthmatic outpatients who completed bimonthly telephone interviews on the Asthma Quality of Life Questionnaire and transition rating items over 1 year of participation. We employed item response theory in a novel approach to identify cut points on domain-specific HRQoL change data and transition ratings. After determining natural cut points for minimal, moderate, and large differences on the transition rating anchor, we calculated mean changes under change categorizations for both improvements and declines for the two transition rating classification approaches. Results Although traditional and Rasch categorizations for small, moderate, and large changes slightly differed and displayed a lack of symmetry between improvements and declines, nearly all mean changes between classification approaches were comparable. Conclusions In this study, traditional transition rating cut points remain suitable to assess HRQoL clinical significance in outpatients with asthma. An earlier version of this paper was presented at the International Society for Quality of Life Research Symposium, June 29, 2004, in Boston, MA and at the International Society for Quality of Life Annual Meeting, October 20, 2005, in San Francisco, CA.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.